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The Journal of Clinical Investigation (JCI)
Targeted therapy gene mutations may: (a) encode a protein that can be targeted in a manner distinct from the WT protein; (b) cause abnormal activation of a protein that is druggable but for which mutant-specific targeting has not been achieved; or (c) create novel molecular dependencies that are druggable. This article describe key examples of genetic drivers and associated modes of druggability, considers the clinical and research challenges in the field, and discusses new approaches to maximizing therapeutic benefit of targeted therapies.
Oncology, Medical May 18th 2022
Northwestern Medicine
Blocking expression of FOXK2 in cancer stem cells inhibited growth of these cells, reducing their so-called “stemness,” making them more like normal cells.
Obstetrics & Gynecology May 11th 2022
Journal of Clinical Oncology
Adagrasib 600 mg twice a day was well tolerated and exhibited antitumor activity in patients with advanced solid tumors harboring the KRASG12C mutation.
Oncology, Medical May 4th 2022
OBR Oncology
The NR2F1 gene normally prevents pre-malignant cells from spreading to other parts of the body. HER2 suppresses NR2F1, allowing pre-cancerous cells to move to other organs where they can become cancerous.
JAMA Network
In this case-control registry study of 63,828 patients with 14 common cancer types and 37,086 controls, pathogenic variants in BRCA1 were associated with biliary tract cancer, BRCA2 was associated with esophageal cancer, and combined BRCA1/2, with gastric cancer.
Oncology, Medical April 19th 2022
PIK3CA is the most mutated oncogene across many of the common solid tumor types. Consequently, targeting PIK3CA has been of major clinical interest. Initial efforts at have not been promising, however. The limiting factors have primarily been lack of isoform specificity of inhibitors and dose-limiting toxicities. This study evaluates copanlisib, an α and δ isoform–specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations.
Oncology, Medical February 15th 2022