Detection of Mutant RAS Subpopulations in Colorectal Cancer Patients

Abstract

Acquired resistance to molecularly targeted therapies is a major obstacle blocking effective treatment of cancer patients. This is particularly true for therapies that target the epidermal growth factor receptor (EGFR) [1], [2]. Acquired resistance to molecularly targeted therapies may occur de novo (meaning as a consequence of the selective pressure of treatment), or may be due to outgrowth of preexisting tumor subpopulations that are resistant to treatment [3]. Clinical studies have shown that undetected populations of tumor cells carrying KRAS mutations lead to therapeutic resistance and relapse in colorectal cancer (CRC) patients [4], [5]. Consequently, the ability to assess the impact of minor mutant subpopulations on therapeutic resistance has important implications regarding the development of effective strategies for personalized cancer treatment. Detecting and analyzing the major and minor mutant subpopulations of cells carrying specific oncogene mutations in a patient's tumor, therefore, are crucial.