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Review Article

Evolution of Molecular Targets in Melanoma Treatment

Author(s): Khanh B. Tran, Christina M. Buchanan and Peter R. Shepherd*

Volume 26, Issue 4, 2020

Page: [396 - 414] Pages: 19

DOI: 10.2174/1381612826666200130091318

Price: $65

Abstract

Melanoma is the deadliest type of skin cancers, accounting for more than 80% of skin cancer mortality. Although melanoma was known very early in the history of medicine, treatment for this disease had remained largely the same until very recently. Previous treatment options, including removal surgery and systemic chemotherapy, offered little benefit in extending the survival of melanoma patients. However, the last decade has seen breakthroughs in melanoma treatment, which all emerged following new insight into the oncogenic signaling of melanoma. This paper reviewed the evolution of drug targets for melanoma treatment based on the emergence of novel findings in the molecular signaling of melanoma. One of the findings that are most influential in melanoma treatment is that more than 50% of melanoma tumors contain BRAF mutations. This is fundamental for the development of BRAF inhibitors, which is the first group of drugs that significantly improves the overall survival of melanoma patients compared to the traditional chemotherapeutic dacarbazine. More recently, findings of the role of immune checkpoint molecules such as CTLA-4 and PD1/PD-L1 in melanoma biology have led to the development of a new therapeutic category: immune checkpoint inhibitors, which, for the first time in the history of cancer treatment, produced a durable response in a subset of melanoma patients. However, as this paper discussed next, there is still an unmet need for melanoma treatment. A significant population of patients did not respond to either BRAF inhibitors or immune checkpoint inhibitors. Of those patients who gained an initial response from those therapies, a remarkable percentage would develop drug resistance even when MEK inhibitors were added to the treatment. Finally, this paper discusses some possible targets for melanoma treatment.

Keywords: BRAF, MEK, immunotherapy, clinical trials, melanoma, immune checkpoint molecules.

« Previous Next »
[1]
McCormick F. ras GTPase activating protein: signal transmitter and signal terminator. Cell 1989; 56(1): 5-8.
[http://dx.doi.org/10.1016/0092-8674(89)90976-8] [PMID: 2535967]
[2]
Downward J. Ras signalling and apoptosis. Curr Opin Genet Dev 1998; 8(1): 49-54.
[http://dx.doi.org/10.1016/S0959-437X(98)80061-0] [PMID: 9529605]
[3]
Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003; 3(1): 11-22.
[http://dx.doi.org/10.1038/nrc969] [PMID: 12509763]
[4]
Stevens CW, Manoharan TH, Fahl WE. Characterization of mutagen-activated cellular oncogenes that confer anchorage independence to human fibroblasts and tumorigenicity to NIH 3T3 cells: sequence analysis of an enzymatically amplified mutant HRAS allele. Proc Natl Acad Sci USA 1988; 85(11): 3875-9.
[http://dx.doi.org/10.1073/pnas.85.11.3875] [PMID: 3131765]
[5]
Yuasa Y, Gol RA, Chang A, et al. Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells. Proc Natl Acad Sci USA 1984; 81(12): 3670-4.
[http://dx.doi.org/10.1073/pnas.81.12.3670 ] [PMID: 6587382]
[6]
Poynter JN, Elder JT, Fullen DR, et al. BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res 2006; 16(4): 267-73.
[http://dx.doi.org/10.1097/01.cmr.0000222600.73179.f3] [PMID: 16845322]
[7]
Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353(20): 2135-47.
[http://dx.doi.org/10.1056/NEJMoa050092] [PMID: 16291983]
[8]
Goel VK, Lazar AJ, Warneke CL, Redston MS, Haluska FG. Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma. J Invest Dermatol 2006; 126(1): 154-60.
[http://dx.doi.org/10.1038/sj.jid.5700026] [PMID: 16417231]
[9]
Muñoz-Couselo E, Adelantado EZ, Ortiz C, García JS, Perez-Garcia J. NRAS-mutant melanoma: current challenges and future prospect. OncoTargets Ther 2017; 10: 3941-7.
[http://dx.doi.org/10.2147/OTT.S117121] [PMID: 28860801]
[10]
Padua RA, Barrass N, Currie GA. A novel transforming gene in a human malignant melanoma cell line. Nature 1984; 311(5987): 671-3.
[http://dx.doi.org/10.1038/311671a0] [PMID: 6090953]
[11]
van ’t Veer LJ, Burgering BM, Versteeg R, et al. N-ras mutations in human cutaneous melanoma from sun-exposed body sites. Mol Cell Biol 1989; 9(7): 3114-6.
[http://dx.doi.org/10.1128/MCB.9.7.3114] [PMID: 2674680]
[12]
Jiveskog S, Ragnarsson-Olding B, Platz A, Ringborg U. N-ras mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin. J Invest Dermatol 1998; 111(5): 757-61.
[http://dx.doi.org/10.1046/j.1523-1747.1998.00376.x] [PMID: 9804334]
[13]
Cancer Genome Atlas N. Cancer genome atlas network. genomic classification of cutaneous melanoma. Cell 2015; 161(7): 1681-96.
[http://dx.doi.org/10.1016/j.cell.2015.05.044] [PMID: 26091043]
[14]
Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417(6892): 949-54.
[http://dx.doi.org/10.1038/nature00766] [PMID: 12068308]
[15]
Rubinstein JC, Sznol M, Pavlick AC, et al. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med 2010; 8: 67-7.
[http://dx.doi.org/10.1186/1479-5876-8-67] [PMID: 20630094]
[16]
Menzies AM, Haydu LE, Visintin L, et al. Distinguishing clinicopathologic features of patients with V600E and V600K BRAF-mutant metastatic melanoma. Clin Cancer Res 2012; 18(12): 3242-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0052] [PMID: 22535154]
[17]
Heinzerling L, Kühnapfel S, Meckbach D, et al. Rare BRAF mutations in melanoma patients: implications for molecular testing in clinical practice. Br J Cancer 2013; 108(10): 2164-71.
