AKT1 E17K is the most frequent gain of function mutation of the AKT1 gene. This mutation promotes pathologic localization of AKT1 to the plasma membrane and has been shown to induce leukemia in mice. Current options for AKT1 E17K-driven tumors are limited.
Wee1 and PKMYT1 are two kinases involved in DNA damage repair. The former is located in the nucleus and the latter in the endoplasmic reticulum. Several selective inhibitors of Wee1 or PKMYT1 have been tested in the clinical setting as monotherapy or in combination with other drugs.
Currently, cancer therapy trial-and-error methodology is inefficient and unsustainable. Oncology is the worst therapeutic area for drug trial success; only 3.4% of drugs that enter phase I end up being FDA approved, and 57% fail due to poor drug efficacy in trials. Building tools that may aid in predicting an individual’s response to a specific therapy may help in reducing costs, guesswork, and importantly improve the outcome of patients and accelerate new drug development.
FMS‐like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase validated as a therapeutic target for acute myeloid leukemia (AML) and regarded as an indicator of poor prognosis. Unfortunately, current FLT3 inhibitors, such as midostaurin, quizartinib or gilteritinib, often lead to myelosuppression or cardiovascular toxicity.
Researchers from Boehringer Ingelheim Pharma GmbH & Co. KG presented the discovery and preclinical characterization of BI-3706674, a potent and orally available small-molecule inhibitor of the KRAS oncogene, targeting both KRAS-mutant and KRAS wild-type amplified (WTamp) cancers.
Opna Bio AG recently provided findings from preclinical studies of novel dual E1A binding protein P300 (EP300) and CREB binding protein (CBP) inhibitors under investigation as potential anticancer agents.
Researchers from Loxo Oncology at Eli Lilly and Co. recently reported the discovery and preclinical evaluation of a new highly potent and selective pan-KRAS inhibitor, LY-4066434, being developed for the treatment of cancer.
Data regarding an innovative bispecific antibody – CPL-976 (CPBT-0976) – were recently reported by Celon Pharma SA. Bispecific antibodies targeting more than one antigen on cancer cells improve the specificity and effectiveness of the therapy, and could be utilized for targeting the defense mechanisms of cancer cells, such PD-L1 or EGFR, VEGFR and AXL.
The checkpoint kinase WEE1 catalyzes the inhibition of cell cycle progression and CDK1 phosphorylation. WEE1 inhibitors have demonstrated clinical benefits in gynecological malignancies, yet limited antitumor activity and a multifaceted toxicity profile of small-molecule inhibitors mean new approaches to target WEE1 are needed.
Researchers from Revolution Medicines Inc. presented the discovery and preclinical characterization of RMC-5127, a novel noncovalent, tri-complex inhibitor of GTPase KRAS (G12V mutant), or KRAS G12V(ON).
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