RAS/RAF co-mutation and ERBB2 copy number modulates HER2 heterogeneity and responsiveness to HER2-directed therapy in colorectal cancer.
Harshabad SinghPranshu SahgalKevin S KapnerSteven M CorselloHersh V GuptaRahul GujrathiYvonne Y LiAndrew D CherniakRaquelle El AlamJoseph A KerfootElizabeth AndrewsAnnette LeeChetan NambiarAlison M HanniganJoshua RemlandLauren K BraisMeghan E LeahyDouglas A RubinsonBenjamin L SchlechterMatthew L MeyersonYanan KuangCloud P PaweletzJessica K LeeJulia Coelho França QuintanilhaAndrew J AguirreKimberley J PerezBrandon M HuffmanHumberto RossiThomas A AbramsSheheryar K KabrajiLivio TrusolinoAndrea BertottiEwa T SicinskaAparna Raj ParikhBrian M WolpinAlexa B SchrockMarios GiannakisKimmie NgJeffrey A MeyerhardtJason L HornickNilay S SethiJames M ClearyPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2024)
Co-occurring RAS/RAF alterations define a unique subtype of ERBB2 amplified CRC that has increased intratumoral heterogeneity, interlesional discordance and resistance to trastuzumab-based combinations. Further examination of trastuzumab deruxtecan in this previously understudied cohort of ERBB2 amplified CRC is warranted.