[http://dx.doi.org/10.1038/bjc.2013.143] [PMID: 23579220]
[18]
Klein O, Clements A, Menzies AM, O’Toole S, Kefford RF, Long GV. BRAF inhibitor activity in V600R metastatic melanoma. Eur J Cancer 2013; 49(5): 1073-9.
[http://dx.doi.org/10.1016/j.ejca.2012.11.004] [PMID: 23237741]
[19]
McArthur GA, Chapman PB, Robert C, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 2014; 15(3): 323-32.
[http://dx.doi.org/10.1016/S1470-2045(14)70012-9] [PMID: 24508103]
[20]
Ascierto PA, Minor D, Ribas A, et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol 2013; 31(26): 3205-11.
[http://dx.doi.org/10.1200/JCO.2013.49.8691] [PMID: 23918947]
[21]
Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380(9839): 358-65.
[http://dx.doi.org/10.1016/S0140-6736(12)60868-X] [PMID: 22735384]
[22]
John M. Kirkwood , Georgina V Long , Uwe Trefzer, et al. BREAK-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets). J Clin Oncol 2012; 30(15): 8501-1.
[23]
McArthur GA, Maio M, Arance A, et al. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol 2017; 28(3): 634-41.
[PMID: 27993793]
[24]
Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol Res 2019; 144: 19-50.
[http://dx.doi.org/10.1016/j.phrs.2019.03.006] [PMID: 30877063]
[25]
Kim G, McKee AE, Ning YM, et al. FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation. Clin Cancer Res 2014; 20(19): 4994-5000.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0776] [PMID: 25096067]
[26]
Ballantyne AD, Garnock-Jones KP. Dabrafenib: first global approval. Drugs 2013; 73(12): 1367-76.
[http://dx.doi.org/10.1007/s40265-013-0095-2] [PMID: 23881668]
[27]
Odogwu L, Mathieu L, Blumenthal G, et al. FDA Approval Summary: dabrafenib and trametinib for the treatment of metastatic non-small cell lung cancers harboring BRAF V600E mutations. Oncologist 2018; 23(6): 740-5.
[http://dx.doi.org/10.1634/theoncologist.2017-0642] [PMID: 29438093]
[28]
Kirkwood JM, Bastholt L, Robert C, et al. Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin Cancer Res 2012; 18(2): 555-67.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1491] [PMID: 22048237]
[29]
Carvajal RD, Sosman JA, Quevedo JF, et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA 2014; 311(23): 2397-405.
[http://dx.doi.org/10.1001/jama.2014.6096] [PMID: 24938562]
[30]
Robert C, Dummer R, Gutzmer R, et al. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol 2013; 14(8): 733-40.
[http://dx.doi.org/10.1016/S1470-2045(13)70237-7] [PMID: 23735514]
[31]
Dummer R, Schadendorf D, Ascierto PA, et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2017; 18(4): 435-45.
[http://dx.doi.org/10.1016/S1470-2045(17)30180-8] [PMID: 28284557]
[32]
Shi H, Hong A, Kong X, et al. A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition. Cancer Discov 2014; 4(1): 69-79.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0279] [PMID: 24265152]
[33]
Shi H, Hugo W, Kong X, et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 2014; 4(1): 80-93.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0642] [PMID: 24265155]
[34]
Van Allen EM, Wagle N, Sucker A, et al. Dermatologic cooperative oncology group of germany (DeCOG). The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014; 4(1): 94-109.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0617] [PMID: 24265153]
[35]
Ascierto PA, McArthur GA, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016; 17(9): 1248-60.
[http://dx.doi.org/10.1016/S1470-2045(16)30122-X] [PMID: 27480103]
[36]
Grob JJ, Amonkar MM, Karaszewska B, et al. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial. Lancet Oncol 2015; 16(13): 1389-98.
[http://dx.doi.org/10.1016/S1470-2045(15)00087-X] [PMID: 26433819]
[37]
Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 2019; 381(7): 626-36.
[http://dx.doi.org/10.1056/NEJMoa1904059] [PMID: 31166680]
[38]
Long GV, Flaherty KT, Stroyakovskiy D, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol 2017; 28(7): 1631-9.
[http://dx.doi.org/10.1093/annonc/mdx176] [PMID: 28475671]
[39]
Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2018; 19(5): 603-15.
[http://dx.doi.org/10.1016/S1470-2045(18)30142-6] [PMID: 29573941]
[40]
Maio M, Lewis K, Demidov L, et al. BRIM8 Investigators. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol 2018; 19(4): 510-20.
[http://dx.doi.org/10.1016/S1470-2045(18)30106-2] [PMID: 29477665]
[41]
Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 2017; 377(19): 1813-23.
[http://dx.doi.org/10.1056/NEJMoa1708539] [PMID: 28891408]
[42]
Sharpe M, Mount N. Genetically modified T cells in cancer therapy: opportunities and challenges. Dis Model Mech 2015; 8(4): 337-50.
[http://dx.doi.org/10.1242/dmm.018036] [PMID: 26035842]
[43]
Bonaventura P, Shekarian T, Alcazer V, et al. Cold tumors: a therapeutic challenge for immunotherapy. Front Immunol 2019; 10(168): 168.
[http://dx.doi.org/10.3389/fimmu.2019.00168] [PMID: 30800125]
[44]
Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018; 50(12): 165.
[http://dx.doi.org/10.1038/s12276-018-0191-1] [PMID: 30546008]
[45]
Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 2015; 27(4): 450-61.
[http://dx.doi.org/10.1016/j.ccell.2015.03.001] [PMID: 25858804]
[46]
Chapman PB, Hauschild A, Robert C, et al. BRIM-3 study group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364(26): 2507-16.
[http://dx.doi.org/10.1056/NEJMoa1103782] [PMID: 21639808]
[47]
Chapman PB, Robert C, Larkin J, et al. Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. Ann Oncol 2017; 28(10): 2581-7.
[http://dx.doi.org/10.1093/annonc/mdx339] [PMID: 28961848]
[48]
Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371(20): 1867-76.
[http://dx.doi.org/10.1056/NEJMoa1408868] [PMID: 25265494]
[49]
Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015; 372(1): 30-9.
