KRAS mutation: from undruggable to druggable in cancer
Nov 15, 2021 · Recently, there has been light on the horizon for one specific mutation, KRAS (G12C). With the discovery of a new allosteric site of KRAS (G12C), several irreversible covalently binding...
The KRAS-G12C inhibitor: activity and resistance - Nature
Sep 1, 2021 · 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 have recently...
FDA approves sotorasib with panitumumab for KRAS G12C …
On January 15, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C-mutated metastatic ...
Sotorasib is First KRAS Inhibitor Approved by FDA - NCI
Jun 25, 2021 · The discovery and approval of sotorasib “opens up opportunities for developing compounds that bind to other mutant [KRAS] proteins,” Dr. McCormick said. G12C is one of several KRAS mutations found in cancer cells. The two most common KRAS mutations are called G12D and G12V.
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
Sep 20, 2020 · We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was...
The path to the clinic: a comprehensive review on direct KRAS G12C ...
Jan 19, 2022 · Analyzing amino acid-specific KRAS mutations in the three cancer types responsible for most KRAS mutations, the most common KRAS mutation in NSCLC adenocarcinoma subtype is KRAS G12C (glycine to cysteine) (33.4%), while the most common KRAS mutation in colon and rectal adenocarcinoma and pancreatic ductal adenocarcinoma is …
Targeting KRAS in cancer - Nature Medicine
Apr 18, 2024 · The first successes occurred with allele-specific targeting of KRAS p.Gly12Cys (G12C) in non-small cell lung cancer, resulting in regulatory approval of two agents—sotorasib and adagrasib.
Sotorasib for Lung Cancers with KRAS p.G12C Mutation
Jun 4, 2021 · Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of...
Targeting KRAS G12C in Non-Small-Cell Lung Cancer: Current
Despite efforts to develop drugs aimed at inhibiting KRAS or its signaling pathways, KRAS had remained undruggable for decades. The discovery of a small pocket in the binding switch II region of KRAS G12C has revolutionized the treatment of KRAS G12C-mutated NSCLC patients.
Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of ...
Nov 12, 2020 · Recent advances in medicinal chemistry have established inhibitors targeting KRAS (G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers.
Acquired Resistance to KRAS G12C Inhibition in Cancer - The New …
Jun 23, 2021 · Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS G12C)....
KRAS G12C Mutations in NSCLC: From Target to Resistance
One such alteration in non-small cell lung cancer is the Kirsten Rat Sarcoma (KRAS) oncogene. KRAS mutations are the most common oncogenic driver in NSCLC, representing roughly 20–25% of cases. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time.
What’s new in KRAS mutation research? - MD Anderson Cancer Center
Apr 4, 2024 · There are also efforts to develop similarly selective drugs that target a mutation like KRAS G12D to better treat pancreatic cancer, or even one to target multiple different KRAS mutations, which would be called a pan-KRAS inhibitor.
The path to the clinic: a comprehensive review on direct KRAS G12C ...
Jan 19, 2022 · Adagrasib (MRTX849) and other direct KRAS G12C inhibitors are currently being investigated in multiple clinical trials. In this review, we delve into the path leading to the development of this novel KRAS inhibitor, starting with the discovery, structure, and function of the RAS family of oncoproteins.
SRC kinase drives multidrug resistance induced by KRAS-G12C
Dec 11, 2024 · Here, we show that MRTX849, a covalent inhibitor targeting the KRAS-G12C mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.
FDA APPROVES LUMAKRAS® (SOTORASIB) IN COMBINATION …
6 days ago · Approval is based on the pivotal Phase 3 CodeBreaK 300 study, which demonstrated that LUMAKRAS plus Vectibix is the first and only targeted treatment combination for chemorefractory KRAS G12C ...
Comprehensive pan-cancer genomic landscape of KRAS altered …
KRAS G12D (29%), G12V (23%), G12C (15%), G13D (7%), and G12R (5%) were the five most common KRAS mutant isoforms together accounting for ~80% of all KRAS alterations.
Distribution of KRAS G12C Somatic Mutations across Race, Sex, …
Jan 13, 2021 · We studied the distribution of KRASG12C mutations in 32,138 patients with cancer across race (Asian, Black, and White) and sex and in 10 cancer types (Table S1.1 in Supplementary Appendix 2). A...
Treatment for KRAS G12C-mutated metastatic CRC approved by …
Jan 17, 2025 · The KRAS G12C mutation is present in approximately 3-5% of colorectal cancers, emphasizing the important role of comprehensive biomarker testing in mCRC. By detecting an actionable mutation, eligible patients are now able to receive a corresponding targeted therapy that may lead to improved responses.
Lumakras Plus Vectibix Approved for KRAS G12C-Mutated …
2 days ago · The recommended dose of Lumakras for KRAS G12C-mutated mCRC is 960mg orally once daily in combination with panitumumab until disease progression or unacceptable toxicity. The first dose of ...
FDA Greenlights Amgen's New Cancer Drug Combo, Boosting …
6 days ago · The decision, announced Thursday, applies to adults whose tumors carry the KRAS G12C mutation. Amgen's treatment pairs Lumakras (sotorasib) with Vectibix (panitumumab), an epidermal growth factor ...
Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRAS G12C …
Jun 3, 2022 · Adagrasib, a KRAS G12C inhibitor, irreversibly and selectively binds KRAS G12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in...
FDA Approves Breakthrough for KRAS-Mutated Colorectal Cancer
5 days ago · THE U.S. Food and Drug Administration (FDA) approved a novel combination therapy for adults with KRAS G12C-mutated metastatic colorectal cancer (mCRC). This approval, based on results from the CodeBreaK 300 clinical trial, offers a new treatment option for patients who have progressed after prior chemotherapy regimens involving fluoropyrimidine ...
FDA Approval Alert: The Need-to-Know - cancernetwork.com
In January 2025, the FDA approved sotorasib plus panitumumab for patients with KRAS G12C-mutated metastatic colorectal cancer, determined by an FDA-approved test, and for those who have previously received therapy including fluoropyrimidine, oxaliplatin, or irinotecan.
Divarasib plus cetuximab in KRAS G12C -positive colorectal
Dec 5, 2023 · Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C -positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream...
FDA Approves LUMAKRAS With Vectibix For KRAS G12C-Mutated …
Jan 17, 2025 · The approval also underscores the significance of KRAS G12C as a biomarker, as the combination therapy represents the first and only targeted treatment for this mutation to show improved PFS in ...
Sotorasib in KRAS p.G12C–Mutated Advanced Pancreatic Cancer
Dec 21, 2022 · We conducted an international, multicenter, open-label, phase 1–2 trial to evaluate the efficacy and safety of sotorasib as monotherapy in patients with KRAS p.G12C–mutated pancreatic...
Amgen picks up key colorectal cancer okay for KRAS drug
5 days ago · KRAS mutations are among the most common genetic alterations in CRC, with the KRAS G12C mutation present in approximately 3% to 5% of cases. "Lumakras plus Vectibix offers a targeted, biomarker ...
Quantum-computing-enhanced algorithm unveils potential KRAS …
2 days ago · Nagasaka, M. et al. KRas G12C Game of Yhrones, which direct KRas inhibitor will claim the iron throne? Cancer Treat. Rev. 84, 101974 (2020).