Overcoming resistance to BRAF inhibition in BRAF-mutated metastatic melanoma

Oncotarget

Volumn 5, Issue 21, 2014, Pages 10206-10221

  Spagnolo, Francesco ^a   Ghiorzo, Paola ^a,b   Queirolo, Paola ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

BRAF; BRAF inhibitor; Dabrafenib; MEK inhibitor; Melanoma; Resistance; Vemurafenib

Indexed keywords

4 DIALLYLAMINOMETHYLENE 1,3,4,7,10,11,12,13,14,15,16,17 DODECAHYDRO 6 HYDROXY 1 METHOXYMETHYL 10,13 DIMETHYL 3,7,17 TRIOXO 2 OXACYCLOPENTA[A]PHENANTHREN 11 YL ACETATE; B RAF KINASE; B RAF KINASE INHIBITOR; BINIMETINIB; BUPARLISIB; CABOZANTINIB; COBIMETINIB; DABRAFENIB; DACTOLISIB; E 6201; EVEROLIMUS; HYDROXYCHLOROQUINE; IPILIMUMAB; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; MPDL 3280A; MSC 1936369B; OMIPALISIB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PICTILISIB; PROTEIN KINASE B; SAR 245409; SAR 260301; TEMSIROLIMUS; TRAMETINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; UPROSERTIB; VEMURAFENIB; XL 888; IMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; OXIME; SULFONAMIDE;

AEROBIC METABOLISM; ALTERNATIVE RNA SPLICING; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER IMMUNOTHERAPY; DRUG EFFICACY; DRUG RESISTANCE; ENZYME ACTIVATION; ENZYME INHIBITION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; METASTATIC MELANOMA; MITOCHONDRION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); GENETICS; MELANOMA; METASTASIS; MORTALITY; PRECLINICAL STUDY; RECURRENT DISEASE; SKIN NEOPLASMS;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, NEOPLASM; HUMANS; IMIDAZOLES; INDOLES; MELANOMA; NEOPLASM METASTASIS; OXIMES; PROTO-ONCOGENE PROTEINS B-RAF; RECURRENCE; SKIN NEOPLASMS; SULFONAMIDES;

EID: 84916897464     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2602     Document Type: Article

References (95)

1. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W. Mutations of the BRAF gene in human cancer. Nature 2002; 417(6892):949-954.
2. McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, Ribas A, Hogg D, Hamid O, Ascierto PA, Garbe C, Testori A, Maio M et al. Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014; 15(3):323-332.
3. Hauschild A, Grob J-J, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller Jr WH, Kaempgen E. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. The Lancet 2012; 380(9839):358-365.
4. Lito P, Rosen N, Solit DB. Tumor adaptation and resistance to RAF inhibitors. Nat. Med. 2013; 19(11):1401-1409.
5. Lito P, Pratilas CA, Joseph EW, Tadi M, Halilovic E, Zubrowski M, Huang A, Wong WL, Callahan MK, Merghoub T, Wolchok JD, de Stanchina E, Chandarlapaty S et al. Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas. Cancer Cell 2012; 22(5):668-682.
6. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010; 464(7287):427-430.
7. Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N. Engl. J. Med. 2012; 366(3):207-215.
8. Mendoza MC, Er EE, Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem. Sci. 2011; 36(6):320-328.
9. Britten CD. PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother. Pharmacol. 2013; 71(6):1395-1409.
10. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat J-P, Nickerson E, Auclair D, Li L, Place C, DiCara D, Ramos AH, Lawrence MS et al. A Landscape of Driver Mutations in Melanoma. Cell 2012; 150(2):251-263.
11. Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, Ariyan S, Narayan D, Dutton-Regester K et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat. Genet. 2012; 44(9):1006-1014.
12. Van Allen EM, Wagle N, Sucker A, Treacy DJ, Johannessen CM, Goetz EM, Place CS, Taylor-Weiner A, Whittaker S, Kryukov GV, Hodis E, Rosenberg M, McKenna A et al. The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma. Cancer Discov. 2014; 4(1):94-109.