[http://dx.doi.org/10.1056/NEJMoa1412690] [PMID: 25399551]
[50]
Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014; 371(20): 1877-88.
[http://dx.doi.org/10.1056/NEJMoa1406037] [PMID: 25265492]
[51]
Maio M, Grob JJ, Aamdal S, et al. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol 2015; 33(10): 1191-6.
[http://dx.doi.org/10.1200/JCO.2014.56.6018] [PMID: 25713437]
[52]
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364(26): 2517-26.
[http://dx.doi.org/10.1056/NEJMoa1104621] [PMID: 21639810]
[53]
Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363(8): 711-23.
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[54]
McDermott D, Haanen J, Chen TT, Lorigan P, O’Day S. MDX010-20 Investigators. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol 2013; 24(10): 2694-8.
[http://dx.doi.org/10.1093/annonc/mdt291] [PMID: 23942774]
[55]
Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372(4): 320-30.
[http://dx.doi.org/10.1056/NEJMoa1412082] [PMID: 25399552]
[56]
Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015; 16(4): 375-84.
[http://dx.doi.org/10.1016/S1470-2045(15)70076-8] [PMID: 25795410]
[57]
Larkin J, Minor D, D’Angelo S, et al. Overall survival in patients with advanced melanoma who received nivolumab versus investigator’s choice chemotherapy in checkmate 037: a randomized, controlled, open-label phase III trial. J Clin Oncol 2018; 36(4): 383-90.
[http://dx.doi.org/10.1200/JCO.2016.71.8023] [PMID: 28671856]
[58]
Robert C, Ribas A, Schachter J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol 2019; 20(9): 1239-51.
[http://dx.doi.org/10.1016/S1470-2045(19)30388-2] [PMID: 31345627]
[59]
Weber JS, Gibney G, Sullivan RJ, et al. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. Lancet Oncol 2016; 17(7): 943-55.
[http://dx.doi.org/10.1016/S1470-2045(16)30126-7] [PMID: 27269740]
[60]
Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 2018; 19(11): 1480-92.
[http://dx.doi.org/10.1016/S1470-2045(18)30700-9] [PMID: 30361170]
[61]
Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001; 19(1): 565-94.
[http://dx.doi.org/10.1146/annurev.immunol.19.1.565] [PMID: 11244047]
[62]
Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995; 270(5238): 985-8.
[http://dx.doi.org/10.1126/science.270.5238.985] [PMID: 7481803]
[63]
Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995; 3(5): 541-7.
[http://dx.doi.org/10.1016/1074-7613(95)90125-6] [PMID: 7584144]
[64]
Kündig TM, Shahinian A, Kawai K, et al. Duration of TCR stimulation determines costimulatory requirement of T cells. Immunity 1996; 5(1): 41-52.
[http://dx.doi.org/10.1016/S1074-7613(00)80308-8] [PMID: 8758893]
[65]
Shahinian A, Pfeffer K, Lee KP, et al. Differential T cell costimulatory requirements in CD28-deficient mice. Science 1993; 261(5121): 609-12.
[http://dx.doi.org/10.1126/science.7688139] [PMID: 7688139]
[66]
Borriello F, Sethna MP, Boyd SD, et al. B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity 1997; 6(3): 303-13.
[http://dx.doi.org/10.1016/S1074-7613(00)80333-7] [PMID: 9075931]
[67]
Greene JL, Leytze GM, Emswiler J, et al. Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions. J Biol Chem 1996; 271(43): 26762-71.
[http://dx.doi.org/10.1074/jbc.271.43.26762] [PMID: 8900156]
[68]
Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 1991; 174(3): 561-9.
[http://dx.doi.org/10.1084/jem.174.3.561] [PMID: 1714933]
[69]
Ribas A, Kefford R, Marshall MA, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol 2013; 31(5): 616-22.
[http://dx.doi.org/10.1200/JCO.2012.44.6112] [PMID: 23295794]
[70]
Ascierto PA, Del Vecchio M, Robert C, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 2017; 18(5): 611-22.
[http://dx.doi.org/10.1016/S1470-2045(17)30231-0] [PMID: 28359784]
[71]
Eggermont AMM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 2016; 375(19): 1845-55.
[http://dx.doi.org/10.1056/NEJMoa1611299] [PMID: 27717298]
[72]
Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 2008; 8(6): 467-77.
[http://dx.doi.org/10.1038/nri2326] [PMID: 18500231]
[73]
Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 2015; 16(8): 908-18.
[http://dx.doi.org/10.1016/S1470-2045(15)00083-2] [PMID: 26115796]
[74]
Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018; 378(19): 1789-801.
[http://dx.doi.org/10.1056/NEJMoa1802357] [PMID: 29658430]
[75]
Robert C, Schachter J, Long GV, et al. KEYNOTE-006 investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372(26): 2521-32.
[http://dx.doi.org/10.1056/NEJMoa1503093] [PMID: 25891173]
[76]
Weber J, Mandala M, Del Vecchio M, et al. CheckMate 238 Collaborators. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017; 377(19): 1824-35.
[http://dx.doi.org/10.1056/NEJMoa1709030] [PMID: 28891423]
[77]
Long GV, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 2018; 19(5): 672-81.
[http://dx.doi.org/10.1016/S1470-2045(18)30139-6] [PMID: 29602646]
[78]
Flaherty KT, Robert C, Hersey P, et al. METRIC study group. improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012; 367(2): 107-14.
[http://dx.doi.org/10.1056/NEJMoa1203421] [PMID: 22663011]
[79]
Jakob JA, Bassett RL Jr, Ng CS, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 2012; 118(16): 4014-23.
[http://dx.doi.org/10.1002/cncr.26724] [PMID: 22180178]
[80]
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443-54.
[http://dx.doi.org/10.1056/NEJMoa1200690] [PMID: 22658127]
[81]
Lugowska I, Koseła-Paterczyk H, Kozak K, Rutkowski P. Trametinib: a MEK inhibitor for management of metastatic melanoma. OncoTargets Ther 2015; 8: 2251-9.
