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JARID1B POSITIVE MELANOMA CELLS
Using the H3K4 demethylase JARID1B as biomarker, investigators have characterized a small subpopulation of slow-cycling melanoma cells required for continuous tumor growth.
Source: Roesch A, Cell 2010, 141:583-94.
NUCLEOTIDE EXCISION REPAIR
Melanoma cells retain capacity for nucleotide excision repair (NER), the loss of which probably does not commonly contribute to melanoma progression.
Source: Gaddameedhi S, Cancer Res 2010, 70:4922-30.
MELANOMA DORMANCY
In a mouse melanoma model, Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, reinforcing the theory that immune responses favor dormancy of disseminated tumor cells.
Source: Eyles J, J Clin Invest 2010, 120:2030-9.
MTAP AND INTERFERON
Expression of methylthioadenosine phosphorylase (MTAP) might represent a predictive marker for response to adjuvant interferon therapy in patients with skin melanoma.
Source: Meyer S, Exp Dermatol 2010, 19:e251-7.
TARGETING RAP1 GTPase
Preventing the activation or cycling of the Rap1 GTPase alters adhesion and cytoskeletal dynamics and blocks metastatic melanoma cell extravasation into the lungs.
Source: Freeman SA, Cancer Res 2010, 70:4590-601.
FOLLOW-UP FOR STAGE III MELANOMA
Based on the analysis of retrospective data, investigators suggest new guidelines for the follow up of patients with stage III melanoma.
Source: Romano E, J Clin Oncol 2010, 28:3042-7.
ANTI-BPAG1 AUTO-ANTIBODY
Serum levels of anti-BPAG1 auto-antibodies are higher in melanoma patients than in healthy volunteers and thus are proposed as novel melanoma diagnostic marker.
Source: Shimbo T, PLoS One 2010, 5:e10566.
SHIELDS PROGNOSTIC INDEX
The Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions, is proposed to predict outcome of melanoma patients.
Source: Emmett MS, BMC Cancer 2010, 10:208.
PLK1 INHIBITOR BI-2536
In a phase II trial of polo-like kinase 1 inhibitor BI 2536, no objective tumor response was observed in patients with different types of metastatic cancer, including melanoma.
Source: Schoffski P, Eur J Cancer 2010, 46:2206-15.
TOPOISOMERASE I AMPLIFICATION
Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis.
Source: Ryan D, Pigment Cell Melanoma Res 2010, 23:542-53.
NOVEL SMAC MIMETICS
Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib.
Source: Lecis D, Br J Cancer 2010, 102:1707-16.
CHIMERIC ANTIGEN RECEPTORS (CAR)
Designer T cells with second generation GD3-specific CAR plus systemic interleukin-2 (IL2) can eradicate subcutaneous established GD3+ melanoma in nude mice.
Source: Lo AS, Clin Cancer Res 2010, 16:2769-80.
APREPITANT
The NK-1 receptor is expressed by human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on human melanoma cell lines.
Source: Munoz M, Lab Invest 2010, 90:1259-69.
BEVACIZUMAB + IFNalpha
In a pilot trial, patients with metastatic ocular melanoma were treated with bevacizumab and IFN-alpha, which were well tolerated and showed some clinical activity.
Source: Guenterberg KD, Am J Clin Oncol 2010, Epub ahead of print.
GITR ACTIVATION
Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell (Treg) stability and intra-tumor accumulation.
Source: Cohen AD, PLoS One 2010, 5:e10436.
ETARACIZUMAB
The findings of a pharmacodynamic (phase 0) study using etaracizumab (a monoclonal antibody targeting integrin alpha V beta3) in advanced melanoma have been reported.
Source: Moschos S, J Immunother 2010, 33:316-25.
CD147 SILENCING
Depletion of CD147 (a cell surface receptor for cyclophilin A) sensitizes human malignant melanoma cells to hydrogen peroxide-induced oxidative stress.
Source: Li J, J Dermatol Sci 2010, 58:204-10.
9.2.27PE IMMUNOTOXIN
9.2.27PE (Pseudomonas Exotoxin A) immunotoxin can efficiently cause cell death in malignant melanoma cells independent of their level of resistance to apoptosis and DTIC.
Source: Risberg K, J Immunother 2010, 33:272-8.
TARGETED INTERNAL RADIONUCLIDE THERAPY
Melanin targeting radionuclide therapy with a quinoxaline-derived molecule (ICF01012) has strong anti-tumoral efficacy in pigmented versus unpigmented melanomas.
Source: Bonnet M, Pigment Cell Melanoma Res 2010, Epub ahead of print
NRASQ61R and CRE-RECOMBINASE
Targeted delivery of mutationally activated NRAS (NRASQ61R) and Cre-recombinase to post-natal melanocytes induces melanoma in Ink4a/Arflox/lox mice.
Source: VanBrocklin MW, Pigment Cell Melanoma Res 2010, 23:531-41
microRNA DEREGULATED IN MELANOMA
miRNA-200c is consistently downregulated in melanocytes, melanoma cell lines and patient samples, whereas miRNA-205 and miRNA-23b are markedly reduced only in patient samples. miR-146a and miR-155 are upregulated in all analyzed patients but none of the cell lines.
Source: Philippidou D, Cancer Res 2010, 70:4163-73
131-I-LABELED BENZAMIDE
In a xenograft model, 131-I-labeled benzamide proved to be effective for targeted radiotherapy of human melanoma.
Source: Joyal JL, Cancer Res 2010, 70:4045-53
MIC-1 AND ANGIOGENESIS
Inhibition of macrophage inhibitory cytokine 1 (MIC-1) retards melanoma tumor vascular development, subsequently affecting tumor cell proliferation and apoptosis.
Source: Huh SJ, Am J Pathol 2010, 176:2948-57
3-BROMOPYRUVATE
3-bromopyruvate (BrPA) - an inhibitor of glucose metabolism - selectively kills melanoma cells with low levels of glutathione.
Source: Qin JZ, Biochem Biophys Res Commun 2010, 396:495-500
c-RET AND GDNF
Constitutively activated RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma and glial cell line-derived neurotrophic factor (GDNF)-mediated c-RET kinase activation is associated with melanoma pathogenesis.
Source: Ohshima Y, PLoS One 2010, 5:e10279
IGF1R INHIBITION
Disruption of insulin-like growth factor 1 receptot (IGF1R) signaling increases TRAIL-induced apoptosis in human melanoma cell lines.
Source: Karasic TB, Exp Cell Res 2010, 316:1994-2007
IL-24 AND ERLOTINIB
Interleukin-24 (IL-24) gene transfer sensitizes melanoma cells to erlotinib through modulation of the Apaf-1 and Akt signaling pathways.
Source: Deng WG, Melanoma Res 2010, Epub ahead of print
PROTEIN KINASE C ALPHA
RNA interference (RNAi)-mediated knockdown of protein kinase C-alpha (PKC-alpha) inhibits cell migration in MM-RU human metastatic melanoma cell line.
Source: Byers HR, Melanoma Res 2010, 20:171-8
NITRIC OXIDE SYNTHASE INHIBITION
Targeted inhibition of inducible nitric oxide synthase (iNOS)inhibits growth of human melanoma in vivo and synergizes with chemotherapy.
Source: Sikora AG, Clin Cancer Res 2010, 16:1834-44
CXCL4L1/PF-4var47-70
The COOH-terminal peptide of platelet factor-4 variant (CXCL4L1/PF-4var47-70) strongly inhibits angiogenesis and suppresses B16 melanoma growth in vivo.
Source: Vandercappellen J, Mol Cancer Res 2010, 8:322-34
FOXP3
Intratumoral forkhead box P3-positive regulatory T (Treg) cells predict poor survival in cyclooxygenase-2 (COX2) positive uveal melanoma.
Source: Mougiakakos D, Cancer 2010, 116:2224-33
TRIB2
Human TRIB2 is a repressor of FOXO that contributes to the malignant phenotype of melanoma cells.
Source: Zanella F, Oncogene 2010, 29:2973-82
IPILIMUMAB IMPROVES SURVIVAL
In a phase III RCT, anti-CTLA4 antibody ipilimumab (combined or not with gp100 vacination) significantly improves the survival of patients with advanced melanoma resistant to conventional chemotherapy (as compared to gp100 vaccination).
