The Chinese National Institute of Pharmaceutical R&D Co. Ltd. has described sulfonamide compounds acting as tyrosine-protein phosphatase non-receptor type 11 (PTPN11; PTP-2C; SHP-2) inhibitors reported to be useful for the treatment of diabetes, obesity, cancer, Noonan and LEOPARD syndromes.
Among over 100 members of the PTP family, protein-tyrosine phosphatase 1B (PTP-1B) and T-cell protein-tyrosine phosphatase (PTPN2, TCPTP) have the most closely related homology (72%), sharing identical catalytic subunits. Significantly, together they serve nonredundant functions suppressing CD8+ T-cell activation and negatively impacting on tumor cells antigen presentation. Agents that can simultaneously target both PTP-1B and TCPTP have the potential to provide therapeutic benefits in the context of cancer and/or diabetes by increasing T-cell activation and reversing suppression of tumor cell MHC1 expression.
Expression of the tyrosine-protein phosphatase non-receptor type 22 (PTPN22) is restricted to hematopoietic cells where it serves critical functions in regulating T-cell signaling that have made PTPN22 the focus of potential future cancer immunotherapy.
Researchers from Astrazeneca plc described the development and preclinical evaluation of AZD-5335, a novel antibody-drug conjugate (ADC) consisting of folate receptor α (FR-α)-targeting antibody conjugated to a proprietary topoisomerase 1 inhibitor (TOP1i), being developed as a potential new therapeutic against ovarian cancer.
Men with advanced prostate cancer only have a 5-year survival rate of 28%, mainly due to resistance to therapy. Enolase-1 (ENO1), also known as α-enolase, is a glycolytic enzyme with promise as a target for treating neuroendocrine prostate cancer (NEPC) and an alternative to prostate-specific member antigen (PSMA) targeting.
Tumor-associated calcium signal transducer 2 (TROP2) is a promising therapeutic target due to its high expression observed in several solid tumors. Investigators from Jiangsu Hengrui Pharmaceuticals Co. Ltd. have reported preclinical data on the anti-TROP2 antibody-drug conjugate (ADC) SHR-A1921 for the potential treatment of non-small-cell lung cancer (NSCLC).
At the ongoing AACR meeting, Amgen Inc. provided details on the discovery and preclinical characterization of AMG-305, a novel dual-targeting bispecific T-cell engager (BiTE) molecule, being developed as a potential new anticancer agent. While BiTE molecules offer a targeted immune therapy approach to treat cancer, on-target toxicity from normal tissue target expression has been a key issue in the development of T-cell engager molecules in solid tumors.
Heterogeneity, in both tumors and their microenvironment, limits the success of current cancer treatments. But it also provides opportunities. Heterogeneities “are not barriers to therapy, they are vulnerabilities to be exploited,” was how David DeNardo described his take at the 2023 annual meeting of the American Association for Cancer Research (AACR) on Sunday.
Esophageal squamous cell carcinoma (ESCC) is a common malignant subtype of esophageal cancer that predominantly occurs in East Asian countries. Although genomic aberrations and highly mutated genes, such as TP53, have been identified in advanced stages, the first occurrence of mutations and their related effects during ESCC carcinogenesis remain poorly understood.
Research at Incyte Corp. has led to the development of hetero-tricyclic compounds acting as GTPase KRAS (mutant) inhibitors and thus reported to be useful for the treatment of cancer, inflammatory and immunological disorders.
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