[PMID: 26347206]
[82]
Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363(9): 809-19.
[http://dx.doi.org/10.1056/NEJMoa1002011] [PMID: 20818844]
[83]
R. Kefford, H. Arkenau, M.P. Brown, et al. Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. J Clin Oncol 2010; 28(15): 8503.
[84]
Shi H, Moriceau G, Kong X, et al. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun 2012; 3(724): 724.
[http://dx.doi.org/10.1038/ncomms1727] [PMID: 22395615]
[85]
Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 2010; 468(7326): 973-7.
[http://dx.doi.org/10.1038/nature09626] [PMID: 21107323]
[86]
Wagle N, Emery C, Berger MF, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol 2011; 29(22): 3085-96.
[http://dx.doi.org/10.1200/JCO.2010.33.2312] [PMID: 21383288]
[87]
Shi H, Kong X, Ribas A, Lo RS. Combinatorial treatments that overcome PDGFRβ-driven resistance of melanoma cells to V600EB-RAF inhibition. Cancer Res 2011; 71(15): 5067-74.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0140] [PMID: 21803746]
[88]
Villanueva J, Vultur A, Lee JT, et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell 2010; 18(6): 683-95.
[http://dx.doi.org/10.1016/j.ccr.2010.11.023] [PMID: 21156289]
[89]
Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 2010; 468(7326): 968-72.
[http://dx.doi.org/10.1038/nature09627] [PMID: 21107320]
[90]
Pitt JM, Vétizou M, Daillère R, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity 2016; 44(6): 1255-69.
[http://dx.doi.org/10.1016/j.immuni.2016.06.001] [PMID: 27332730]
[91]
O’Donnell JS, Long GV, Scolyer RA, Teng MW, Smyth MJ. Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev 2017; 52: 71-81.
[http://dx.doi.org/10.1016/j.ctrv.2016.11.007] [PMID: 27951441]
[92]
Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017; 168(4): 707-23.
[http://dx.doi.org/10.1016/j.cell.2017.01.017] [PMID: 28187290]
[93]
Thommen DS, Schreiner J, Müller P, et al. Progression of lung cancer is associated with increased dysfunction of T cells defined by coexpression of multiple inhibitory receptors. Cancer Immunol Res 2015; 3(12): 1344-55.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0097] [PMID: 26253731]
[94]
Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med 2013; 210(7): 1389-402.
[http://dx.doi.org/10.1084/jem.20130066] [PMID: 23752227]
[95]
Spranger S, Koblish HK, Horton B, Scherle PA, Newton R, Gajewski TF. Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. J Immunother Cancer 2014; 2(1): 3.
[http://dx.doi.org/10.1186/2051-1426-2-3] [PMID: 24829760]
[96]
Davis ME, Zuckerman JE, Choi CH, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010; 464(7291): 1067-70.
[http://dx.doi.org/10.1038/nature08956] [PMID: 20305636]
[97]
Michaelson D, Ali W, Chiu VK, et al. Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases. Mol Biol Cell 2005; 16(4): 1606-16.
[http://dx.doi.org/10.1091/mbc.e04-11-0960] [PMID: 15659645]
[98]
Choy E, Chiu VK, Silletti J, et al. Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi. Cell 1999; 98(1): 69-80.
[http://dx.doi.org/10.1016/S0092-8674(00)80607-8] [PMID: 10412982]
[99]
Wang J, Yao X, Huang J. New tricks for human farnesyltransferase inhibitor: cancer and beyond. MedChemComm 2017; 8(5): 841-54.
[http://dx.doi.org/10.1039/C7MD00030H] [PMID: 30108801]
[100]
Alan LH, Nicole GC, Deborah JLW, et al. An open-label, phase II study of tipifarnib for the treatment of HRAS mutant solid tumors, including squamous cell carcinomas of the head and neck. J Clin Oncol 2017; 35(15) TPS2618
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.TPS2618]
[101]
Shi B, Yaremko B, Hajian G, et al. The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumor activity in vivo. Cancer Chemother Pharmacol 2000; 46(5): 387-93.
[http://dx.doi.org/10.1007/s002800000170] [PMID: 11127943]
[102]
Moasser MM, Sepp-Lorenzino L, Kohl NE, et al. Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones. Proc Natl Acad Sci USA 1998; 95(4): 1369-74.
[http://dx.doi.org/10.1073/pnas.95.4.1369] [PMID: 9465021]
[103]
Van Cutsem E, van de Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004; 22(8): 1430-8.
[http://dx.doi.org/10.1200/JCO.2004.10.112] [PMID: 15084616]
[104]
Sparano JA, Moulder S, Kazi A, et al. Phase II trial of tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer. Clin Cancer Res 2009; 15(8): 2942-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2658] [PMID: 19351752]
[105]
Johnston SRD, Semiglazov VF, Manikhas GM, et al. A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. Breast Cancer Res Treat 2008; 110(2): 327-35.
[http://dx.doi.org/10.1007/s10549-007-9726-1] [PMID: 17851757]
[106]
Mohammed I, Hampton SE, Ashall L, et al. 8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells. Bioorg Med Chem 2016; 24(2): 160-78.
[http://dx.doi.org/10.1016/j.bmc.2015.11.043] [PMID: 26706114]
[107]
Marín-Ramos NI, Balabasquer M, Ortega-Nogales FJ, et al. A potent isoprenylcysteine carboxylmethyltransferase (ICMT) inhibitor improves survival in ras-driven acute myeloid leukemia. J Med Chem 2019; 62(13): 6035-46.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00145] [PMID: 31181882]
[108]
Simpson L, Parsons R. PTEN: life as a tumor suppressor. Exp Cell Res 2001; 264(1): 29-41.
[http://dx.doi.org/10.1006/excr.2000.5130] [PMID: 11237521]
[109]
Aguissa-Touré AH, Li G. Genetic alterations of PTEN in human melanoma. Cell Mol Life Sci 2012; 69(9): 1475-91.
[http://dx.doi.org/10.1007/s00018-011-0878-0] [PMID: 22076652]
[110]
Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997; 275(5300): 661-5.