13. Smalley KSM, Weber JS. Up Close and Personal: The Challenges of Precision Medicine in Melanoma. JNCI J. Natl. Cancer Inst. 2014; 106(2):djt443-djt443.
14. Paraiso KHT, Xiang Y, Rebecca VW, Abel EV, Chen YA, Munko AC, Wood E, Fedorenko IV, Sondak VK, Anderson ARA, Ribas A, Palma MD, Nathanson KL et al. PTEN Loss Confers BRAF Inhibitor Resistance to Melanoma Cells through the Suppression of BIM Expression. Cancer Res. 2011; 71(7):2750-2760.
15. Xing F, Persaud Y, Pratilas CA, Taylor BS, Janakiraman M, She QB, Gallardo H, Liu C, Merghoub T, Hefter B. Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring V600EBRAF. Oncogene 2012; 31(4):446-457.
16. Nathanson KL, Martin A-M, Wubbenhorst B, Greshock J, Letrero R, D'Andrea K, O'Day S, Infante JR, Falchook GS, Arkenau H-T, Millward M, Brown MP, Pavlick A et al. Tumor Genetic Analyses of Patients with Metastatic Melanoma Treated with the BRAF Inhibitor Dabrafenib (GSK2118436). Clin. Cancer Res. 2013; 19(17):4868-4878.
17. Shao Y, Aplin AE. Akt3-Mediated Resistance to Apoptosis in B-RAF-Targeted Melanoma Cells. Cancer Res. 2010; 70(16):6670-6681.
18. Trunzer K, Pavlick AC, Schuchter L, Gonzalez R, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Kim KB, Weber JS, Hersey P, Long GV, Lawrence D et al. Pharmacodynamic Effects and Mechanisms of Resistance to Vemurafenib in Patients With Metastatic Melanoma. J. Clin. Oncol. 2013; 31(14):1767-1774.
19. Smalley KS, Lioni M, Dalla Palma M, Xiao M, Desai B, Egyhazi S, Hansson J, Wu H, King AJ, Van Belle P. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol. Cancer Ther. 2008; 7(9):2876-2883.
20. Mar VJ, Wong SQ, Li J, Scolyer RA, McLean C, Papenfuss AT, Tothill RW, Kakavand H, Mann GJ, Thompson JF, Behren A, Cebon JS, Wolfe R et al. BRAF/NRAS Wild- Type Melanomas Have a High Mutation Load Correlating with Histologic and Molecular Signatures of UV Damage. Clin. Cancer Res. 2013; 19(17):4589-4598.
21. Gibney GT, Smalley KSM. An Unholy Alliance: Cooperation between BRAF and NF1 in Melanoma Development and BRAF Inhibitor Resistance. Cancer Discov. 2013; 3(3):260-263.
22. Whittaker SR, Theurillat J-P, Van Allen E, Wagle N, Hsiao J, Cowley GS, Schadendorf D, Root DE, Garraway LA. A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition. Cancer Discov. 2013; 3(3):350-362.
23. Maertens O, Johnson B, Hollstein P, Frederick DT, Cooper ZA, Messiaen L, Bronson RT, McMahon M, Granter S, Flaherty K, Wargo JA, Marais R, Cichowski K. Elucidating Distinct Roles for NF1 in Melanomagenesis. Cancer Discov. 2013; 3(3):338-349.
24. Nissan MH, Pratilas CA, Jones AM, Ramirez R, Won H, Liu C, Tiwari S, Kong L, Hanrahan AJ, Yao Z, Merghoub T, Ribas A, Chapman PB et al. Loss of NF1 in Cutaneous Melanoma Is Associated with RAS Activation and MEK Dependence. Cancer Res. 2014; 74(8):2340-2350.
25. Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, Emery CM, Stransky N, Cogdill AP, Barretina J, Caponigro G, Hieronymus H, Murray RR et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 2010; 468(7326):968-972.
26. Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 2012; 487(7408):505-509.
27. Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, Cooper ZA, Chapman PB, Solit DB et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 2012; 487(7408):500-504.
28. Spitz F, Gonzalez F, Peichel C, Vogt TF, Duboule D, Zákány J. Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations. Genes Dev. 2001; 15(17):2209-2214.
