P-glycoprotein (P-gp) is one of several ABC transporters that can pump drugs out of tumor cells and thereby render chemotherapy ineffective. Overexpression of P-gp can give rise to multidrug resistance, making cancers quite difficult to treat. Several inhibitors of P-gp have been described, but none has entered the clinic, mainly because of poor efficacy or adverse reactions.
Although tricomplex pan-RAS (ON) inhibitors, such as RMC-6236, constitute a promising class of therapeutics against RAS-driven cancers, their on-target, off-tumor toxicities challenge the dosing strategy and the safety of drug combinations.
Inactivation of the tumor suppressor p53 occurs in approximately half of human cancer cases. In particular, the Y220C point mutation, which induces p53 misfolding and inactivation, is found in about 1% of solid tumors. Previous research identified a unique, druggable pocket on the p53 surface created by this mutation that constitutes a promising cancer therapeutic target.
In glioblastoma multiforme, MTAP loss leads to MTA accumulation, which partially inhibits PRMT5, making the cells reliant on residual PRMT5 activity for survival. Targeting this remaining PRMT5 with MTA-cooperative inhibitors induces synthetic lethality, representing a promising targeted approach for MTAP-deleted gliomas. Researchers from Ryvu Therapeutics SA reported the preclinical profile of RVU-305, a PRMT5 inhibitor, in MTAP-deleted cancer models.
T-knife Therapeutics Inc. has filed a clinical trial application (CTA) to initiate a phase I trial of TK-6302, a PRAME-targeted T-cell receptor (TCR) T-cell therapy in solid tumors. Pending CTA approval, the ATLAS trial is planned to begin next year.
Captain T Cell GmbH has successfully closed an equity financing round to support its T-cell receptor (TCR) T-cell therapies for solid tumors. The company’s autologous lead program, CTC-127, is a best-in-class TCR T-cell therapy targeting MAGE-A4-positive solid tumors and is expected to enter clinical trials in early 2027.
Northridge Health Group (Hong Kong) Co. Ltd. has divulged proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety covalently linked to a tyrosine-protein phosphatase non-receptor type 2 (PTPN2; TCPTP) and/or tyrosine-protein phosphatase non-receptor type 1 (PTPN1; PTP-1B)-targeting moiety via a linker.
Type I protein arginine methyltransferases (PRMTs) are an attractive target for inhibiting growth of triple-negative breast cancer. Several small-molecule inhibitors of these enzymes are in various stages of preclinical development, while clinical trials of the inhibitor GSK-3368715 had to be terminated early because of poor efficacy and toxicity.
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