[http://dx.doi.org/10.1126/science.275.5300.661] [PMID: 9005851]
[111]
Ramaswamy S, Nakamura N, Vazquez F, et al. Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci USA 1999; 96(5): 2110-5.
[http://dx.doi.org/10.1073/pnas.96.5.2110] [PMID: 10051603]
[112]
Tsao H, Goel V, Wu H, Yang G, Haluska FG. Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J Invest Dermatol 2004; 122(2): 337-41.
[http://dx.doi.org/10.1046/j.0022-202X.2004.22243.x] [PMID: 15009714]
[113]
Brognard J, Sierecki E, Gao T, Newton AC. PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell 2007; 25(6): 917-31.
[http://dx.doi.org/10.1016/j.molcel.2007.02.017] [PMID: 17386267]
[114]
Janku F, Lee JJ, Tsimberidou AM, et al. PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. PLoS One 2011; 6(7): e22769-9.
[http://dx.doi.org/10.1371/journal.pone.0022769] [PMID: 21829508]
[115]
Davies MA, Stemke-Hale K, Tellez C, et al. A novel AKT3 mutation in melanoma tumours and cell lines. Br J Cancer 2008; 99(8): 1265-8.
[http://dx.doi.org/10.1038/sj.bjc.6604637] [PMID: 18813315]
[116]
Soulières D, Faivre S, Mesía R, et al. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Oncol 2017; 18(3): 323-35.
[http://dx.doi.org/10.1016/S1470-2045(17)30064-5] [PMID: 28131786]
[117]
Meier FE, et al. An open-label, uncontrolled, single arm phase II trial of the PI3K inhibitor buparlisib in patients with melanoma brain metastases. J Clin Oncol 2017; 35(15)TPS9595
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.TPS9595]
[118]
Ando Y, Iwasa S, Takahashi S, et al. Phase I study of alpelisib (BYL719), an α-specific PI3K inhibitor, in Japanese patients with advanced solid tumors. Cancer Sci 2019; 110(3): 1021-31.
[http://dx.doi.org/10.1111/cas.13923] [PMID: 30588709]
[119]
André F, Ciruelos E, Rubovszky G, et al. SOLAR-1 study group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 2019; 380(20): 1929-40.
[http://dx.doi.org/10.1056/NEJMoa1813904] [PMID: 31091374]
[120]
Find NCI-Supported Clinical Trials. Available at: https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2018-01609&r=1
[121]
Mateo J, Ganji G, Lemech C, et al. A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2017; 23(19): 5981-92.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0725] [PMID: 28645941]
[122]
Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res 2014; 2(9): 823-30.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0112] [PMID: 25187272]
[123]
Lancaster GI, Skiba B, Yang C, et al. IκB kinase β (IKKβ) does not mediate feedback inhibition of the insulin signalling cascade. Biochem J 2012; 442(3): 723-32.
[http://dx.doi.org/10.1042/BJ20112037] [PMID: 22364283]
[124]
Hernández-Rodas MC, Valenzuela R, Echeverría F, et al. Supplementation with docosahexaenoic acid and extra virgin olive oil prevents liver steatosis induced by a high-fat diet in mice through PPAR-α and Nrf2 upregulation with concomitant SREBP-1c and NF-kB downregulation. Mol Nutr Food Res 2017; 61(12)201700479
[http://dx.doi.org/10.1002/mnfr.201700479] [PMID: 28940752]
[125]
Park MH, Hong JT. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells 2016; 5(2): 15.
[http://dx.doi.org/10.3390/cells5020015] [PMID: 27043634]
[126]
Bai D, Ueno L, Vogt PK. Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. Int J Cancer 2009; 125(12): 2863-70.
[http://dx.doi.org/10.1002/ijc.24748] [PMID: 19609947]
[127]
Haller D, Russo MP, Sartor RB, Jobin C. IKK β and phosphatidylinositol 3-kinase/Akt participate in non-pathogenic Gram-negative enteric bacteria-induced RelA phosphorylation and NF-κ B activation in both primary and intestinal epithelial cell lines. J Biol Chem 2002; 277(41): 38168-78.
[http://dx.doi.org/10.1074/jbc.M205737200] [PMID: 12140289]
[128]
Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 2018; 18(5): 309-24.
[http://dx.doi.org/10.1038/nri.2017.142] [PMID: 29379212]
[129]
Valenzuela R, Illesca P, Echeverría F, et al. Molecular adaptations underlying the beneficial effects of hydroxytyrosol in the pathogenic alterations induced by a high-fat diet in mouse liver: PPAR-α and Nrf2 activation, and NF-κB down-regulation. Food Funct 2017; 8(4): 1526-37.
[http://dx.doi.org/10.1039/C7FO00090A] [PMID: 28386616]
[130]
Ahmad A, Biersack B, Li Y, et al. Targeted regulation of PI3K/Akt/mTOR/NF-κB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy. Anticancer Agents Med Chem 2013; 13(7): 1002-13.
[http://dx.doi.org/10.2174/18715206113139990078] [PMID: 23272910]
[131]
Li B, Xi P, Wang Z, et al. PI3K/Akt/mTOR signaling pathway participates in Streptococcus uberis-induced inflammation in mammary epithelial cells in concert with the classical TLRs/NF-ĸB pathway. Vet Microbiol 2018; 227: 103-11.
[http://dx.doi.org/10.1016/j.vetmic.2018.10.031] [PMID: 30473339]
[132]
Dan HC, Cooper MJ, Cogswell PC, Duncan JA, Ting JP, Baldwin AS. Akt-dependent regulation of NF-κB is controlled by mTOR and Raptor in association with IKK. Genes Dev 2008; 22(11): 1490-500.
[http://dx.doi.org/10.1101/gad.1662308] [PMID: 18519641]
[133]
Kong Y, Si L, Li Y, et al. Analysis of mTOR gene aberrations in melanoma patients and evaluation of their sensitivity to PI3K-AKT-mTOR pathway inhibitors. Clin Cancer Res 2016; 22(4): 1018-27.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1110] [PMID: 26490311]
[134]
Bendell JC, Kurkjian C, Infante JR, et al. A phase 1 study of the sachet formulation of the oral dual PI3K/mTOR inhibitor BEZ235 given twice daily (BID) in patients with advanced solid tumors. Invest New Drugs 2015; 33(2): 463-71.