Source: Hodi FS, N Engl J Med 2010, Epub ahead of print
MELANOMA INITIATING CELLS AND CD271
Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.
Source: Boiko AD, Nature 2010, 466:133-7
RCT OF THYMOSIN ALPHA 1
In a phase III RCT, thymosin increases tumor response rates but not overall survival as compared to DTIC + interferon (IFN) alpha.
Source: Maio M, J Clin Oncol 2010, 28:1780-7
LEPTIN AND MELANOMA GROWTH
The metabolic hormone leptin is a melanoma growth factor: a leptin-based autocrine loop may contribute to the proliferation of melanoma cells.
Source: Ellerhorst JA, Oncol Rep 2010, 23:901-7
IGFBP7 GENE THERAPY
Intratumoral injection of pEGFC1-IGFBP7 inhibits malignant melanoma growth in C57BL/6J mice by inducing apoptosis and downregulating VEGF expression.
Source: Chen RY, Oncol Rep 2010, 23:981-8
B-CELLS AND ANTI-MELANOMA IMMUNITY
B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice.
Source: DiLillo DJ, J Immunol 2010, 184:4006-16
PD-1 BLOCKADE + COMBINED IMMUNOTHERAPY
Blockade of programmed death ligand 1 (PD-1) enhances the therapeutic efficacy of combination immunotherapy against murine melanoma in vivo.
Source: Pilon-Thomas S, J Immunol 2010, 184:3442-9
BIOMARKERS FOR ANTI-ANGIOGENIC THERAPY
Using both a murine model and patient biopsies, investigators suggest that resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in melanoma.
Source: Helfrich I, J Exp Med 2010, 207:491-503
MC1R VARIANTS AND CDKN2A MUTATIONS
In a meta-analysis of the literature, MC1R variants significantly increase the penetrance of CDKN2A mutations in melanoma-prone families.
Source: Fargnoli MC, Eur J Cancer 2010, 46:1413-20
IL-24 PLUS DTIC
In a human in vitro model, the combination of interleukin-24 gene therapy and dacarbazine showed anti-melanoma synergism.
Source: Jiang G, Cancer Lett 2010, Epub ahead of print
CONDITIONAL SURVIVAL ANALYSIS (CSA)
Using the SEER database (n=8,647), investigators found that - 8 years after primary surgery - survival differences between low (T2-3N0M0) and high (T4N0M0 or T2-4N1-3M0) risk melanoma patients are no longer significant.
Source: Rueth NM, Ann Surg Oncol 2010, Epub ahead of print
PLEXIN-B1: MELANOMA SUPPRESSOR GENE ?
Plexin B1 can act as a tumor-suppressor protein in melanoma, in part through suppression of c-MET signaling: however, since it also activates AKT, plexin B1 may function as a tumor promoter in melanomas not driven by c-MET activation.
Source: Stevens L, J Invest Dermatol 2010, Epub ahead of print
PESTICIDES AND MELANOMA RISK
In the Agricultural Health Study cohort of licensed pesticide applicators, some pesticides were significantly associated with increased melanoma risk.
Source: Dennis LK, Environ Health Perspect 2010, Epub ahead of print
MITF-MDEL: NEW MELANOMA BIOMARKER
MITF-Mdel, a novel melanocyte/melanoma-specific isoform (splice variant) of microphthalmia-associated transcription factor-M, is proposed as a candidate biomarker for melanoma.
Source: Wang Y, BMC Med 2010, 8:14
4-METHYLUMBELLIFERONE (4-MU)
4-MU inhibits tumour cell growth and the activation of stromal hyaluronan synthesis by melanoma cell-derived factors.
Source: Edward M, Br J Dermatol 2010, Epub ahead of print
PD1 AND CTLA4 BLOCKADE
PD-1 and CTLA-4 combination blockade expands infiltrating T-cells and reduces regulatory T-cells (Treg) and myeloid suppressor cells within B16 melanoma tumors.
Source: Curran MA, Proc Natl Acad Sci USA 2010, 107:4275-80
ETV1: NEW MELANOMA ONCOGENE
ETV1 in combination with oncogenic NRAS(G12D) transformed primary melanocytes (which was dependent on MITF overexpression) and promoted tumor formation in mice.
Source: Jané-Valbuena J, Cancer Res 2010, 70:2075-84
IGFBP7 GENE THERAPY
In vivo transfection of pcDNA3.1-IGFBP7 inhibits melanoma growth in mice through apoptosis induction and VEGF downregulation.
Source: Chen RY, J Exp Clin Cancer Res 2010, 29:13
SELENIUM ANTI-MELANOMA ACTIVITY
In a mouse model, selenium inhibits melanoma metastasis through the induction of cell cycle arrest and cell death.
Source: Song H, Immune Netw 2009, 9:236-42
OCCULT NODAL METASTASIS
In a large series of patients with thin melanoma (n=1732), a scoring system and nomogram for the risk of nodal involvement was created using 3 variables: sex, age and Breslow tumor thickness.
Source: Faries MB, Arch Surg 2010, 145:137-42
CD4+ CYTOTOXIC T-CELLS
Tumor-reactive CD4(+) T-cells - especially in association with anti-CTLA4 antibody - develop cytotoxic activity and eradicate large established syngeneic melanoma after transfer into lymphopenic hosts.
Source: Quezada SA, J Exp Med 2010, 207:637-50
TRICHOSTATIN PLUS 5-AZA
Histone deacetylase inhibitor (HDACI) trichostatin A (TSA) and the DNA methyltransferase inhibitor (DNMTI) 5-azacytidine (5-AZA) show synergistic anti-melanoma activity in vitro.
Source: Essa S, J Steroid Biochem Mol Biol 2010, Epub ahead of print
S100B SERUM LEVELS
Elevated serum levels of protein S100B during the follow-up of patients with melanoma (n=46) showed a low positive predictive value (50%) for disease recurrence.
Source: Aukema TS, Ann Surg Oncol 2010, Epub ahead of print
NEW PROBE FOR PET
In a preclinical in vivo model, (18)F-MEL050 - a melanin selective compound - showed to perform better than standard (18)F-FDG as a PET probe.
Source: Denoyer D, J Nucl Med 2010, 51:441-7
IMIDAZOLE DERIVATIVE 7A
In a human in vitro model, pyrimidin-4-yl-1H-imidazole derivative 7a showed greater anti-melanoma activity than sorafenib and turned out to be a strong CRAF inhibitor.
Source: Lee J, Bioorg Med Chem Lett 2010, 20:1573-7
PLX4032: BRAF V600E SELECTIVE INHIBITOR
PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells.
Source: Halaban R, Pigment Cell Melanoma Res 2010, 23:190-200
NOW AVAILABLE: TARGETED THERAPY DATABASE
The MMMP website now hosts a new database coupled with an original model to match the patient's molecular profile with the available evidence on melanoma targeted therapy (drug ranking system).
Source: MMMP_Targeted Therapy Database
FIRST HUMAN EXPERIENCE OF siRNA + TARGETED NANOPARTICLES
The first phase I clinical trial involving the systemic administration of small interfering RNA (siRNA) to patients with solid cancers using targeted nanoparticles is ongoing. Evidence of inducing RNA intereference in a patient with melanoma has been provided.
Source: Davis ME, Nature 2010, Epub ahead of print
RESPONSE TO IPILIMUMAB
In a multicenter single-arm phase II trial of ipilimumab (monotherapy) for pretreated advanced melanoma (n=155), the best overall response rate was 5.8% and the disease control rate was 27%.
Source: O'Day SJ, Ann Oncol 2010, Epub ahead of print
GENOME-WIDE METHYLATION PROFILING
Genome-wide methylation and expression profiling identifies promoter characteristics affecting demethylation-induced gene upregulation in melanoma.
Source: Rubinstein JC, BMC Med Genomics 2010, 3:4
PD1 LIGAND AND PROGNOSIS
Tumor cell expression of programmed cell death-1 (PD1) ligand is an independent prognostic factor for patients with melanoma (n=59).