29. Shi H, Hugo W, Kong X, Hong A, Koya RC, Moriceau G, Chodon T, Guo R, Johnson DB, Dahlman KB, Kelley MC, Kefford RF, Chmielowski B et al. Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Cancer Discov. 2014; 4(1):80-93.
30. Menzies AM, Lum T, Wilmott JS, Hyman J, Kefford RF, Thompson JF, O'Toole S, Long GV, Scolyer RA. Intrapatient Homogeneity of BRAFV600E Expression in Melanoma. Am. J. Surg. Pathol. 2014.
31. Gowrishankar K, Snoyman S, Pupo GM, Becker TM, Kefford RF, Rizos H. Acquired resistance to BRAF inhibition can confer cross-resistance to combined BRAF/MEK inhibition. J. Invest. Dermatol. 2012; 132(7):1850-1859.
32. Rizos H, Menzies AM, Pupo GM, Carlino MS, Fung C, Hyman J, Haydu LE, Mijatov B, Becker TM, Boyd SC, Howle J, Saw R, Thompson JF et al. BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact. Clin. Cancer Res. 2014; 20(7):1965-1977.
33. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee M-K, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 2010; 468(7326):973-977.
34. Poulikakos PI, Rosen N. Mutant BRAF Melanomas- Dependence and Resistance. Cancer Cell 2011; 19(1):11-15.
35. Shi H, Kong X, Ribas A, Lo RS. Combinatorial Treatments That Overcome PDGFR -Driven Resistance of Melanoma Cells to V600EB-RAF Inhibition. Cancer Res. 2011; 71(15):5067-5074.
36. Sun C, Wang L, Huang S, Heynen GJJE, Prahallad A, Robert C, Haanen J, Blank C, Wesseling J, Willems SM, Zecchin D, Hobor S, Bajpe PK et al. Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 2014; 508(7494):118-122.
37. Girotti MR, Pedersen M, Sanchez-Laorden B, Viros A, Turajlic S, Niculescu-Duvaz D, Zambon A, Sinclair J, Hayes A, Gore M, Lorigan P, Springer C, Larkin J et al. Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma. Cancer Discov. 2013; 3(2):158-167.
38. Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, AtefiM, Titz B, Gabay MT, Salton M, Dahlman KB, Tadi M et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 2011; 480(7377):387-390.
39. 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 et al. MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition. Cancer Discov. 2014; 4(1):61-68.
40. Basile KJ, Le K, Hartsough EJ, Aplin AE. Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors. Pigment Cell Melanoma Res. 2014; 27(3):479-484.
41. Shi H, Moriceau G, Kong X, Lee M-K, Lee H, Koya RC, Ng C, Chodon T, Scolyer RA, Dahlman KB, Sosman JA, Kefford RF, Long GV et al. Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat. Commun. 2012; 3:724.
42. Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, Hamid O, Infante JR, Millward M, Pavlick AC, O'Day SJ, Blackman SC, Curtis CM et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. The Lancet 19; 379(9829):1893-1901.
43. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen CM, MacConaill LE, Hahn WC, Meyerson M, Garraway LA. Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling. J. Clin. Oncol. 2011; 29(22):3085-3096.
44. Shi H, Moriceau G, Kong X, Koya RC, Nazarian R, Pupo GM, Bacchiocchi A, Dahlman KB, Chmielowski B, Sosman JA, Halaban R, Kefford RF, Long GV et al. Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors. Cancer Discov. 2012; 2(5):414-424.
45. Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, Kim JJ, Hatton C, Chopra R, Oberholzer PA, Karpova MB. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc. Natl. Acad. Sci. 2009; 106(48):20411-20416.
46. Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, DiNunzio E et al. Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors. Cancer Discov. 2013; 3(7):742-750.
47. Hatzivassiliou G, Liu B, O'Brien C, Spoerke JM, Hoeflich KP, Haverty PM, Soriano R, Forrest WF, Heldens S, Chen H, Toy K, Ha C, Zhou W et al. ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors. Mol. Cancer Ther. 2012; 11(5):1143-1154.
48. Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, Stubbs H, Lee DY, Singh A. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res. 2008; 68(12):4853-4861.