[http://dx.doi.org/10.1007/s10637-015-0218-6] [PMID: 25707361]
[135]
Buchanan CM, Lee KL, Shepherd PR. For better or worse: the potential for dose limiting the on-target toxicity of PI 3-kinase inhibitors. Biomolecules 2019; 9(9): 402.
[http://dx.doi.org/10.3390/biom9090402] [PMID: 31443495]
[136]
Gamage SA, Spicer JA, Tsang KY, et al. Synthesis and evaluation of imidazo1,2-apyridine analogues of the ZSTK474 class of phosphatidylinositol 3-kinase inhibitors. Chem Asian J 2019; 14(8): 1249-61.
[http://dx.doi.org/10.1002/asia.201801762] [PMID: 30714356]
[137]
Giddens AC, Gamage SA, Kendall JD, et al. Synthesis and biological evaluation of solubilized sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474. Bioorg Med Chem 2019; 27(8): 1529-45.
[http://dx.doi.org/10.1016/j.bmc.2019.02.050] [PMID: 30850264]
[138]
Wang J, Gong GQ, Zhou Y, et al. High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds. Acta Pharmacol Sin 2018; 39(11): 1816-22.
[http://dx.doi.org/10.1038/s41401-018-0057-z] [PMID: 29991713]
[139]
Rewcastle GW, Kolekar S, Buchanan CM, et al. Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kα, in comparison to established pan PI3K inhibitors. Oncotarget 2017; 8(29): 47725-40.
[http://dx.doi.org/10.18632/oncotarget.17730] [PMID: 28537878]
[140]
Casey PJ, Seabra MC. Protein prenyltransferases. J Biol Chem 1996; 271(10): 5289-92.
[http://dx.doi.org/10.1074/jbc.271.10.5289] [PMID: 8621375]
[141]
Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343(6257): 425-30.
[http://dx.doi.org/10.1038/343425a0] [PMID: 1967820]
[142]
Marshall CJ. Protein prenylation: a mediator of protein-protein interactions. Science 1993; 259(5103): 1865-6.
[http://dx.doi.org/10.1126/science.8456312] [PMID: 8456312]
[143]
Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65(1): 241-69.
[http://dx.doi.org/10.1146/annurev.bi.65.070196.001325] [PMID: 8811180]
[144]
Berg JM. Cholesterol is synthesized from acetyl coenzyme a in three stagesbiochemistry. 5th ed. New York: W H Freeman 2002.
[145]
KB. Tran, S. Kolekar, SMF. Jamieson, et al. 412P Effects of statins on melanoma. Annals of Oncology 2016; 279.
[146]
Tran K, Francis WH, Stephen MFJ, et al. Preclinical efficacy and sensitivity determinants of statins in molecularly-defined models of melanoma Conference paper New Zealand Society for Oncology Conference. Available at:https://www.researchgate.net/publication/326981611
[147]
Miziorko HM. Enzymes of the mevalonate pathway of isoprenoid biosynthesis. Arch Biochem Biophys 2011; 505(2): 131-43.
[http://dx.doi.org/10.1016/j.abb.2010.09.028] [PMID: 20932952]
[148]
Tobert JA. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov 2003; 2(7): 517-26.
[http://dx.doi.org/10.1038/nrd1112] [PMID: 12815379]
[149]
Kuzuyama T, Seto H. Two distinct pathways for essential metabolic precursors for isoprenoid biosynthesis. Proc Jpn Acad, Ser B, Phys Biol Sci 2012; 88(3): 41-52.
[http://dx.doi.org/10.2183/pjab.88.41] [PMID: 22450534]
[150]
Murtola TJ, Visvanathan K, Artama M, Vainio H, Pukkala E. Statin use and breast cancer survival: a nationwide cohort study from Finland. PLoS One 2014; 9(10) e110231
[http://dx.doi.org/10.1371/journal.pone.0110231] [PMID: 25329299 ]
[151]
Desai P, Lehman A, Chlebowski RT, et al. Statins and breast cancer stage and mortality in the women’s health initiative. Cancer Causes Control 2015; 26(4): 529-39.
[http://dx.doi.org/10.1007/s10552-015-0530-7 ] [PMID: 25736184]
[152]
Cardwell CR, Hicks BM, Hughes C, Murray LJ. Statin use after diagnosis of breast cancer and survival: a population-based cohort study. Epidemiology 2015; 26(1): 68-78.
[http://dx.doi.org/10.1097/EDE.0000000000000189] [PMID: 25304447]
[153]
Yu O, Eberg M, Benayoun S, et al. Use of statins and the risk of death in patients with prostate cancer. J Clin Oncol 2014; 32(1): 5-11.
[http://dx.doi.org/10.1200/JCO.2013.49.4757] [PMID: 24190110]
[154]
Voorneveld PW, Reimers MS, Bastiaannet E, et al. Statin use after diagnosis of colon cancer and patient survival Gastroenterology 2017; 153(2): 470-479 e4
[http://dx.doi.org/10.1053/j.gastro.2017.05.011] [PMID: 28512021]
[155]
Bar-Sagi D, Hall A. Ras and Rho GTPases: a family reunion. Cell 2000; 103(2): 227-38.
[http://dx.doi.org/10.1016/S0092-8674(00)00115-X] [PMID: 11057896]
[156]
Leung KF, Baron R, Seabra MC. Thematic review series: lipid posttranslational modifications. Geranylgeranylation of rab GTPases. J Lipid Res 2006; 47(3): 467-75.
[http://dx.doi.org/10.1194/jlr.R500017-JLR200] [PMID: 16401880]
[157]
Rubins JB, Greatens T, Kratzke RA, Tan AT, Polunovsky VA, Bitterman P. Lovastatin induces apoptosis in malignant mesothelioma cells. Am J Respir Crit Care Med 1998; 157(5 Pt. 1): 1616-22.