Source: Hino R, Cancer 2010, 116:1757-66
IPILIMUMAB AND LYMPHOCYTE COUNT
Absolute lymphocyte count determined in the peripheral blood after 2 cycles of ipilimumab correlates with improved survival of patients with advanced melanoma (n=53).
Source: Ku GY, Cancer 2010, 116:1767-75
POPULATION ATTRIBUTABLE FRACTION (PAF)-2
In a meta-analysis of 66 studies, the PAF for people with skin phototypes I/II, presence of freckling and blond hair color were 27%, 23% and 23%, respectively.
Source: Olsen CM, Int J Cancer 2010, Epub ahead of print
IFN-GAMMA + GGTI298
Human melanoma cells treated with IFN-gamma and geranylgeranyl transferase inhibitor GGTI-298 enhance generation and activity of melanoma-specific cytotoxic T cells.
Source: Sarrabayrouse G, PLoS One 2010, 5:e9043
SLN STATUS "S" CLASSIFICATION
The "S" classification of the SLN status accurately predicts the status of non-sentinel nodes in a series of 365 patients.
Source: Younan R, Ann Surg Oncol 2010, Epub ahead of print
RIBOSOME INHIBITING PROTEIN (RIP)
In a xenograft model, single chain RIP (derived from Shiga like toxin, SLT) synergically increases the therapeutic potential of DTIC.
Source: Cheung MC, Mol Cancer 2010, 9:28
INTEGRIN ALPHA 4
In a murine model, expression of integrin alpha 4 (ligand for endothelial VCAM1) correlates with lymph node metastasis rate.
Source: Rebhun RB, Neoplasia 2010, 12:173-82
PACLITAXEL + CELECOXIB
In a phase II trial (n=20), metronomic paclitaxel + celecoxib (COX2 inhibitor) yielded one partial response and three disease stabilizations.
Source: Bhatt RS, Cancer 2010, 116:1751-6
RCT OF ETARACIZUMAB
In a phase II RCT, dacarbazine does not add significant therapeutic benefit to etaracizumab (a monoclonal antibody against integrin alpha V beta 3.
Source: Hersey P, Cancer 2010, 116:1526-1534
SNB IN 1-2 MM THICK MELANOMA
In a large series of patients (n=1110), sentinel node metastasis was found in 133 cases (12%) and sentinel node status independently predicted survival.
Source: Mays MP, Cancer 2010, 116:1535-44
INTERLEUKIN-29 (IL-29)
IL-29 (interferon lambda 1) binds to melanoma cells inducing Jak-STAT signal transduction and apoptosis.
Source: Guenterberg KD, Mol Cancer Ther 2010, 9:510-20
SPARC SILENCING
In a xenograft model, SPARC silencing shows therapeutic effects against human melanoma.
Source: Horie K, Cancer Sci 2009, Epub ahead of print
IXABEPILONE PHASE II TRIAL
This epotilone B analogue has no therapeutic activity in patients (n=23) with metastatic melanoma.
Source: Ott PA, PLoS One 2010, 5:e8714
MMP-19 AND INVASIVENESS
Matrix metalloproteinase 19 (MMP-19) is upregulated during melanoma progression and increases invasion of human melanoma cells in vitro.
Source: Muller M, Mod Pathol 2010, Epub ahead of print
BEVACIZUMAB FOR OCULAR MELANOMA
In a xenograft model of uveal melanoma, the anti-VEGF antibody bevacizumab suppressed hepatic micrometastasis.
Source: Yang H, Invest Ophthalmol Vis Sci 2010, Epub ahead of print
SLN TUMOR BURDEN
In a series of 381 patients who underwent SLN biopsy, patients with SLN metastatic deposits less or =0.2 mm had no additional positive non-SLN and no recurrences or deaths were recorded.
Source: Francischetto T, Ann Surg Oncol 2010, 17:1152-8
DIAGNOSTIC HELP FROM FISH
Fluorescence in situ hybridization (FISH) is a useful adjunct tool to traditional methods in the diagnostic workup of deposits of melanocytes in lymph nodes that are histopathologically ambiguous .
Source: Dalton SR, Am J Surg Pathol 2010, 34:231-7
POPULATION ATTRIBUTABLE FRACTION (PAF)-1
In a meta-analysis of 49 studies, the PAF for people with > or =1 atypical nevi was 25% and for people with > or =25 common nevi was 42%.
Source: Olsen CM, Cancer Prev Res 2010, 3:233-45
TREMELIMUMAB PHASE II TRIAL
In this trial (n=251), tremelimumab showed an objective response rate of 6.6%, with all responses being durable > or =170 days.
Source: Kirkwood JM, Clin Cancer Res 2010, 16:1042-8
SWI/SNF COMPLEX
SWI/SNF chromatin remodeling complex is critical for the expression of MITF and could represent a novel therapeutic target.
Source: Vachtenheim J, Biochem Biophys Res Commun 2010, 392:454-9
IPILIMUMAB + DACARBAZINE
In a phase II trial (n=72), anti-CTLA4 antibody ipilimumab + DTIC yielded a 14.3% tumor response rate in patients with advanced melanoma (ipilimumab alone: 5.4%).
Source: Hersh EM, Invest New Drugs 2010, Epub ahead of print
NEOADJUVANT TEMOZOLOMIDE
In a phase II trial (n=19), neaodjuvant TMZ yielded 16% tumor response rate (similar to metastatic setting), independently of the MGMT promoter methylation status.
Source: Shah GD, Ann Oncol 2010, Epub ahead of print
TEMOZOLOMIDE + CISPLATIN
In a phase II trial (n=30), chemonaive patients treated with TMZ + CDDP showed high toxicity and no apparent benefit, tumor response being similar to single-agent therapy.
Source: Wierzbicka-Hainaut E, Melanoma Res 2010, 20:141-6
CYSTATIN E/M AND LEGUMAIN
In an in vitro model, human melanoma cells forced to express the cystein protease inhibitor cystatin E/M show decreased levels of legumain and reduced invasiveness.
Source: Briggs JJ, BMC Cancer 2010, 10:17
MELANOMA DORMANCY
In a German population of patients with TNM stage I-II melanoma (n=1881), 20 cases (1.1%) of late (> 10 years) recurrences were recorded.
Source: Hansel G, J Eur Acad Dermatol Venereol 2010, Epub ahead of print
MELANOMA STEM CELLS AND IMMUNITY
ABCB5+ melanoma initiating cells can increase the number of immunosuppressive T regulatory (Treg) cells.
Source: Schatton T, Cancer Res 2010, 70:697-708
MELAPRO AND RISK COUNSELING
MelaPRO is an algorithm that provides germline CDKN2A mutation probabilities and melanoma risk to individuals from melanoma-prone families; it seems to outperform the existing predictive model MELPREDICT.
Source: Wang W, Cancer Res 2010, 70:552-9
p21/WAF1/CIP1 AND MITF
Cell cycle inhibitor p21 stimulates MITF expression, which in turn enhances p21 expression: this might explain the tolerance of increased p21 levels found in some melanomas.
Source: Sestáková B, Pigment Cell Melanoma Res 2010, Epub ahead of print
PAX3, SOX10 AND MET
PAX3 and SOX10 activate expression of MET, which in turn promotes melanoma migration, invasion, resistance to apoptosis and cell growth.
Source: Mascarenhas JB, Pigment Cell Melanoma Res 2010, Epub ahead of print
NOTCH1 AND MELANOMA DEVELOPMENT
Active Notch1 confers a transformed phenotype to primary human melanocytes.
Source: Pinnix CC, Cancer Res 2009, 69:5312-20
NRG1/ERBB3 SIGNALING
NRG1/ERBB3 signaling plays an important role in melanocyte development and melanoma by inhibiting differentiation and promoting proliferation.
Source: Buac K, Pigment Cell Melanoma Res 2009, 22:773-84
MELANOMA SOMATIC MUTATIONS
A comprehensive catalogue of somatic mutations from a human melanoma genome has been published.
Source: Pleasance ED, Nature 2010, 463:191-6
FAMILIAL MELANOMA: ATTRIBUTABLE RISK
A meta-analysis shows that only a small percentage of melanoma cases (always less than 7%) are attributable to familial risk.