49. Shi H, Hong A, Kong X, Koya RC, Song C, Moriceau G, Hugo W, Yu CC, Ng C, Chodon T, Scolyer RA, Kefford RF, Ribas A et al. A Novel AKT1 Mutant Amplifies an Adaptive Melanoma Response to BRAF Inhibition. Cancer Discov. 2014; 4(1):69-79.
50. Abel EV, Aplin AE. FOXD3 Is a Mutant B-RAF-Regulated Inhibitor of G1-S Progression in Melanoma Cells. Cancer Res. 2010; 70(7):2891-2900.
51. Basile KJ, Abel EV, Aplin AE. Adaptive upregulation of FOXD3 and resistance to PLX4032/4720-induced cell death in mutant B-RAF melanoma cells. Oncogene 2011; 31(19):2471-2479.
52. Abel EV, Basile KJ, Kugel CH, Witkiewicz AK, Le K, Amaravadi RK, Karakousis GC, Xu X, Xu W, Schuchter LM, Lee JB, Ertel A, Fortina P et al. Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J. Clin. Invest. 2013; 123(5):2155-2168.
53. Haq R, Yokoyama S, Hawryluk EB, Jonsson GB, Frederick DT, McHenry K, Porter D, Tran T-N, Love KT, Langer R, Anderson DG, Garraway LA, Duncan LM et al. BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. Proc. Natl. Acad. Sci. 2013; 110(11):4321-4326.
54. Corazao-Rozas P, Guerreschi P, Jendoubi M, André F, Jonneaux A, Scalbert C, Garçon G, Malet-Martino M, Balayssac S, Rocchi S, Savina A, Formstecher P, Mortier L et al. Mitochondrial oxidative stress is the Achille's heel of melanoma cells resistant to Braf-mutant inhibitor. Oncotarget. 2013; 4(11):1986-98.
55. Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, Körbel C, Laschke MW, Gimotty PA, Philipp SE, Krause E, Pätzold S, Villanueva J et al. Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells. Cancer Cell 2013; 23(6):811-825.
56. 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(7478):138-142.
57. Menzies AM, Long GV. Dabrafenib and Trametinib, Alone and in Combination for BRAF-Mutant Metastatic Melanoma. Clin. Cancer Res. 2014; 20(8):2035-2043.
58. Greger JG, Eastman SD, Zhang V, Bleam MR, Hughes AM, Smitheman KN, Dickerson SH, Laquerre SG, Liu L, Gilmer TM. Combinations of BRAF, MEK, and PI3K/mTOR Inhibitors Overcome Acquired Resistance to the BRAF Inhibitor GSK2118436 Dabrafenib, Mediated by NRAS or MEK Mutations. Mol. Cancer Ther. 2012; 11(4):909-920.
59. Sánchez-Hernández I, Baquero P, Calleros L, Chiloeches A. Dual inhibition of V600EBRAF and the PI3K/AKT/mTOR pathway cooperates to induce apoptosis in melanoma cells through a MEK-independent mechanism. Cancer Lett. 2012; 314(2):244-255.
60. Lassen A, AtefiM, Robert L, Wong DJ, Cerniglia M, Comin-Anduix B, Ribas A. Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanoma. Mol. Cancer 2014; 13(1):83.
61. Carlino MS, Todd JR, Gowrishankar K, Mijatov B, Pupo GM, Fung C, Snoyman S, Hersey P, Long GV, Kefford RF, Rizos H. Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma. Mol. Oncol. 2014; 8(3):544-554.
62. Bozic I, Reiter JG, Allen B, Antal T, Chatterjee K, Shah P, Moon YS, Yaqubie A, Kelly N, Le DT. Evolutionary dynamics of cancer in response to targeted combination therapy. Elife 2013.
63. Kirk R. Targeted therapies: The maths behind combination therapy. Nat. Rev. Clin. Oncol. 2013; 10(9):488-488.
64. Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, Fecher LA, Millward M, McArthur GA, Hwu P, Gonzalez R, Ott PA, Long GV et al. Phase II Study of the MEK1/MEK2 Inhibitor Trametinib in Patients With Metastatic BRAF-Mutant Cutaneous Melanoma Previously Treated With or Without a BRAF Inhibitor. J. Clin. Oncol. 2013; 31(4):482-489.
