From the NIH: Overcoming Resistance to Targeted Anticancer Drugs

N Engl J Med. 2013 Nov 1. [Epub ahead of print]

Overcoming Resistance to Targeted Anticancer Drugs.

Doroshow JH.

Source

From the Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Abstract

More than a decade ago, imatinib, an agent that has a specific inhibitory interaction with the BCR-ABL fusion protein, was introduced for the treatment of chronic myeloid leukemia (CML). The introduction of this agent dramatically changed researchers' understanding not only of the role of tyrosine kinases as targets for oncology drugs (despite the conserved status of protein kinase domains in nature), but also their ability to conceptualize and test novel molecular mechanisms of action and drug resistance in solid tumors such as adenocarcinoma of the lung as well as in hematopoietic cancers.¹,² The underlying genetic instability of most cancers . . .