Source: Olsen CM, Cancer Epidemiol Biomarkers Prev 2010, 19:65-73
HIF1-ALPHA AND PROGNOSIS
Expression of hypoxia inducible factor 1 alpha is not associated with survival of patients (n=89) with cutaneous melanoma.
Source: Valencak J, Clin Exp Dermatol 2009, 34:e962-4
MARCO AND DENDRITIC CELLS
In a murine melanoma model, targeting MARCO (a novel member of the cell surface class A scavenger receptor family) leads to enhanced DC motility and anti-melanoma activity.
Source: Matsushita N, Cancer Immunol Immunother 2010, Epub ahead of print
LOW DOSE IFN: 18 VS 60 MONTHS
In a phase III RCT (n=850), low dose IFN alpha administered for 18 or 60 months yielded no different results in terms of survival.
Source: Hauschild A, J Clin Oncol 2010, 28:841-6
NEW MODEL FOR DE NOVO MELANOMA
A de novo melanoma model in RET mice that are heterozygous for Ednrb has been developed and suggests that reduced expression of Ednrb might facilitate melanoma development.
Source: Kumasaka MY, Cancer Res 2010, 70:24-9
MELANOMA PROPAGATING CELLS (MPC)
Tumor formation capability decreases for CD34+/p75-, CD34-/p75- and CD34-/p75+ melanoma cells, respectively. MPC are chemoresistant as compared to non-MPC.
Source: Held MA, Cancer Res 2010, 70:388-97
VITAMIN D RECEPTOR POLYMORPHISMS
Vitamin D receptor (VDR) polymorphisms are associated with both melanoma risk and progression.
Source: Halsall JA, Dermatoendocrinol 2009, 1:54-7
METHIONINE FREE DIET + CYSTEMUSTINE
In a phase II trial (n=20), this regimen led to a median survival of 4.6 months, with 2 long-duration stabilizations.
Source: Thivat E, Anticancer Res 2009, 29:5235-40
PLP2 AND MELANOMA METASTASIS
Forced expression of phospholipid protein 2 (PLP2) enhanced melanoma proliferation, adhesion and invasion in vitro and tumor metastasis in vivo.
Source: Sonoda Y, Oncol Rep 2010, 23:371-6
GENE SIGNATURE OF INVASIVENESS
Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes (MITF, EDNRB, DCT, TYR) and increased expression of genes involved in interaction with the extracellular environment (PLAUR, VCAN, HIF1-alpha).
Source: Jeffs AR, PLoS One 2009, 4:e8461
POLY-EPITOPE VACCINE
Poly-epitope vaccination yielded high rates of immunological responses but only one partial response and five disease stabilizations in 41 patients with advanced melanoma.
Source: Dangoor A, Cancer Immunol Immunother 2009 Epub ahead of print
ROLE OF INFLAMMASOME
An in vitro model suggests that IL-1-mediated autoinflammation contributes to development and progression of human melanoma.
Source: Okamoto M, J Biol Chem 2010, 285:6477-88
ABCA1 AND CURCUMIN RESISTANCE
Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells (ABCA1 should be considered as response marker).
Source: Bachmeier BE, Mol Cancer 2009, 8:129
HISTOLOGICAL REGRESSION AND SN STATUS
Primary melanoma histological regression is not an independent predictor of sentinel node (SN) status in a cohort of 397 patients.
Source: Socrier Y, Br J Dermatol 2009, Epub ahead of print
BORTEZOMIB + TEMOZOLOMIDE
In a phase I trial of bortezomib + temozolomide (n=19) the investigators defined the doses for phase II trials; one partial response and 4 disease stabilizations were observed.
Source: Su Y, Clin Cancer Res 2010, 16:348-57
E2F1 AND MELANOMA METASTASIS
In a xenograft model, inhibition of E2F1 expression (which targets EGFR expression) via small hairpin RNA (shRNA) shows anti-melanoma potential in vivo.
Source: Alla V, J Natl Cancer Inst 2010, 102:127-33
ELAFIN ANTI-MELANOMA ACTIVITY
In a xenograft model, protease inhibitor elafin shows anti-melanoma potential in vivo.
Source: Yu KS, Int J Cancer 2009, Epub ahead of print
SYNERGISM LBW242 + TLR3 LIGAND
In an in vitro model, SMAC mimetic LBW242 synergizes with TLR3 ligand Poly I:C to induce apoptosis of human melanoma cells.
Source: Weber A, Cell Death Differ 2009, Epub ahead of print
IPILIMUMAB PHASE II TRIAL
In a phase II dose-ranging trial (n=217) of this anti-CTLA4 antibody for metastatic melanoma, the best overall response rate was 11.1% for 10 mg/kg, 4.2% for 3 mg/kg, and 0% for 0.3 mg/kg (trend test P=0.0015).
Source: Wolchok JD, Lancet Oncol 2010, 11:155-64
ROLE OF PKC-BETA
PKC-beta expression is reduced in melanoma cell lines and its re-expression inhibits colony formation in soft agar, indicating a potential role of PKC-beta in tumor growth.
Source: Voris JP, Pigment Cell Melanoma Res 2009, Epub ahead of print
VEGF RECEPTOR EXPRESSION
In a large series of melanoma specimens (n=468), VEGFR2 expression was higher in metastatic melanoma, while VEGFR3 expression was higher in primary melanoma.
Source: Mehnert JM, Hum Pathol 2010, 41:375-84
2-DEOXY-D-GLUCOSE AND TRAIL
2-deoxy-D-glucose (2-DG) sensitizes human melanoma cells to TRAIL-induced apoptosis through XBP1-mediated upregulation of TRAILR2.
Source: Liu H, Mol Cancer 2009, 8:122
KIT MUTATION IN MUCOSAL MELANOMA
The Authors report on one case of anal mucosal melanoma positive for activating KIT mutation responding to imatinib and review the literature on similar cases (n=12).
Source: Satzger I, Dermatology 2010, 220:77-81
SORAFENIB + TEMOZOLOMIDE
In a 4-arm phase II RCT (n=167), the median progression free survival for patients on arm A, B, C, and D was 5.9, 4.2, 2.2, and 3.5 months, respectively.
Source: Amaravadi RK, Clin Cancer Res 2009, 15:7711-8
AKT ACTIVATION IN MELANOMA
In human melanoma metastases (n=96), phosphorylated AKT is more frequent in BRAF mutated than NRAS mutated specimens, is almost always associated with PTEN loss and is more frequent in brain metastases.
Source: Davies MA, Clin Cancer Res 2009, 15:7538-46
MEK + CDK4 INHIBITION
Combined inhibition of MEK and CDK4 leads to human melanoma cell apoptosis (in vitro) more potently than either inhibition alone.
Source: Li J, Cancer Invest 2009, Epub ahead of print
FALSE NEGATIVE SENTINEL NODES
In a large series of patients undergoing sentinel node (SN) biopsy (n=2451), the false negative rate was 10.8%, and the survival of patients with false negative SN was not worse than that of patients with true positive SN.
Source: Scoggins CR, Ann Surg Oncol 2010, 17:709-17
HEPARIN-DERIVED OLIGOSACCHARIDES
In a xenogtaft model, heparin-derived 4-18 unit oligosaccharides shows significant anti-melanoma activity.
Source: Kenessey I, Thromb Haemost 2009, 102:1265-73
M8 STILBENE PRECLINICAL ACTIVITY
In a xenogtaft model, 3,3',4,4',5,5'-Hexahydroxystilbene (M8) shows significant anti-melanoma activity.
Source: Paulitschke V, J Invest Dermatol 2009, Epub ahead of print
NANOTECHNOLOGY NEWS
In an in vivo preclinical model, single-walled carbon nanotube-conjugated doxorubicin shows increased therapeutic index against melanoma as compared to doxorubicin alone.
Source: Chaudhuri P, Nanotechnology 2010, 21:025102
DOCETAXEL + TEMOZOLOMIDE
In a retrospective study, this combination regimen has modest activity in patients with metastatic melanoma resistant to first line chemotherapy.
