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    almost2years
    Biomarkers of acquired resistance to sotorasib (soto) plus panitumumab (pani) in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) (AACR 2023)
    "Of 21 pts with paired plasma samples, 17 (81%) had ≥1 acquired genomic alteration. RTK alterations and secondary (2°) RAS alterations were most common; each occurred in 57% of pts (Table). KRAS amplification was the most common single alteration (43%)."
    Preclinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR amplification • RAS mutation • NRAS Q61K • HER-2 S310F • KRAS G12 • NRAS Q61 • NRAS Q61R • KRAS Q61H • KRAS amplification • NRAS Q61L • EGFR G465R • EGFR S464L • KRAS Q61L
    |
    Guardant360® CDx
    |
    Vectibix (panitumumab) • Lumakras (sotorasib)
    over2years
    Structure-guided and phage-assisted evolution of a therapeutic anti-EGFR antibody to reverse acquired resistance. (PubMed, Nat Commun)
    The evolved cetuximab variants (Ctx-VY, Ctx-Y104D and Ctx-W52D) with one or two amino acid substitutions in the complementarity-determining region inherit the optimized physical and chemical properties of cetuximab to a great extent, thus ensuring their druggability. Our data collectively show that structure-guided and phage-assisted evolution is an efficient and general approach for reversing receptor mutation-mediated resistance to therapeutic antibody drugs.
    Preclinical • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR S492R • EGFR G465R
    |
    Erbitux (cetuximab)