Checkpoint kinase 1 (CHK1) is involved in cell cycle arrest by activation of DNA damage response pathways. The aim of researchers from Shanghai Fosun Pharmaceutical (Group) Co. Ltd. was to develop a potent oral CHK1 inhibitor, XS-02, for the treatment of solid tumors.
Thetis Pharmaceuticals LLC and Harvard Medical School have presented data on the stable salt chelate of Resolvin E1, TP-317, for the potential treatment of immune checkpoint inhibitor (ICI)-resistant and sensitive tumors. TP-315 is an activator of ChemR23, a receptor expressed on immune cells in the tumor microenvironment. In vivo murine models of lung, melanoma (B16F10) and pancreatic (Panc2-H7) tumors were used to investigate TP-317 monotherapy and in combination with ICI.
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.
