Melanoma Program

The DF/HCC Melanoma Program continues to drive discovery in the melanoma field. Its broad mission is to integrate discoveries in the laboratory with research initiatives in the clinic. The program emphasizes inter-institutional and transdisciplinary research interactions and collaborations, with publications and ongoing clinical trials as evidence of success.

Program members are national and international leaders in the study of preclinical and clinical aspects of melanoma and non-melanoma skin cancers, thus supporting the program’s goal of contributing to the local and national scientific agenda. Members are also thought leaders in the use of targeted signaling pathway antagonists and immunotherapeutic strategies for treatment of melanoma. The program’s deep laboratory backdrop provides a strong flow of clinical specimens for cutting-edge molecular characterization, often linked to clinical annotation. Currently, there are more than 40 members in the Melanoma Program.

Recent Publications

  • Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015; 373:23-34. PubMed
  • Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015; 372:2006-17. PubMed
  • DeRan M, Yang J, Shen CH, Peters EC, Fitamant J, Chan P, Hsieh M, Zhu S, Asara JM, Zheng B, Bardeesy N, Liu J, Wu X. Energy stress regulates hippo-YAP signaling involving AMPK-mediated regulation of angiomotin-like 1 protein. Cell Rep 2014; 9:495-503. PubMed
  • Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, Leming P, Puzanov I, Shin D, Kirkwood JM. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA 2014; 312:1744-53. PubMed
  • Konieczkowski DJ, Johannessen CM, Abudayyeh O, Kim JW, Cooper ZA, Piris A, Frederick DT, Barzily-Rokni M, Straussman R, Haq R, Fisher DE, Mesirov JP, Hahn WC, Flaherty KT, Wargo JA, Tamayo P, Garraway LA. A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. 2014. PubMed
  • Cooper ZA, Juneja VR, Sage PT, Frederick DT, Piris A, Mitra D, Lo JA, Hodi FS, Freeman GJ, Bosenberg MW, McMahon M, Flaherty KT, Fisher DE, Sharpe AH, Wargo JA. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res 2014. PubMed
  • Larson AR, Dresser KA, Zhan Q, Lezcano C, Woda BA, Yosufi B, Thompson JF, Scolyer RA, Mihm MC, Shi YG, Murphy GF, Lian CG. Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors. Mod Pathol 2014. PubMed
  • Ackerman A, Klein O, McDermott DF, Wang W, Ibrahim N, Lawrence DP, Gunturi A, Flaherty KT, Hodi FS, Kefford R, Menzies AM, Atkins MB, Long GV, Sullivan RJ. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer 2014. PubMed
  • Luo X, Mitra D, Sullivan RJ, Wittner BS, Kimura AM, Pan S, Hoang MP, Brannigan BW, Lawrence DP, Flaherty KT, Sequist LV, McMahon M, Bosenberg MW, Stott SL, Ting DT, Ramaswamy S, Toner M, Fisher DE, Maheswaran S, Haber DA. Isolation and molecular characterization of circulating melanoma cells. Cell Rep 2014. PubMed
  • Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32:1020-30. PubMed
  • Deperalta DK, Hoang MP, Tanabe KK. Approaches to regional nodes in patients with melanoma. J Clin Oncol 2014; 32:881-5. PubMed
  • Luke JJ, Lezcano C, Hodi FS, Murphy GF. Antitumor Granuloma Formation by CD4+ T Cells in a Patient With Rapidly Progressive Melanoma Experiencing Spiking Fevers, Neuropathy, and Other Immune-Related Toxicity After Treatment With Ipilimumab. J Clin Oncol 2014. PubMed
  • Schlapbach C, Gehad A, Yang C, Watanabe R, Guenova E, Teague JE, Campbell L, Yawalkar N, Kupper TS, Clark RA. Human TH9 cells are skin-tropic and have autocrine and paracrine proinflammatory capacity. Sci Transl Med 2014; 6:219ra8. PubMed
