Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Undruggable proteins are a class of proteins that are often characterized by large, complex
structures or functions that are difficult to interfere with using conventional drug design …
structures or functions that are difficult to interfere with using conventional drug design …
Small molecule inhibitors targeting the cancers
Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and
tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer …
tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer …
Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS
CJ Schulze, KJ Seamon, Y Zhao, YC Yang, J Cregg… - Science, 2023 - science.org
The discovery of small-molecule inhibitors requires suitable binding pockets on protein
surfaces. Proteins that lack this feature are considered undruggable and require innovative …
surfaces. Proteins that lack this feature are considered undruggable and require innovative …
Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC
MV Negrao, HA Araujo, G Lamberti, AJ Cooper… - Cancer discovery, 2023 - AACR
Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRAS G12C-
mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 …
mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 …
JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors
E Lorthiois, M Gerspacher, KS Beyer… - Journal of medicinal …, 2022 - ACS Publications
Rapid emergence of tumor resistance via RAS pathway reactivation has been reported from
clinical studies of covalent KRASG12C inhibitors. Thus, inhibitors with broad potential for …
clinical studies of covalent KRASG12C inhibitors. Thus, inhibitors with broad potential for …
Kras oncogene ablation prevents resistance in advanced lung adenocarcinomas
M Salmón, R Álvarez-Díaz… - The Journal of …, 2023 - Am Soc Clin Investig
KRASG12C inhibitors have revolutionized the clinical management of patients with KRAS
G12C-mutant lung adenocarcinoma. However, patient exposure to these inhibitors leads to …
G12C-mutant lung adenocarcinoma. However, patient exposure to these inhibitors leads to …
Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy
Non–small lung cancers (NSCLC) frequently (∼ 30%) harbor KRAS driver mutations, half of
which are KRAS G12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is …
which are KRAS G12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is …
Clinical and Genomic Features of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients With Advanced KRAS G12C-Mutant Non–Small Cell Lung …
PURPOSE With the recent approval of the KRAS G12C inhibitor sotorasib for patients with
advanced KRAS G12C-mutant non–small cell lung cancer (NSCLC), there is a new need to …
advanced KRAS G12C-mutant non–small cell lung cancer (NSCLC), there is a new need to …
Resistance to KRAS G12C inhibition in non-small cell lung cancer
A Di Federico, I Ricciotti, V Favorito… - Current Oncology …, 2023 - Springer
Abstract Purpose of Review Although the recent development of direct KRASG12C inhibitors
(G12Ci) has improved outcomes in KRAS mutant cancers, responses occur only in a fraction …
(G12Ci) has improved outcomes in KRAS mutant cancers, responses occur only in a fraction …
[HTML][HTML] Precision oncology provides opportunities for targeting KRAS-inhibitor resistance
Novel inhibitors targeting Kirsten rat sarcoma virus homolog (KRAS) KRAS G12C in various
cancers have shown good initial efficacy, but therapy-related drug resistance eventually …
cancers have shown good initial efficacy, but therapy-related drug resistance eventually …