The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway comprises four JAK kinases and seven STAT transcription factors. Among the latter, STAT3 is the best-known oncogene and its essential role in normal tissue makes its complete blockage useless for treatment due to severe side effects.
Macrophages are specialized immune cells that can either stimulate or inhibit inflammation. Studies in mice suggest that phosphoinositide 3-kinase γ (PI3Kγ), a key mediator in macrophage signaling pathways predominantly expressed in myeloid cells, may promote immune suppression both in inflammation and in the tumor microenvironment.
Prostaglandin E2 (PGE2) regulates inflammation and the tumor microenvironment, thought to happen through engagement with the E-type prostanoid EP2 and EP4 receptors, exerting immunosuppression in the tumor microenvironment. The simultaneous blockade of EP2 and EP4 – not blocking either alone – is needed to overcome this immunosuppressor effect.
Researchers from Fochon Biosciences Ltd. have reported the discovery and preclinical evaluation of a novel second-generation B-cell lymphoma 2 (BCL2) inhibitor, FCN-683, being developed for the treatment of B-cell malignancies. FCN-683 showed the ability to potently and selectively inhibit both wild-type BCL2 (IC50=0.11 nM) and multiple clinically relevant venetoclax-resistant mutants, including G101V, D103E/V/Y, F104L, A113G, R129L and V156D.
KRAS Q61H mutation has been found in pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC) among other solid tumors. In healthy cells, RAS proteins switch between ON and OFF states during signal transduction, but in cancer, mutations in RAS genes or regulators install RAS proteins in ON state permanently.
Researchers from Abbvie Inc. recently presented the discovery and preclinical evaluation of a novel CD19-targeting glucocorticoid receptor modulator (GRM) agonist antibody-drug conjugate (ADC), ABBV-319, being developed for the treatment of B-cell malignancies.
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