Next-generation KRAS G12C inhibitor olomorasib shows promising pan-tumor activity in a first-in-human study. ORR ~37% in non-CRC tumors with durable response. Activity even observed after prior KRAS G12C inhibitors. KRAS targeting keeps evolving. nature.com/articles/s41467-0…

Primary vs Metastasis: Genomic Differences In the analysis of 5,692 matched primary–metastatic samples from 2,846 patients in the AACR Project GENIE database: 🔹️Metastatic tumors show a modest increase in mutation burden 🔹️FGA is higher → reflecting metastatic genomic instability 🔹️Eleven genes are more frequent in metastases (MYC, CDKN2A, ESR1, AR, etc.) 🔹️The most pronounced differences appear in lung, breast, colorectal, pancreatic, and prostate cancers. 💬The study shows that metastatic tumors exhibit a limited but biologically interpretable degree of genomic divergence compared with primary tumors (likely under therapeutic selection), with the major separation arising from copy-number alterations and structural variants. The clinical utility of re-biopsy therefore varies by tumor type and by the expected dynamics of metastatic evolution. tandfonline.com/doi/full/10.…