[http://dx.doi.org/10.1164/ajrccm.157.5.9709020] [PMID: 9603146]
[158]
Wang Z, Wu Y, Wang H, et al. Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility. Proc Natl Acad Sci USA 2014; 111(1): E89-98.
[http://dx.doi.org/10.1073/pnas.1319190110] [PMID: 24367099]
[159]
Lebowitz PF, Casey PJ, Prendergast GC, Thissen JA. Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. J Biol Chem 1997; 272(25): 15591-4.
[http://dx.doi.org/10.1074/jbc.272.25.15591] [PMID: 9188444]
[160]
Wang M, Casey PJ. Protein prenylation: unique fats make their mark on biology. Nat Rev Mol Cell Biol 2016; 17(2): 110-22.
[http://dx.doi.org/10.1038/nrm.2015.11] [PMID: 26790532]
[161]
Xia Z, Tan MM, Wong WW, Dimitroulakos J, Minden MD, Penn LZ. Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells. Leukemia 2001; 15(9): 1398-407.
[http://dx.doi.org/10.1038/sj.leu.2402196] [PMID: 11516100]
[162]
Agarwal B, Bhendwal S, Halmos B, Moss SF, Ramey WG, Holt PR. Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res 1999; 5(8): 2223-9.
[PMID: 10473109]
[163]
Ghosh PM, Ghosh-Choudhury N, Moyer ML, et al. Role of RhoA activation in the growth and morphology of a murine prostate tumor cell line. Oncogene 1999; 18(28): 4120-30.
[http://dx.doi.org/10.1038/sj.onc.1202792] [PMID: 10435593]
[164]
Hodis E, Watson IR, Kryukov GV, et al. A landscape of driver mutations in melanoma. Cell 2012; 150(2): 251-63.
[http://dx.doi.org/10.1016/j.cell.2012.06.024] [PMID: 22817889]
[165]
Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res 2012; 18(4): 1167-76.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-2109] [PMID: 22228640]
[166]
Held MA, Langdon CG, Platt JT, et al. Genotype-selective combination therapies for melanoma identified by high-throughput drug screening. Cancer Discov 2013; 3(1): 52-67.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0408] [PMID: 23239741]
[167]
Chang M-Y, Jan MS, Won SJ, Liu HS. Ha-rasVal12 oncogene increases susceptibility of NIH/3T3 cells to lovastatin. Biochem Biophys Res Commun 1998; 248(1): 62-8.
[http://dx.doi.org/10.1006/bbrc.1998.8911] [PMID: 9675086]
[168]
Hansen CG, Moroishi T, Guan K-L. YAP and TAZ: a nexus for hippo signaling and beyond. Trends Cell Biol 2015; 25(9): 499-513.
[http://dx.doi.org/10.1016/j.tcb.2015.05.002] [PMID: 26045258]
[169]
Harvey KF, Zhang X, Thomas DM. The hippo pathway and human cancer. Nat Rev Cancer 2013; 13(4): 246-57.
[http://dx.doi.org/10.1038/nrc3458] [PMID: 23467301]
[170]
Cordenonsi M, Zanconato F, Azzolin L, et al. The hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 2011; 147(4): 759-72.
[http://dx.doi.org/10.1016/j.cell.2011.09.048] [PMID: 22078877]
[171]
Sorrentino G, Ruggeri N, Specchia V, et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol 2014; 16(4): 357-66.
[http://dx.doi.org/10.1038/ncb2936] [PMID: 24658687]
[172]
Hao F, Q Zu, J Wang, et al. Statins potently inhibit YAP function and proliferation of pancreatic ductal adenocarcinoma cancer (PDAC) cells. Gastroenterology 2017; 152(5): S837-8.
[http://dx.doi.org/10.1016/S0016-5085(17)32892-5]
[173]
Iannelli F, Maria SR, Chiara C, et al. Abstract 2877: synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting cancer stem cells compartment via YAP-pathway modulation. Cancer Res 2018; 78(13)(Suppl.): 2877-7.
[174]
Kuzu OF, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res 2016; 76(8): 2063-70.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2613] [PMID: 27197250]
[175]
Silvius JR. Role of cholesterol in lipid raft formation: lessons from lipid model systems. Biochim Biophys Acta 2003; 1610(2): 174-83.
[http://dx.doi.org/10.1016/S0005-2736(03)00016-6] [PMID: 12648772]
[176]
Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest 2002; 110(5): 597-603.
[http://dx.doi.org/10.1172/JCI0216390] [PMID: 12208858]
[177]
Llaverias G, Danilo C, Mercier I, et al. Role of cholesterol in the development and progression of breast cancer. Am J Pathol 2011; 178(1): 402-12.
[http://dx.doi.org/10.1016/j.ajpath.2010.11.005] [PMID: 21224077]
[178]
Alikhani N, Ferguson RD, Novosyadlyy R, et al. Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic mouse model. Oncogene 2013; 32(8): 961-7.
[http://dx.doi.org/10.1038/onc.2012.113] [PMID: 22469977]
[179]
Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol 2002; 168(1): 9-12.
[http://dx.doi.org/10.1016/S0022-5347(05)64820-3] [PMID: 12050481]
[180]
Sonnenschein C, Soto AM. An updated review of environmental estrogen and androgen mimics and antagonists. J Steroid Biochem Mol Biol 1998; 65(1-6): 143-50.
[http://dx.doi.org/10.1016/S0960-0760(98)00027-2] [PMID: 9699867]
[181]
Chlebowski RT, Hendrix SL, Langer RD, et al. WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 2003; 289(24): 3243-53.
[http://dx.doi.org/10.1001/jama.289.24.3243] [PMID: 12824205]
[182]
DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP. 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol Endocrinol 2008; 22(1): 65-77.
[http://dx.doi.org/10.1210/me.2007-0383] [PMID: 17872378]
[183]
Nelson ER, Wardell SE, Jasper JS, et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science 2013; 342(6162): 1094-8.