Source: Yoon C, Melanoma Res 2010, 20:43-7
CARBOXYLESTERASE AND CPT-11
Forced expression of carboxylesterase (which converts CPT-11 into SN-38) in neural stem cells significantly increases the anti-melanoma activity of CPT-11.
Source: Gutova M, Curr Stem Cell Res Ther 2009, Epub ahead of print
JWA AND MELANOMA
The microtubule-associated protein JWA suppresses melanoma metastasis in vivo, likely by inhibiting integrin alpha V beta 3 signaling.
Source: Bai J, Oncogene 2009, Epub ahead of print
PARTHENOLIDE PRECLINICAL ACTIVITY
Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro.
Source: Lesiak K, Melanoma Res 2010, 20:21-34
CAMPTOTHECIN ENHANCERS
Both bortezomib (NFkB inhibitor) and KINK-1 (IKKB inhibitor) can enhance the anti-melanoma activity of camptothecin in a preclinical model.
Source: Amschler K, J Invest Dermatol 2009, Epub ahead of print
DIMETHYLFUMARATE (DMF)
DMF increases the anti-melanoma effect of dacarbazine in a xenograft model.
Source: Valero T, J Invest Dermatol 2009, Epub ahead of print
NETRIN-1 AND MELANOMA
Netrin-1 is overexpressed in melanoma as compared to melanocytes and increases melanoma cell migratory potential in vitro.
Source: Kaufmann S, Cell Oncol 2009, 31:415-22
CELASTROL + TEMOZOLOMIDE
Celastrol enhances the anti-melanoma effect of temozolomide in a preclinical model, likely by inhibiting NFkB activity.
Source: Chen M, Mol Cancer Res 2009, 7:1946-53
MELANOMA FIBROBLASTS
Fibroblasts derived from metastatic melanomas can have strong immunosuppressive activity through NK cell modulation.
Source: Balsamo M, Proc Natl Acad Sci USA 2009, Epub ahead of print
HYPOXIA INDUCIBLE FACTOR 1 ALPHA (HIF1-alpha)
HIF1-alpha is overexpressed during melanoma progression and its inhibition has therapeutic potential in a preclinical model.
Source: Mills CN, Mol Cancer 2009, 8:104
THALIDOMIDE + TEMOZOLOMIDE
In a phase II trial (n=64), thalidomide plus temozolomide do not appear to provide a clinical benefit that exceeds dacarbazine alone.
Source: Clark JI, Cancer 2010, 116:424-31
MAINTENANCE BIOTHERAPY
In a phase II trial (n=133), maintenance biotherapy after induction concurrent biochemotherapy appears to improve the survival of patients with metastatic melanoma.
Source: O'Day SJ, J Clin Oncol 2009, 27:6207-12
IMMUNE PROFILE AND MITOTIC INDEX
Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.
Source: Bogunovic D, Proc Natl Acad Sci USA 2009, 106:20429-34
c-JUN, PKDK1 AND AKT
c-Jun is a transcriptional regulator of PDK1 expression, which highlights key mechanisms underlying c-Jun oncogenic activity and provides new insight into the nature of upregulated Akt and PKC in melanoma.
Source: Lopez-Bergami P, J Biol Chem 2010, 285:903-13
ROLE OF DE-N-ACETYL-GM3
De-N-acetyl GM3 (a derivative of ganglioside GM3) promotes melanoma cell migration and invasion through urokinase plasminogen activator receptor signaling-dependent MMP-2 activation.
Source: Liu JW, Cancer Res 2009, 69:8662-9
TM9SF4 AND MELANOMA CANNIBALISM
Tumor cannibalism is a characteristic of malignancy and metastatic behavior: silencing of TM9SF4 inhibits cannibal activity of human melanoma cells, representing a potential new target for anticancer strategies.
Source: Lozupone F, EMBO Rep 2009, 10:1348-54
NFkB INHIBITION IN UVEAL MELANOMA
Pharmacological inhibition of NFkB reduces proliferation and induces apoptosis of human uveal metastatic melanoma cells in vitro.
Source: Dror R, Invest Ophthalmol Vis Sci 2009, Epub ahead of print
PARP INHIBITION BY PJ-34
Inhibition of PARP activity by PJ-34 leads to growth impairment and cell death in M14 melanoma cell line.
Source: Chevanne M, J Cell Physiol 2010, 222:401-10
3-MARKER PROGNOSTIC SIGNATURE
The expression of 3 biomarkers (NCOA3, SPP1, RGS1) independently predicts survival of patients with melanoma.
Source: Kashani-Sabet M, Clin Cancer Res 2009, 15:6987-92
5-MARKER PROGNOSTIC SIGNATURE
The expression of 5 biomarkers (ATF2, p21/WAF1, p16/INK4A, beta-catenin) independently predicts survival of patients with melanoma.
Source: Gould Rothberg BE, J Clin Oncol 2009, 27:5772-80
GMCSF AND ONCOLYTIC VIRUS
In a phase II clinical trial of a GMCSF-encoding oncolytic herpesvirus, promising tumor response (26%) and survival (52% at 2 years) rates were observed.
Source: Senzer NN, J Clin Oncol 2009, 27:5763-71
BRAF V600E AND MAP2
Oncogenic BRAF V600E induces expression of neuronal differentiation marker MAP2 in melanoma cells by promoter demethylation and downregulation of transcription repressor HES1.
Source: Maddodi N, J Biol Chem 2010, 285:242-54
ROLE OF Treg CELL DEPLETION
In a RET transgenic mouse model of melanoma, depletion of CD25+Foxp3+ regulatory T cells with anti-CD25 mAb does not prevent tumor development.
Source: Kimpfler S, J Immunol 2009, 183:6330-7
ELESCLOMOL PLUS PACLITAXEL
In a phase II randomized trial (n=81), elesclomol (oxidative stress inducer) improved the therapeutic activity of paclitaxel in terms of progression free survival.
Source: O'Day S, J Clin Oncol 2009, 27:5452-8
VITAMIN D3 SERUM LEVELS
In a cohort of 872 patients, serum levels of vitamin D3 correlated with primary melanoma thickness and patients' survival.
Source: Newton-Bishop JA, J Clin Oncol 2009, 27:5439-44
LOCOREGIONAL RELAPSE AND NODE STATUS
The rate of locoregional (including in transit) metastases in patients with tumor-positive sentinel node (n=141) and patients with palpable nodal involvement (n=178) is similar.
Source: Veenstra HJ, Ann Surg Oncol 2009, Epub ahead of print
CONJUNCTIVAL MELANOMA INCIDENCE
In a Swedish study, the incidence of conjunctival melanoma significantly increased during the period 1960 to 2005.
Source: Triay E, Br J Ophthalmol 2009, 93:1524-8
STAT3 INHIBITION
In a xenograft model, STAT3 inhibition by antisense technology suppresses melanoma growth in vivo.
Source: Yang L, Cancer Biol Ther 2009, 8:2065-72
HYPERTENSION DRUGS AND MELANOMA RISK
In a case-control study (cases=1272), the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was not significantly associated with melanoma risk.
Source: Koomen ER, Cancer Epidemiol 2009, 33:391-5
SKIN SELF-EXAMINATION (SSE)
In a retrospective study (n=321), SSE was associated with decreased tumor thickness (adjusted ratio, 0.75; 95% CI: 0.66-0.85 for ever versus never use).
Source: Pollitt RA, Cancer Epidemiol Biomarkers Prev 2009, 18:3018-23
SENTINEL NODE TUMOR BURDEN
The EORTC Melanoma Group has released the recommendations on the measurement of sentinel node tumor burden for prognostic purpose.
Source: van Akkooi AC, Eur J Cancer 2009, 45:2736-42
SURGERY FOR LIVER METASTASIS
A non randomized study (n=255) showed longer survival for patients undergoing radical versus non radical hepatic resection for melanoma metastasis.
Source: Mariani P, Eur J Surg Oncol 2009, 35:1192-7
BIOMARKERS OF RESPONSE TO IL-2
Serum VEGF and fibronectin can predict clinical response to high dose interleukin-2 (n=59).
