Understanding Drug Sensitivity and Tackling Resistance in Cancer
Jeffrey W. Tyner, Franziska Haderk, Anbarasu Kumaraswamy, Linda B. Baughn, Brian Van Ness, Song Liu, Himangi Marathe, Joshi J. Alumkal, Trever G. Bivona, Keith Syson Chan, Brian J. Druker, Alan D. Hutson, Peter S. Nelson, Charles L. Sawyers, Christopher D. Willey
Abstract
Decades of research into the molecular mechanisms of cancer and the development of novel therapeutics have yielded a number of remarkable successes. However, our ability to broadly assign effective, rationally targeted therapies in a personalized manner remains elusive for many patients, and drug resistance persists as a major problem. This is in part due to the well-documented heterogeneity of cancer, including the diversity of tumor cell lineages and cell states, the spectrum of somatic mutations, the complexity of microenvironments, and immune-suppressive features and immune repertoires, which collectively require numerous different therapeutic approaches. Here, we describe a framework to understand the types and biological causes of resistance, providing translational opportunities to tackle drug resistance by rational therapeutic strategies.