Perspective Rational Cancer Treatment Combinations: An Urgent Clinical Need

被引：123

作者：

Boshuizen, Julia ^{[1
]}

Peeper, Daniel S. ^{[1
]}

机构：

[1] Netherlands Canc Inst, Oncode Inst, Div Mol Oncol & Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

来源：

MOLECULAR CELL | 2020年 / 78卷 / 06期

关键词：

KRAS-MUTANT LUNG; ACQUIRED-RESISTANCE; MEK INHIBITION; BREAST-CANCER; TARGETED THERAPY; ANTITUMOR IMMUNITY; BRAF INHIBITION; INTRATUMOR HETEROGENEITY; SYNTHETIC LETHALITY; TUMOR HETEROGENEITY;

D O I：

10.1016/j.molcel.2020.05.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We are witnessing several revolutionary technological advances in cancer. These innovations have not only contributed to a growing understanding of the tumor and its microenvironment but also uncovered an increasing array of new therapeutic targets. For most advanced cancers, therapy resistance limits the benefit of single-agent therapies. Therefore, some 5,000 clinical trials are ongoing globally to probe the clinical benefit of new combination treatments. However, the possibilities to combine individual treatments dramatically outnumber the patients available to enroll in clinical trials. This comes at a potential cost of missed opportunities, clinical failure, avoidable toxicity, insufficient patient accrual, and financial loss. A solution may be to design combination therapies more rationally, which are informed by fundamental biological and mechanistic insight. We will discuss some successes and failures of current treatment combinations, as well as interesting emerging preclinical concepts that warrant clinical exploration.

引用

页码：1002 / 1018

页数：17

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