Source: Sabatino M, J Clin Oncol 2009, 27:2645-52
RANTES + GP100 VACCINE
In a gene therapy model, vaccination with chemokine RANTES and melanoma antigen gp100 is more effective than with gp100 alone.
Source: Aravindaram K, Gene Ther 2009, 16:1329-39
MODIFIED HEPARINS
Modified heparins inhibit integrin alpha(IIb)beta(3) mediated adhesion of melanoma cells to platelets in vitro and in vivo.
Source: Zhang C, Int J Cancer 2009, 125:2058-65
CDKN2A MUTATION RATE IN FAMILIAL MELANOMA
An Italian study showed that CDKN2A is mutated in 68/204 (33%) families with at least two members affected with melanoma.
Source: Bruno W, J Am Acad Dermatol 2009, 61:775-82
D2-40 DOES NOT PREDICT SENTINEL NODE STATUS
D2-40/S-100 dual immunohistochemistry increases the sensitivity of detection of lymphatic invasion in melanoma but does not predict sentinel lymph node involvement (n=27).
Source: Petitt M, J Am Acad Dermatol 2009, 61:819-28
D2-40 PROGNOSTIC AND PREDICTIVE VALUE
Expression of D2-40 (lymphatic invasion biomarker) in primary melanoma predicts sentinel lymph node status and correlates with survival (n=60).
Source: Petersson F, J Cutan Pathol 2009, 36:1157-63
ROLE OF MMP-13
Stromal expression of matrix metalloproteinase-13 is required for melanoma invasion and metastasis, as demonstrated in a gene knockout model.
Source: Zigrino P, J Invest Dermatol 2009, 129:2686-93
KIT EXPRESSION AND MUTATION
In a series of 173 melanomas, eighty-two percent (12 of 14) of cases positive for KIT mutation showed KIT expression in more than 50% of the cells.
Source: Torres-Cabala CA, Mod Pathol 2009, 22:1446-56
IGFBP7 AND MUTATED BRAF
In melanomas carrying oncogenic mutated BRAF, IGFBP7 is epigenetically silenced; systemically administered recombinant IGFBP7 suppresses the growth of BRAF-positive primary tumors in xenografted mice.
Source: Wajapeyee N, Mol Cancer Ther 2009, 8:3009-14
ADJUVANT IFN FOR UVEAL MELANOMA
In a non randomized trial, low dose adjuvant interferon alpha provides no survival benefit to patients with high risk uveal melanoma.
Source: Lane AM, Ophthalmology 2009, 116:2206-12
PHORBOL ESTER PARADOXICAL ACTIVITY
The tumor-promoting phorbol ester TPA inhibits melanoma growth by inactivation of STAT3 through a PKC activated tyrosine phosphatase.
Source: Oka M, J Biol Chem 2009, 284:30416-23
ADAM10 and L1-CAM
ADAM10 is overexpressed in metastatic as compared to primary melanoma; it is associated with melanoma invasiveness and releases L1-CAM, which is responsible for chemoresistance.
Source: Lee SB, J Invest Dermatol 2009, Epub ahead of print
EAPB0203 PRECLINICAL ACTIVITY
In a xenografted mouse in vivo model, EAPB0203 (a novel imidazo[1,2-a]quinoxaline derivative) is more effective than fotemustine against melanoma.
Source: Khier S, Eur J Pharm Sci 2009, Epub ahead of print
RAPAMYCIN PRECLINICAL ACTIVITY
In a mouse syngeneic model, mTOR inhibitor rapamycin inhibits lung metastasis through downregulation of alpha V integrin expression and upregulation of apoptosis signaling.
Source: Yang Z, Cancer Sci 2009, Epub ahead of print
NESTIN, SOX9 AND SOX10
SOX9 and SOX10 are highly expressed in melanoma and seem to have a regulatory role in Nestin expression; nestin and SOX9 may be negative prognostic markers.
Source: Bakos RM, Exp Dermatol 2009, Epub ahead of print
INDUCIBLE NITRIC OXIDE SYNTHASE (iNOS)
In patients with uveal melanoma (n=90), iNOS expression is not an independent prognostic factor at multivariable survival analysis.
Source: Johansson CC, Int J Cancer 2009, Epub ahead of print
CAFFEIC ACID PHENETYL ESTER (CAPE)
In an mouse melanoma model, CAPE shows anti-melanoma activity in vivo.
Source: Kudugunti SK, Invest New Drugs 2009, Epub ahead of print
BRAF, NFAT AND COX2
Oncogenic BRAF V600E activates NFAT2 and NFAT4 via MEK/ERK signaling, which leads to COX2 upregulation in metastatic melanoma.
Source: Flockhart RJ, Br J Cancer 2009, 101:1448-55
US-GUIDED FNAC AND SNB
Ultrasound-guided fine needle aspiration cytology of sentinel nodes is highly accurate and can lead to significant reduction of SN biopsy procedures.
Source: Voit CA, J Clin Oncol 2009, 27:4994-5000
PARKINSON DISEASE AND MELANOMA
A cohort study (n=157,036) showed a significant association between a positive family history of melanoma and risk of PD (multivariate relative risk = 1.85; 95%CI = 1.2-2.8).
Source: Gao X, Neurology 2009, 73:1286-91
ADH-1 FOR ISOLATED LIMB INFUSION
In a phase I trial (n=16), isolated limb infusion with melphalan combined with ADH-1 (a N-cadherin inhibitor) yielded a high complete response rate (50%).
Source: Beasley GM, Cancer 2009, 115:4766-74
PHOTOACUSTIC FLOW CYTOMETRY
Two color photoacustic flow cytometry with diode laser can reliably detect up to 1 melanoma cell per ml, which can be relevant for searching circulating melanoma cells.
Source: Galanzha EI, Cancer Res 2009, 69:7926-34
SNF5 TUMOR SUPPRESSOR GENE
SNF5, the core subunit of SWI/SNF complex, is downregulated in melanoma, which correlates with poor patients' prognosis; in vitro, SNF5 knockdown causes chemoresistance.
Source: Lin H, Clin Cancer Res 2009, 15:6404-11
MC1R VARIANTS AND MELANOMA RISK
In this case-control study (n=1,185), red hair color (RHC) and non-RHC melanocortin receptor 1 (MC1R) variants were the major contributors for melanoma risk in the German and Spanish population, respectively.
Source: Scherer D, Int J Cancer 2009, 125:1868-75
YM155 PHASE II TRIAL
In this trial (n=34), YM155 (a survivin inhibitor) failed to demonstrate significant anti-melanoma activity.
Source: Lewis KD, Invest New Drugs 2009, Epub ahead of print
MELANOMA THICKNESS TRENDS
An analysis of the SEER database revealed that over the past 20 years the proportion of melanoma in situ has increased, while thick melanoma proportion has remained substantially unchanged.
Source: Criscione VD, J Invest Dermatol 2009, Epub ahead of print
MIR-15B AND MELANOMA
MicroRNA-15b represents is an independent prognostic factor and increases melanoma cell proliferation and survival.
Source: Satzger I, Int J Cancer 2009, Epub ahead of print
LACUNARITY ANALYSIS
Lacunarity analysis (a simple statistical measure used for the analysis of fractal and multi-scaled images) of digitized dermoscopic images could help clinicians to diagnose cutaneous melanoma.
Source: Gilmore S, PLoS One 2009, 4:e7449
CD40L PLUS TLR AGONISTS
In an in vivo mouse melanoma model, nanoparticle-delivered multimeric soluble CD40L DNA show synergistic therapeutic effect combined with toll-like receptor (TLR) agonists.
Source: Stone GW, PLoS One 2009, 4:e7334
EXCISION MARGINS META-ANALYSIS
According to a Cochrane meta-analysis of randomized controlled trials, primary melanoma excision margins (wide vs narrow) do not affect patients' overall survival.
Source: Sladden MJ, Cochrane Database Syst Rev 2009, CD004835
WARNING ON PI-103
In an in vivo mouse melanoma model, PI-103 - a dual PI3K (p110alpha)/mTOR inhibitor - has no synergistic effect with sorafenib (BRAF/CRAF inhibitor), may cause immunosuppression, inhibit apoptosis and ultimately favor tumor growth.
