CCR 20th Anniversary Commentary: MAPK/ERK Pathway Inhibition in Melanoma-Kinase Inhibition Redux

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2015 Dec 17

PMID 26672083

Citations 1

Authors

Diwakar Davar

John M Kirkwood

Affiliations

Soon will be listed here.

Abstract

In the January 15, 2012, issue of Clinical Cancer Research, Kirkwood and colleagues published a study comparing the MEK inhibitor selumetinib with temozolomide in unselected metastatic melanoma. Although selumetinib did not improve survival or response, most responders had BRAF-activating mutations, and selumetinib has since demonstrated efficacy in BRAF-mutant melanoma. This study laid the groundwork for the evaluation of BRAF/MEK inhibitors in BRAF-mutant melanoma.

Citing Articles

Selumetinib Activity in Thyroid Cancer Cells: Modulation of Sodium Iodide Symporter and Associated miRNAs.

Wachter S, Wunderlich A, Greene B, Roth S, Elxnat M, Fellinger S Int J Mol Sci. 2018; 19(7).

PMID: 30018229 PMC: 6073679. DOI: 10.3390/ijms19072077.

References

Curtin J, Fridlyand J, Kageshita T, Patel H, Busam K, Kutzner H . Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353(20):2135-47. DOI: 10.1056/NEJMoa050092. View

Leach D, Krummel M, Allison J . Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996; 271(5256):1734-6. DOI: 10.1126/science.271.5256.1734. View

Haass N, Sproesser K, Nguyen T, Contractor R, Medina C, Nathanson K . The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin Cancer Res. 2008; 14(1):230-9. DOI: 10.1158/1078-0432.CCR-07-1440. View

Hainsworth J, Cebotaru C, Kanarev V, Ciuleanu T, Damyanov D, Stella P . A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. J Thorac Oncol. 2010; 5(10):1630-6. DOI: 10.1097/JTO.0b013e3181e8b3a3. View

Bennouna J, Lang I, Valladares-Ayerbes M, Boer K, Adenis A, Escudero P . A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens. Invest New Drugs. 2010; 29(5):1021-8. DOI: 10.1007/s10637-010-9392-8. View

Kirkwood J, Bastholt L, Robert C, Sosman J, Larkin J, Hersey P . Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin Cancer Res. 2011; 18(2):555-67. PMC: 3549298. DOI: 10.1158/1078-0432.CCR-11-1491. View

Flaherty K, Robert C, Hersey P, Nathan P, Garbe C, Milhem M . Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012; 367(2):107-14. DOI: 10.1056/NEJMoa1203421. View

Infante J, Fecher L, Falchook G, Nallapareddy S, Gordon M, Becerra C . Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol. 2012; 13(8):773-81. DOI: 10.1016/S1470-2045(12)70270-X. View

Daud A, Bastian B . Beyond BRAF in melanoma. Curr Top Microbiol Immunol. 2011; 355:99-117. DOI: 10.1007/82_2011_163. View

10.

Robert C, Dummer R, Gutzmer R, Lorigan P, Kim K, Nyakas M . 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. DOI: 10.1016/S1470-2045(13)70237-7. View

11.

Gupta A, Love S, Schuh A, Shanyinde M, Larkin J, Plummer R . DOC-MEK: a double-blind randomized phase II trial of docetaxel with or without selumetinib in wild-type BRAF advanced melanoma. Ann Oncol. 2014; 25(5):968-74. DOI: 10.1093/annonc/mdu054. View

12.

Carvajal R, Sosman J, Quevedo J, Milhem M, Joshua A, Kudchadkar R . Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014; 311(23):2397-405. PMC: 4249701. DOI: 10.1001/jama.2014.6096. View

13.

Perna D, Karreth F, Rust A, Perez-Mancera P, Rashid M, Iorio F . BRAF inhibitor resistance mediated by the AKT pathway in an oncogenic BRAF mouse melanoma model. Proc Natl Acad Sci U S A. 2015; 112(6):E536-45. PMC: 4330752. DOI: 10.1073/pnas.1418163112. View

14.

Yu X, Ambrosini G, Roszik J, Eterovic A, Stempke-Hale K, Seftor E . Genetic analysis of the 'uveal melanoma' C918 cell line reveals atypical BRAF and common KRAS mutations and single tandem repeat profile identical to the cutaneous melanoma C8161 cell line. Pigment Cell Melanoma Res. 2014; 28(3):357-9. DOI: 10.1111/pcmr.12345. View

15.

Johnson D, Sosman J . Therapeutic Advances and Treatment Options in Metastatic Melanoma. JAMA Oncol. 2015; 1(3):380-6. DOI: 10.1001/jamaoncol.2015.0565. View

16.

Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N . Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002; 99(19):12293-7. PMC: 129438. DOI: 10.1073/pnas.192461099. View

17.

Davies H, Bignell G, Cox C, Stephens P, Edkins S, Clegg S . Mutations of the BRAF gene in human cancer. Nature. 2002; 417(6892):949-54. DOI: 10.1038/nature00766. View

18.

Eisen T, Ahmad T, Flaherty K, Gore M, Kaye S, Marais R . Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer. 2006; 95(5):581-6. PMC: 2360687. DOI: 10.1038/sj.bjc.6603291. View

19.

Wilhelm S, Carter C, Tang L, Wilkie D, McNabola A, Rong H . BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004; 64(19):7099-109. DOI: 10.1158/0008-5472.CAN-04-1443. View