[http://dx.doi.org/10.1126/science.1241908] [PMID: 24288332]
[184]
Boyd NF, McGuire V. Evidence of association between plasma high-density lipoprotein cholesterol and risk factors for breast cancer. J Natl Cancer Inst 1990; 82(6): 460-8.
[http://dx.doi.org/10.1093/jnci/82.6.460] [PMID: 2313717]
[185]
Ferraroni M, Gerber M, Decarli A, et al. HDL-cholesterol and breast cancer: a joint study in northern italy and southern France. Int J Epidemiol 1993; 22(5): 772-80.
[http://dx.doi.org/10.1093/ije/22.5.772] [PMID: 8282454]
[186]
Kitahara CM, Berrington de González A, Freedman ND, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol 2011; 29(12): 1592-8.
[http://dx.doi.org/10.1200/JCO.2010.31.5200] [PMID: 21422422]
[187]
Sun L-P, Seemann J, Goldstein JL, Brown MS. Sterol-regulated transport of SREBPs from endoplasmic reticulum to golgi: insig renders sorting signal in scap inaccessible to COPII proteins. Proc Natl Acad Sci USA 2007; 104(16): 6519-26.
[http://dx.doi.org/10.1073/pnas.0700907104] [PMID: 17428919]
[188]
Yang T, Espenshade PJ, Wright ME, et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 2002; 110(4): 489-500.
[http://dx.doi.org/10.1016/S0092-8674(02)00872-3] [PMID: 12202038]
[189]
Sato R. Sterol metabolism and SREBP activation. Arch Biochem Biophys 2010; 501(2): 177-81.
[http://dx.doi.org/10.1016/j.abb.2010.06.004] [PMID: 20541520]
[190]
Trapani L, Segatto M, Pallottini V. Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic “power station”. World J Hepatol 2012; 4(6): 184-90.
[http://dx.doi.org/10.4254/wjh.v4.i6.184] [PMID: 22761969]
[191]
Xiao X, Song B-L. SREBP: a novel therapeutic target. Acta Biochim Biophys Sin (Shanghai) 2013; 45(1): 2-10.
[http://dx.doi.org/10.1093/abbs/gms112] [PMID: 23257291]
[192]
Matsuda M, Korn BS, Hammer RE, et al. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev 2001; 15(10): 1206-16.
[http://dx.doi.org/10.1101/gad.891301] [PMID: 11358865]
[193]
Meier-Stephenson V, Riemer J, Narendran A. The HIV protease inhibitor, nelfinavir, as a novel therapeutic approach for the treatment of refractory pediatric leukemia. OncoTargets Ther 2017; 10: 2581-93.
[http://dx.doi.org/10.2147/OTT.S136484] [PMID: 28553123]
[194]
Jiang W, Mikochik PJ, Ra JH, et al. HIV protease inhibitor nelfinavir inhibits growth of human melanoma cells by induction of cell cycle arrest. Cancer Res 2007; 67(3): 1221-7.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3377] [PMID: 17283158]
[195]
Smith MP, Brunton H, Rowling EJ, et al. Inhibiting drivers of non-mutational drug tolerance is a salvage strategy for targeted melanoma therapy. Cancer Cell 2016; 29(3): 270-84.
[http://dx.doi.org/10.1016/j.ccell.2016.02.003] [PMID: 26977879]
[196]
Echeverría F, Valenzuela R, Espinosa A, et al. Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: involvement of resolvins RvE1/2 and RvD1/2. J Nutr Biochem 2019; 63: 35-43.
[http://dx.doi.org/10.1016/j.jnutbio.2018.09.012] [PMID: 30321750]
[197]
Xu HF, Luo J, Wang HP, et al. Sterol regulatory element binding protein-1 (SREBP-1)c promoter: characterization and transcriptional regulation by mature SREBP-1 and liver X receptor α in goat mammary epithelial cells. J Dairy Sci 2016; 99(2): 1595-604.
[http://dx.doi.org/10.3168/jds.2015-10353] [PMID: 26709176]
[198]
Knight BL, Hebbachi A, Hauton D, et al. A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver. Biochem J 2005; 389(Pt. 2): 413-21.
[http://dx.doi.org/10.1042/BJ20041896] [PMID: 15777286]
[199]
Pettinelli P, Del Pozo T, Araya J, et al. Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim Biophys Acta 2009; 1792(11): 1080-6.
[http://dx.doi.org/10.1016/j.bbadis.2009.08.015] [PMID: 19733654]
[200]
Echeverría F, Valenzuela R, Bustamante A, et al. High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration. Food Funct 2019; 10(9): 6170-83.
[http://dx.doi.org/10.1039/C9FO01373C] [PMID: 31501836]
[201]
Berger J, Moller DE. and. The mechanisms of action of PPARs Annu Rev Med 2002; 53(1): 409-35.
[http://dx.doi.org/10.1146/annurev.med.53.082901.104018] [PMID: 11818483]
[202]
Clark RB. The role of PPARs in inflammation and immunity. J Leukoc Biol 2002; 71(3): 388-400.
[PMID: 11867676]
[203]
Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996; 37(5): 907-25.
[PMID: 8725145]
[204]
Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol 2006; 97(8A)(Suppl. 1): 52C-60C.
[http://dx.doi.org/10.1016/j.amjcard.2005.12.010] [PMID: 16581329]
[205]
He Q-F, Xu Y, Li J, Huang ZM, Li XH, Wang X. CD8+ T-cell exhaustion in cancer: mechanisms and new area for cancer immunotherapy. Brief Funct Genomics 2019; 18(2): 99-106.
[http://dx.doi.org/10.1093/bfgp/ely006] [PMID: 29554204]
[206]
Ma X, Bi E, Huang C, et al. Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity. J Exp Med 2018; 215(6): 1555-69.
[http://dx.doi.org/10.1084/jem.20171576] [PMID: 29743292]
[207]
Ma X, Bi E, Lu Y, et al. Cholesterol induces CD8+ T cell exhaustion in the tumor microenvironment Cell Metab 2019; 30(1): 143-156. e5.
[http://dx.doi.org/10.1016/j.cmet.2019.04.002] [PMID: 31031094]

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