Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/34985916/
Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the...
Relevance: There is an expanding list of approved targeted therapies including for BRAF V600E, EGFR exon 20 insertion, and KRAS G12C mutations, MET exon 14 alterations, and NTRK and RET rearrangements. In addition, there are numerous other oncogenic drivers, such as HER2 exon 20 insertion mutations, for which there are emerging efficacy data...
Rapid idiosyncratic mechanisms of clinical resistance to KRAS G12C inhibition - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/34990404/
The KRAS proto-oncogene is among the most frequently mutated genes in cancer, yet for 40 years it remained an elusive therapeutic target. Recently, allosteric inhibitors that covalently bind to KRAS...
Conclusion/Relevance: Together, our findings reveal numerous mechanisms of resistance to current KRAS G12C inhibitors through enrichment of clonal populations, KRAS-independent downstream signaling and diverse remodeling of the tumor microenvironment.
Targeting KRAS mutant lung cancer: light at the end of the tunnel - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/34951114/
For decades, KRAS mutant lung adenocarcinomas (LUAD) have been refractory to therapeutic strategies based on personalized medicine owing to the complexity of designing inhibitors to selectively target KRAS and downstream...
Conclusion/Relevance: Here, we discuss the mechanisms responsible for the rapid development of resistance to these inhibitors, as well as potential strategies to overcome this limitation. Other therapeutic strategies aimed at inhibiting KRAS oncogenic signaling by targeting either upstream activators or downstream effectors are also reviewed....
Integrative molecular analysis of combined small-cell lung carcinomas identifies major subtypes with different therapeutic opportunities - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/34952268/
1 Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy. 2 Pathology Unit 1, Pathology and Laboratory Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano,...
Conclusions: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).
Novel Small Molecules Capable of Blocking mtRAS-Signaling Pathway - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/34956887/
RAS mutants are involved in approximately 30% of all human cancers and have been regarded as undruggable targets owing to relatively smooth protein surface and obscure binding pockets. In our...
Conclusion/Relevance: Both SIJ1795 and SIJ1772 attenuate phosphorylation of RAS downstream molecules (AKT and MEK) and induce apoptosis and G0/G1 cell cycle arrest on cancer cells with mtRAS. Moreover, both substances substantially suppress the migration, invasion, and colony formation of cancer cells harboring mtRAS. Taken together, this study...