KRAS mutation: from undruggable to druggable in cancer

L Huang, Z Guo, F Wang, L Fu - Signal transduction and targeted …, 2021 - nature.com
Cancer is the leading cause of death worldwide, and its treatment and outcomes have been
dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene …

The current state of the art and future trends in RAS-targeted cancer therapies

SR Punekar, V Velcheti, BG Neel… - Nature reviews Clinical …, 2022 - nature.com
Despite being the most frequently altered oncogenic protein in solid tumours, KRAS has
historically been considered 'undruggable'owing to a lack of pharmacologically targetable …

Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer

SB Kemp, N Cheng, N Markosyan, R Sor, IK Kim… - Cancer discovery, 2023 - AACR
Mutations in the KRAS oncogene are found in more than 90% of patients with pancreatic
ductal adenocarcinoma (PDAC), with Gly-to-Asp mutations (KRAS G12D) being the most …

Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants

MH Hofmann, D Gerlach, S Misale, M Petronczki… - Cancer Discovery, 2022 - AACR
KRAS is the most frequently mutated oncogene, harboring mutations in approximately one
in seven cancers. Allele-specific KRASG12C inhibitors are currently changing the treatment …

Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in …

Q Zhou, M Chen, O Jiang, Y Pan, D Hu, Q Lin… - The Lancet …, 2022 - thelancet.com
Background A substantial proportion of patients with unresectable stage III non-small-cell
lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so …

Drugging KRAS: current perspectives and state-of-art review

K Parikh, G Banna, SV Liu, A Friedlaender… - Journal of hematology & …, 2022 - Springer
After decades of efforts, we have recently made progress into targeting KRAS mutations in
several malignancies. Known as the 'holy grail'of targeted cancer therapies, KRAS is the …

The KRAS-G12C inhibitor: activity and resistance

J Liu, R Kang, D Tang - Cancer gene therapy, 2022 - nature.com
Although it has long been deemed “undruggable”, with the development of drugs specifically
binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS …

The expanding role for small molecules in immuno-oncology

R Offringa, L Kötzner, B Huck, K Urbahns - Nature Reviews Drug …, 2022 - nature.com
The advent of immune checkpoint inhibition (ICI) using antibodies against PD1 and its
ligand PDL1 has prompted substantial efforts to develop complementary drugs. Although …

Adagrasib: first approval

S Dhillon - Drugs, 2023 - Springer
Adagrasib (KRAZATI™) is an orally available, potent, irreversible, small molecule inhibitor of
KRAS G12C mutant isoform being developed by Mirati Therapeutics for the treatment of …

Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance

V Thatikonda, H Lyu, S Jurado, K Kostyrko, CA Bristow… - Nature Cancer, 2024 - nature.com
Combination approaches are needed to strengthen and extend the clinical response to
KRASG12C inhibitors (KRASG12Ci). Here, we assessed the antitumor responses of …