Scott Kopetz, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, talks through adaptive and acquired resistance to mitogen-activated protein kinase (MAPK)-targeted treatments in BRAF- and KRAS-mutated colorectal cancer. The Phase I/II KRYSTAL-1 trial (NCT03785249) utilized cetuximab alongside adagrasib, a MAPK inhibitor, to prevent reactivation of the MAPK pathway by EGFR signaling. Further improvement of MAPK-targeted therapies may come from identifying other receptor tyrosine kinases engaged in adaptive feedback, other forms of mutation or amplification, and better understanding the mechanisms of acquired resistance. This interview took place at American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, CA.
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