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Cancer Cell DOI:10.1016/j.ccell.2018.03.025

A Convergence-Based Framework for Cancer Drug Resistance.

Publication TypeJournal Article
Year of Publication2018
AuthorsKonieczkowski, DJ, Johannessen, CM, Garraway, LA
JournalCancer Cell
Date Published2018 05 14
KeywordsBiomarkers, Tumor, Drug Resistance, Neoplasm, Humans, Immunotherapy, Molecular Targeted Therapy, Neoplasms, Precision Medicine

Despite advances in cancer biology and therapeutics, drug resistance remains problematic. Resistance is often multifactorial, heterogeneous, and prone to undersampling. Nonetheless, many individual mechanisms of targeted therapy resistance may coalesce into a smaller number of convergences, including pathway reactivation (downstream re-engagement of original effectors), pathway bypass (recruitment of a parallel pathway converging on the same downstream output), and pathway indifference (development of a cellular state independent of the initial therapeutic target). Similar convergences may also underpin immunotherapy resistance. Such parsimonious, convergence-based frameworks may help explain resistance across tumor types and therapeutic categories and may also suggest strategies to overcome it.


Alternate JournalCancer Cell
PubMed ID29763622
PubMed Central IDPMC5957297
Grant ListR01 CA219943 / CA / NCI NIH HHS / United States
U54 CA224068 / CA / NCI NIH HHS / United States