65. Romano E, Pradervand S, Paillusson A, Weber J, Harshman K, Muehlethaler K, Speiser D, Peters S, Rimoldi D, Michielin O. Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient with BRAFV600E-Mutated Cutaneous Melanoma Successfully Rechallenged after Progression. Clin. Cancer Res. 2013; 19(20):5749-5757.
66. Wilmott JS, Menzies AM, Haydu LE, Capper D, Preusser M, Zhang YE, Thompson JF, Kefford RF, von Deimling A, Scolyer RA, Long GV. BRAFV600E protein expression and outcome from BRAF inhibitor treatment in BRAFV600E metastatic melanoma. Br. J. Cancer 2013; 108(4):924-931.
67. Wilmott JS, Tembe V, Howle JR, Sharma R, Thompson JF, Rizos H, Lo RS, Kefford RF, Scolyer RA, Long GV. Intratumoral Molecular Heterogeneity in a BRAF-Mutant, BRAF Inhibitor-Resistant Melanoma: A Case Illustrating the Challenges for Personalized Medicine. Mol. Cancer Ther. 2012; 11(12):2704-2708.
68. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 2012; 366(10):883-892.
69. Griewank KG, Scolyer RA, Thompson JF, Flaherty KT, Schadendorf D, Murali R. Genetic Alterations and Personalized Medicine in Melanoma: Progress and Future Prospects. JNCI J. Natl. Cancer Inst. 2014; 106(2):djt435-djt435.
70. Rodic S, Mihalcioiu C, Saleh RR. Detection methods of circulating tumor cells in cutaneous melanoma: A systematic review. Crit. Rev. Oncol. Hematol. 2014. doi:10.1016/j.critrevonc.2014.01.007.
71. 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 et al. Isolation and Molecular Characterization of Circulating Melanoma Cells. Cell Rep. 2014; 7(3):645-653.
72. Chan MMK, Haydu LE, Menzies AM, Azer MWF, Klein O, Lyle M, Clements A, Guminski A, Kefford RF, Long GV. The nature and management of metastatic melanoma after progression on BRAF inhibitors: Effects of extended BRAF inhibition: BRAF Inhibitor Progression in Melanoma. Cancer 2014:n/a-n/a.
73. Thakur MD, Stuart DD. The Evolution of Melanoma Resistance Reveals Therapeutic Opportunities. Cancer Res. 2013; 73(20):6106-6110.
74. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 2013; 494(7436):251-255.
75. Thakur MD, Stuart DD. Molecular Pathways: Response and Resistance to BRAF and MEK Inhibitors in BRAFV600E Tumors. Clin. Cancer Res. 2014; 20(5):1074-1080.
76. Carlino MS, Gowrishankar K, Saunders CAB, Pupo GM, Snoyman S, Zhang XD, Saw R, Becker TM, Kefford RF, Long GV, Rizos H. Antiproliferative Effects of Continued Mitogen-Activated Protein Kinase Pathway Inhibition following Acquired Resistance to BRAF and/or MEK Inhibition in Melanoma. Mol. Cancer Ther. 2013; 12(7):1332-1342.
77. Hartsough EJ, Basile KJ, Aplin AE. Beneficial Effects of RAF Inhibitor in Mutant BRAF Splice Variant-Expressing Melanoma. Mol. Cancer Res. 2014; 12(5):795-802.
78. Seghers AC, Wilgenhof S, Lebbé C, Neyns B. Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor. Melanoma Res. 2012.
79. Abdel-Wahab O, Klimek VM, Gaskell AA, Viale A, Cheng D, Kim E, Rampal R, Bluth M, Harding JJ, Callahan MK, Merghoub T, Berger MF, Solit DB et al. Efficacy of Intermittent Combined RAF and MEK Inhibition in a Patient with Concurrent BRAF- and NRAS-Mutant Malignancies. Cancer Discov. 2014; 4(5):538-545.