Source: López-Fauqued M, Int J Cancer 2009, Epub ahead of print
KIT AND HIF-1 alpha
c-Kit mutant melanocytes show activation of PI3K pathway that is not sufficient for transformation; combination with HIF-1 forced expression leads to Ras/Raf/Mek/Erk pathway activation and melanocyte transformation.
Source: Monsel G, Oncogene 2009, Epub ahead of print
TYRO3 AND MITF
The receptor protein tyrosine kinase TYRO3 is an upstream regulator of MITF expression; its knockdown shows antimelanoma activity in a xenograft model and acts as a chemosensitizer.
Source: Zhu S, Proc Natl Acad Sci USA 2009, 106:17025-30
ROR2 AND WNT5A
The orphan tyrosine kinase receptor ROR2 mediates Wnt5A signaling in metastatic melanoma and its silencing shows antimelanoma activity in an in vivo mouse model.
Source: O'Connell MP, Oncogene 2009, Epub ahead of print
PAEP FUNCTIONAL CHARACTERIZATION
Silencing of PAEP (progestagen-associated endometrial protein) shows anti-melanoma activity in a xenograft model.
Source: Ren S, J Cell Mol Med 2009, Epub ahead of print
EPAC AND MIGRATION
Silencing of EPAC (an effector molecule of cAMP) inhibits melanoma cell migration.
Source: Baljinnyam E, Am J Physiol Cell Physiol 2009, 297:C802-13
MT1 MELATONIN RECEPTOR
MT1 melatonin receptor is expressed in primary melanoma and correlates with tumor thickness.
Source: Danielczyk K, Anticancer Res 2009, 29:3887-95
MITF AND BRAF V600E
In an in vitro model of human melanoma, silencing of MITF synergically increases the cytotoxic effect of BRAF V600E silencing.
Source: Kido K, Cancer Sci 2009, 100:1863-9
TREMELIMUMAB + VACCINE
In a phase I-II trial (n=16), MART-1 peptide-pulsed dendritic cells and tremelimumab resulted in objective and durable tumor responses at the higher range of the expected response rate with either agent alone.
Source: Ribas A, Clin Cancer Res 2009, 15:6267-76
ONCOLYTIC REOVIRUS
In a murine in vivo melanoma model, oncolytic Reovirus increases the antitumor activity of cisplatin.
Source: Pandha HS, Clin Cancer Res 2009, 15:6158-66
ADJUVANT RADIOTHERAPY
In a retrospective study (n=77), adjuvant radiotherapy after lymph node dissection yields a high locoregional control rate, although distant metastases remain the major cause of mortality.
Source: Conill C, Clin Transl Oncol 2009, 11:688-93
SNB RECOMMENDATIONS
The European Association of Nuclear Medicine (EANM) and the EORTC have jointly released the recommendations for sentinel node biopsy in melanoma.
Source: Chakera AH, Eur J Nucl Med Mol Imaging 2009, 36:1713-42
HSV2 MUTANT DeltaPK
The growth defective herpes simplex virus type 2 mutant deltaPK shows significant antitumor activity in a xenograft model of human melanoma.
Source: Colunga AG, Gene Ther 2009, Epub ahead of print
MELANOMA INHIBITORY ACTIVITY (MIA)
MIA protein is highly expressed and secreted by malignant melanoma cells and plays an important role in melanoma development, progression and tumor cell invasion.
Source: Schmidt J, Int J Cancer 2009, 125:1587-94
CAVEOLIN-1
In an in vitro model, caveolin-1 promotes human melanoma progression as indicated by enhanced proliferation, migration, invasion and foci formation in semisolid medium.
Source: Felicetti F, Int J Cancer 2009, 125:1514-22
ARTEMISININ
Artemisinin (an antimalarial drug) reduces human melanoma cell migration by downregulating alpha V beta 3 integrin and metalloproteinase-2.
Source: Buommino E, Invest New Drugs 2009, 27:412-8
FAMILIAL MELANOMA IDENTIFICATION
In this review article, the Authors found that CDKN2A germline mutations (responsible for about 2% of melanomas) are more frequent in individuals with 3 or more primary invasive melanomas.
Source: Leachman SA, J Am Acad Dermatol 2009, 61:677.e1-14
MOESIN AND INVASION
In a 3D model, moesin orchestrates cortical polarity of melanoma cells, which may drive tumor vertical migration instead of superficial spreading.
Source: Estecha A, J Cell Sci 2009, 122(Pt 19):3492-501
MELANOMA REPROGRAMMING
Mouse melanoma cells can be reprogrammed into induced pluripotent stem cells, which suggests that cancer cells remain susceptible to transcription factor-mediated reprogramming.
Source: Utikal J, J Cell Sci 2009, 122(Pt 19):3502-10
PET VERSUS CT FOR STAGING
In a prospective comparison (n=251), PET and CT were equivqlent in upstaging; treatment changed in 19% of patients (79% using both scans, 17% only by PET, 4% only by CT).
Source: Bastiaannet E, J Clin Oncol 2009, 27:4774-80
WT1 AND MELANOMA DIAGNOSIS
Wilms' tumor 1 (WT1) protein expression is not helpful for the diagnosis of skin melanoma in a series of 45 cases.
Source: Rosner K, J Cutan Pathol 2009, 36:1077-82
SILIBININ AND MITOMYCIN-C
In an in vitro model, silibinin (a flavonoid from plant-derived silymarin) protects melanoma cells from mitomycin-C cytotoxicity.
Source: Jiang YY, J Pharmacol Sci 2009, 111:137-46
MELANOMA SPONTANEOUS REGRESSION
A review of the literature on the phenomenon of metastatic melanoma spontaneous regression reveals a total of 76 reported cases since 1866.
Source: Kalialis LV, Melanoma Res 2009, 19:275-82
ESTROGENS AND TUMOR THICKNESS
A retrospective Dutch study (n=687), use of estrogens is not associated with primary melanoma thickness.
Source: Koomen ER, Melanoma Res 2009, 19:327-32
GALLIUM COMPLEX KP46
In an in vitro model, gallium complex KP46 shows strong anti-melanoma activity.
Source: Valiahdi SM, Melanoma Res 2009, 19:283-93
GALECTIN-3 AND PROGNOSIS
Serum levels of galectin-3 may have an independent prognostic value in stage III-IV melanoma patients.
Source: Vereecken P, Melanoma Res 2009, 19:316-20
LAMININ-421 AND MIGRATION
In an in vitro model, antibody blockage of lymphatic endothelial cell laminin-421 inhibits migratory ability of melanoma cells.
Source: Saito N, Pigment Cell Melanoma Res 2009, 22:601-10
FOLATE RECETOR ALPHA AND METHOTREXATE
In an in vitro model, folate receptor mediated sequestration of methotrexate (MTX) in melanosomes may be targeted to overcome melanoma resistance to MTX.
Source: Sánchez del Campo L, Pigment Cell Melanoma Res 2009, 22:588-600
CREB AND CYR61
In an in vivo model, stable silencing of cAMP-response element-binding protein (CREB) expression in human metastatic melanoma cell lines suppresses tumor growth and experimental metastasis by downregulating cysteine-rich protein 61 (CCN1/CYR61) expression.
Source: Dobroff AS, J Biol Chem 2009, 284:26194-206
INDUCING MELANOMA DIFFERENTIATION
Induction of terminal differentiation in melanoma cells by downregulation of beta-amyloid precursor protein (APP) impairs cell proliferation and improves chemosensitivity.
Source: Bothelho MG, J Invest Dermatol 2009, Epub ahead of print
MART1 + P40 VACCINE
In a pilot study (n=14), vaccination with Melan-A/Mart-1 peptide and Klebsiella protein P40 as an adjuvant induced ex vivo detectable tumor antigen specific T cell responses in 6 patients.
Source: Lienard D, J Immunother 2009, Epub ahead of print
NEW MELANOMA ANTIGEN MELOE-2
An additional open reading frame (ORF) on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context.
Source: Godet Y, Cancer Immunol Immunother 2009, Epub ahead of print
LOSARTAN PRECLINICAL ACTIVITY
In an in vivo murine melanoma model, inhibition of angiotensin II receptor 1 (AT1) by losartan limits tumor angiogenesis and growth.
