AUTHOR=Epstein Richard J. TITLE=The Unpluggable in Pursuit of the Undruggable: Tackling the Dark Matter of the Cancer Therapeutics Universe JOURNAL=Frontiers in Oncology VOLUME=3 YEAR=2013 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2013.00304 DOI=10.3389/fonc.2013.00304 ISSN=2234-943X ABSTRACT=
The notion that targeted drugs can unplug gain-of-function tumor pathways has revitalized pharmaceutical research, but the survival benefits of this strategy have so far proven modest. A weakness of oncogene-blocking approaches is that they do not address the problem of cancer progression as selected by the recessive phenotypes of genetic instability and apoptotic resistance which in turn arise from loss-of-function – i.e., undruggable – defects of caretaker (e.g.,