  • Wagle N, Van Allen EM, Treacy DJ, Frederick DT, Cooper ZA, Taylor-Weiner A, Rosenberg M, Goetz EM, Sullivan RJ, Farlow DN, Friedrich DC, Anderka K, Perrin D, Johannessen CM, McKenna A, Cibulskis K, Kryukov G, Hodis E, Lawrence DP, Fisher S, Getz G, Gabriel SB, Carter SL, Flaherty KT, Wargo JA, Garraway LA. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. 2014; 4:61-8. PubMed
  • Johannessen CM, Johnson LA, Piccioni F, Townes A, Frederick DT, Donahue MK, Narayan R, Flaherty KT, Wargo JA, Root DE, Garraway LA. A melanocyte lineage program confers resistance to MAP kinase pathway inhibition. Nature 2013; 504:138-42. PubMed
  • Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC, Van Otterloo E, Kim RS, Bergsteinsdottir K, Ogmundsdottir MH, Magnusdottir E, Mishra PJ, Davis SR, Guo T, Zaidi MR, Helgason AS, Sigurdsson MI, Meltzer PS, Merlino G, Petit V, Larue L, Loftus SK, Adams DR, Sobhiafshar U, Emre NC, Pavan WJ, Cornell R, Smith AG, McCallion AS, Fisher DE, Stefansson K, Sturm RA, Steingrimsson E. A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Cell 2013; 155:1022-33. PubMed
  • Cooper ZA, Frederick DT, Juneja VR, Sullivan RJ, Lawrence DP, Piris A, Sharpe AH, Fisher DE, Flaherty KT, Wargo JA. BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes. Oncoimmunology 2013; 2:e26615. PubMed
  • Shen CH, Yuan P, Perez-Lorenzo R, Zhang Y, Lee SX, Ou Y, Asara JM, Cantley LC, Zheng B. Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell proliferation. Mol Cell 2013. PubMed
  • Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, Bosenberg MW, McMahon M, Cantley LC, Zheng B. Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc Natl Acad Sci U S A 2013. PubMed
  • Sullivan RJ, Lorusso PM, Flaherty KT. The intersection of immune-directed and molecularly targeted therapy in advanced melanoma: where we have been, are, and will be. Clin Cancer Res 2013; 19:5283-91. PubMed
  • Fisher DE, Geller AC. Disproportionate burden of melanoma mortality in young U.S. men: the possible role of biology and behavior. JAMA Dermatol 2013; 149:903-4. PubMed
  • Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, Van den Abbeele AD, Demetri GD, Fisher DE. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol 2013; 31:3182-90. PubMed
  • Basu A, Bodycombe NE, Cheah JH, Price EV, Liu K, Schaefer GI, Ebright RY, Stewart ML, Ito D, Wang S, Bracha AL, Liefeld T, Wawer M, Gilbert JC, Wilson AJ, Stransky N, Kryukov GV, Dancik V, Barretina J, Garraway LA, Hon CS, Munoz B, Bittker JA, Stockwell BR, Khabele D, Stern AM, Clemons PA, Shamji AF, Schreiber SL. An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules. Cell 2013; 154:1151-61. PubMed
  • Corcoran RB, Rothenberg SM, Hata AN, Faber AC, Piris A, Nazarian RM, Brown RD, Godfrey JT, Winokur D, Walsh J, Mino-Kenudson M, Maheswaran S, Settleman J, Wargo JA, Flaherty KT, Haber DA, Engelman JA. TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma. Sci Transl Med 2013; 5:196ra98. PubMed
  • Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS. Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells. Nat Med 2013. PubMed
  • Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369:134-44. PubMed
  • Sullivan RJ, Lawrence DP, Wargo JA, Oh KS, Gonzalez RG, Piris A. Case records of the Massachusetts General Hospital. Case 21-2013. A 68-year-old man with metastatic melanoma. N Engl J Med 2013; 369:173-83. PubMed
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