Source: Otake AH, Cancer Chemother Pharmacol 2009, Epub ahead of print
EARLY VS LATE ONSET MELANOMA
Using the SEER database, investigators found epidemiological differences between early and late onset melanomas.
Source: Anderson WF, Cancer 2009, 115:4176-85
CAR-T CELLS PRECLINICAL ACTIVITY
In a xenograft model, immunotherapy of metastatic human melanoma using chimeric antigen receptors (CAR) engineered ganglioside GD2-specific T cells increases the survival of tumor-bearing animals.
Source: Yvon E, Clin Cancer Res 2009, 15:5852-60
GPIbalpha AND METASTASIS
In a mouse in vivo model, platelet glycoprotein Ib alpha (GPIbalpha) inhibition promotes melanoma metastasis.
Source: Erpenbeck L, J Invest Dermatol 2009, Epub ahead of print
PET META-ANALYSIS
A meta-analysis of 24 sudies shows that (18)F-FDG positron emission tomography is not useful to detect regional metastases, but could be useful to detect distant metastases.
Source: Jiménez-Requena F, Eur J Nucl Med Mol Imaging 2009, Epub ahead of print
ERBB4 MUTATIONS
ERBB4/HER4 mutations were found in 19% of individuals with melanoma (n=79); melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA-mediated knockdown of ERBB4 or treatment with ERBB inhibitor lapatinib.
Source: Prickett TD, Nat Genet 2009, 41:1127-32
SYNTAXIN-7
Using an antibody-based proteomics approach, investigators found that Syntaxin-7 (STX7) is selectively expressed in melanocytes and melanoma.
Source: Strömberg S, J Proteome Res 2009, 8:1639-46
OBESITY AND PROGRESSION
In a mouse melanoma model, obesity enhances melanoma growth in vivo, possibily by upregulation of VEGF pathways.
Source: Brandon EL, Cancer Biol Ther 2009, Epub ahead of print
MENADIONE AND SIAH2
Menadione is a specific inhibitor of SIAH2 ubiquitin ligase; in vivo, it inhibits the growth of xenograft melanoma.
Source: Shah M, Pigment Cell Melanoma Res 2009, 22:799-808
POSITIVE NON-SENTINEL LYMPH NODE (NSLN)
Among node-positive melanoma patients (n=429), presence of a positive NSLN is a highly significant poor prognostic sign, which warrants completion lymph node dissection after a positive SLN.
Source: Ghaferi AA, Ann Surg Oncol 2009, 16:2978-84
DNA REPAIR GENE POLYMORPHISMS
A meta-analysis (cases=4,195) reveals that XPD/ERCC2 single nucleotide polymorphism rs13181 is associated with risk of melanoma development.
Source: Mocellin S, Carcinogenesis 2009, 30:1735-43
MELANOSOMES AND CHEMORESISTANCE
In an vitro model, melanosome dynamics (e.g. biogenesis, density, status and structural integrity) modulates the drug resistance of melanoma cells.
Source: Chen KG, J Natl Cancer Inst 2009, 101:1259-71
PAR1, PAFR AND METASTASIS
Protease-activated receptor-1 (PAR1) and platelet-activating factor receptor (PAFR) induce melanoma cell adhesion molecule (MCAM/MUC18) expression and favor melanoma metastasis.
Source: Melnikova VO, J Biol Chem 2009, 284:28845-55
FKBP51 AND RADIOSENSITIZATION
Inhibition of FK506-binding protein 51 (FKBP51, an immunophilin with isomerase activity) greatly enhances radiotherapy efficacy in a xenograft melanoma model.
Source: Romano S, Cell Death Differ 2009, Epub ahead of print
NEW TNM STAGING SYSTEM
The latest version of the AJCC TNM staging system for cutaneous melanoma has been released (based on 30,946 cases). Main changes: 1) mitotic rate (added); 2) Clark level (removed). Main limit: no molecular biomarker has been implemented. The details are available in the TNM Staging section of the MMMP website.
Source: Balch CM, J Clin Oncol 2009, Epub ahead of print
SYNDECANS AND WNT5A
Heparan sulfate proteoglycans syndecan 1 and 4 are key components of the Wnt5A autocrine signaling, the activation of which leads to increased metastasis of melanoma.
Source: O'Connell MP, J Biol Chem 2009, 284:28704-12
US SCAN FOR PRIMARY THICKNESS
In a small study (n=53), preoperative 10-MHz sonography could discriminate thick (> 1 mm) from thin melanomas with promising accuracy.
Source: Vilana R, AJR Am J Roentgenol 2009, 193:639-43
CHEST X-RAY QUESTIONED
In 248 patients undergoing SNB, preoperative chest X-ray did not identify pulmonary metastasis and did not change planned treatment strategies.
Source: Vermeeren L, J Surg Res 2009, Epub ahead of print
NOVEL PET RADIOTRACER
A new melanoma positron emission tomography (PET) imaging radiotracer has been developed with high tumor-to-body contrast ratio and rapid renal clearance.
Source: Greguric I, J Med Chem 2009, 52:5299-302
4-HYDROXYCOUMARIN PRECLINICAL ACTIVITY
Anticoagulat 4-hydroxycoumarin (4-HC) resulted effective against melanoma in an in vivo mouse model.
Source: Salinas-Jazmín N, Cancer Chemother Pharmacol 2009, Epub ahead of print
LUMCORIN AND MIGRATION
In an in vitro study, lumcorin (a peptide derived from human lumican) inhibits melanoma migration.
Source: Zeltz C, FEBS Lett 2009, 583:3027-32
MELANOMA DETECTION ABILITY
An Australial study showed that the ability of skin cancer clinics to detect melanoma is similar to that of mainstream general practice and worse than specialist practice.
Source: Hansen C, J Am Acad Dermatol 2009, 61:599-604
WHOLE BRAIN RADIOTHERAPY (WBRT)
A small retrospective study (n=51) suggests that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy.
Source: Rades D, Int J Radiat Oncol Biol Phys 2009, Epub ahead of print
MELANOMA EPIDEMIC
In a study conduced in East Anglia, melanoma incidence increased from 9.39 to 13.91 cases/100,000/year, while overall mortality only increased from 2.16 to 2.54 cases/100,000/year.
Source: Levell NJ, Br J Dermatol 2009, 161:630-4
DTIC +/- PF3512676
In a phase II-III RCT, the addition of CpG oligodeoxynucleotide PF-3512676 does not add significant tumor response advantage to dacarbazine alone.
Source: Weber J, Cancer 2009, 115:3944-54
HLA MOLECULES EXPRESSION
Investigators have assessed the expression of HLA class I and II molecules in a large panel of human melanoma cell lines.
Source: Mendez R, Cancer Immunol Immunother 2009, 58:1507-15
ADHESION MOLECULES EXPRESSION
Investigators have assessed the expression of adhesion molecules and ligands for receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines.
Source: Casado JG, Cancer Immunol Immunother 2009, 58:1517-26
IPILIMUMAB PLUS BUDESONIDE
A phase II RCT showed that budesonide (an oral non-absorbed corticostroid) does not prevent dyarrhea in patients taking anti-CTLA4 ipilimumab.
Source: Weber J, Clin Cancer Res 2009, 15:5591-8
CXCL8 AND ITS RECEPTORS
In a human melanoma preclinical model, CXCL8 induces cell proliferation and angiogenesis; inhibition of its receptors (CXCR1 and CXCR2) shows promising therapeutic potential.
Source: Gabellini C, Eur J Cancer 2009, 45:2618-27
NBDHEX PRECLINICAL ACTIVITY
6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) induces JNK activation and apoptosis, and appears effective against human melanoma in both in vitro and in vivo preclinical models.
Source: Pellizzari Tregno F, Eur J Cancer 2009, 45:2606-17
TIL AND SENTINEL NODE STATUS
An Italian study (n=404) showed a significant correlation between the presence of tumor infiltrating lymphocytes (TIL) and sentinel node status.
Source: Mandalŕ M, Eur J Cancer 2009, 45:2537-45