Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma

被引：166

作者：

Girotti, Maria Romina ^{[1
]}

Gremel, Gabriela ^{[1
]}

Lee, Rebecca ^{[1
]}

Galvani, Elena ^{[1
]}

Rothwell, Dominic ^{[2
]}

Viros, Amaya ^{[1
]}

Mandal, Amit Kumar ^{[1
]}

Lim, Kok Haw Jonathan ^{[1
]}

Saturno, Grazia ^{[1
]}

Furney, Simon J. ^{[1
]}

Baenke, Franziska ^{[1
]}

Pedersen, Malin ^{[3
]}

Rogan, Jane ^{[4
]}

Swan, Jacqueline ^{[5
]}

Smith, Matthew ^{[1
]}

Fusi, Alberto ^{[4
]}

Oudit, Deemesh ^{[4
]}

Dhomen, Nathalie ^{[1
]}

Brady, Ged ^{[2
]}

Lorigan, Paul ^{[4
]}

Dive, Caroline ^{[2
]}

Marais, Richard ^{[1
]}

机构：

[1] Canc Res UK Manchester Inst, Mol Oncol Grp, Manchester, Lancs, England

[2] Canc Res UK Manchester Inst, Clin & Expt Pharmacol Grp, Manchester, Lancs, England

[3] Inst Canc Res, Targeted Therapy Team, London SW3 6JB, England

[4] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England

[5] Canc Res UK Manchester Inst, Res Serv, Manchester, Lancs, England

来源：

CANCER DISCOVERY | 2016年 / 6卷 / 03期

基金：

英国惠康基金;

关键词：

CIRCULATING TUMOR DNA; KINASE-DEAD BRAF; ACQUIRED-RESISTANCE; MEK INHIBITION; CLINICAL-RESPONSE; DRUG-SENSITIVITY; CANCER; PLASMA; VEMURAFENIB; DISEASE;

D O I：

10.1158/2159-8290.CD-15-1336

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from similar to 9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell-derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma. SIGNIFICANCE: Although recent developments have revolutionized melanoma care, most patients still die of their disease. To improve melanoma outcomes further, we developed a powerful precision medicine platform to monitor patient responses and to identify and validate hypothesis-driven therapies for patients who do not respond, or who develop resistance to current treatments. (C) 2015 AACR.

引用

页码：286 / 299

页数：14

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