80. Hong DS, Vence L, Falchook G, Radvanyi LG, Liu C, Goodman V, Legos JJ, Blackman S, Scarmadio A, Kurzrock R, Lizee G, Hwu P. BRAF(V600) Inhibitor GSK2118436 Targeted Inhibition of Mutant BRAF in Cancer Patients Does Not Impair Overall Immune Competency. Clin. Cancer Res. 2012; 18(8):2326-2335.
81. Comin-Anduix B, Chodon T, Sazegar H, Matsunaga D, Mock S, Jalil J, Escuin-Ordinas H, Chmielowski B, Koya RC, Ribas A. The Oncogenic BRAF Kinase Inhibitor PLX4032/RG7204 Does Not Affect the Viability or Function of Human Lymphocytes across a Wide Range of Concentrations. Clin. Cancer Res. 2010; 16(24):6040-6048.
82. Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, Mitra D, Boni A, Newton LP, Liu C, Peng W, Sullivan RJ, Lawrence DP et al. BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma. Clin. Cancer Res. 2013; 19(5):1225-1231.
83. Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw C-NJ, Sloss CM, Ferrone CR, Flaherty KT, Lawrence DP, Fisher DE, Tsao H, Wargo JA. Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function. Cancer Res. 2010; 70(13):5213-5219.
84. Liu C, Peng W, Xu C, Lou Y, Zhang M, Wargo JA, Chen JQ, Li HS, Watowich SS, Yang Y, Frederick DT, Cooper ZA, Mbofung RM et al. BRAF Inhibition Increases Tumor Infiltration by T cells and Enhances the Antitumor Activity of Adoptive Immunotherapy in Mice. Clin. Cancer Res. 2013; 19(2):393-403.
85. Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P, Scolyer RA. Selective BRAF Inhibitors Induce Marked T-cell Infiltration into Human Metastatic Melanoma. Clin. Cancer Res. 2012; 18(5):1386-1394.
86. 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 et al. Response to BRAF Inhibition in Melanoma Is Enhanced When Combined with Immune Checkpoint Blockade. Cancer Immunol. Res. 2014; 2(7):643-654.
87. Callahan MK, Masters G, Pratilas CA, Ariyan C, Katz J, Kitano S, Russell V, Gordon RA, Vyas S, Yuan J, Gupta A, Wigginton JM, Rosen N et al. Paradoxical Activation of T Cells via Augmented ERK Signaling Mediated by a RAF Inhibitor. Cancer Immunol. Res. 2014; 2(1):70-79.
88. 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(19):5283-5291.
89. Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with Combination of Vemurafenib and Ipilimumab. N. Engl. J. Med. 2013; 368(14):1365-1366.
90. Jiang X, Zhou J, Giobbie-Hurder A, Wargo J, Hodi FS. The Activation of MAPK in Melanoma Cells Resistant to BRAF Inhibition Promotes PD-L1 Expression That Is Reversible by MEK and PI3K Inhibition. Clin. Cancer Res. 2013; 19(3):598-609.
91. AtefiM, Avramis E, Lassen A, Wong DJL, Robert L, Foulad D, Cerniglia M, Titz B, Chodon T, Graeber TG, Comin-Anduix B, Ribas A. Effects of MAPK and PI3K Pathways on PD-L1 Expression in Melanoma. Clin. Cancer Res. 2014; 20(13):3446-3457.
92. Ascierto P, Grimaldi A, Acquavella N, Borgognoni L, Calabro L, Cascinelli N, Cesano A, Del Vecchio M, Eggermont A, Faries M, Ferrone S, Fox B, Gajewski T et al. Future perspectives in melanoma research. Meeting report from the "Melanoma Bridge. Napoli, December 2nd-4th 2012."J. Transl. Med. 2013; 11(1):137.
93. Ascierto PA, Margolin K. Ipilimumab before BRAF inhibitor treatment may be more beneficial than vice versa for the majority of patients with advanced melanoma. Cancer 2014; 120(11):1617-1619.
94. 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 et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer 2014; 120(11):1695-1701.
95. Blagosklonny MV. Why therapeutic response may not prolong the life of a cancer patient: selection for oncogenic resistance. Cell Cycle. 2005; 4(12):1693-8.