About 15% of all cancers have co-deletion of both the MTAP and CDKN2A genes, which results in sensitization to MAT2A inhibitors, thus opening a therapeutic window in these cancer types. MAT2A inhibitors have demonstrated efficacy in MTAD-deficient cancers. Shouyao Holdings (Beijing) Co. Ltd. has developed and released data for their MAT2A inhibitor SY-9453 for the treatment of MTAP-deficient cancers.
Tissue factor (TF), a transmembrane protein overexpressed in tumors such as cervical, head and neck, NSCLC, and pancreatic cancers, initiates the extrinsic coagulation pathway under normal subendothelial expression. TF-targeted vedotin antibody-drug conjugates (ADCs) are in clinical evaluation for solid tumors, but toxicities, including peripheral neuropathy, ocular effects and epistaxis, limit their use.
Tumors with high levels of microsatellite instability (MSI-H), such as some subsets of colorectal, endometrial and gastric cancers, are associated with a hypermutated phenotype and a specific dependency on the WRN gene. Pharmacologic inhibition of WRN has been shown to selectively impair the viability of MSI-H cancer cells, effectively blocking tumor growth while sparing microsatellite-stable (MSS) cells.
About 15% of all cancers have co-deletion of both the MTAP and CDKN2A genes, which results in sensitization to MAT2A inhibitors, thus opening a therapeutic window in these cancer types. MAT2A inhibitors have demonstrated efficacy in MTAD-deficient cancers. Shouyao Holdings (Beijing) Co. Ltd. has developed and released data for their MAT2A inhibitor SY-9453 for the treatment of MTAP-deficient cancers.
Peptide-drug conjugates (PDCs) are emerging as a promising alternative to antibody-drug conjugates (ADCs), offering enhanced tumor penetration and reduced immunogenicity. Carbonic anhydrase IX (CAIX) and epidermal growth factor receptor (EGFR) are both well-validated targets in oncology due to their role in cancer cell survival, invasion and migration.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important factor from a complex downstream of Bruton tyrosine kinase (BTK) in the B-cell receptor (BCR) signaling pathway.
Acute myeloid leukemia (AML) harboring KMT2A rearrangements (KMT2A-r) represents a highly aggressive disease subtype, characterized by poor therapeutic response and a high risk of relapse.
DNA damage repair enzymes are interesting targets in cancer, since genomic instability and DNA repair defects are important cancer cell hallmarks. Poly (ADP-ribose) glycohydrolase (PARG) is the dominant eliminator of PARylation in the cell, the activity of which prevents excessive accumulation of PARylation, and promotes the dissociation of repair proteins, as well as ensuring the smooth completion of DNA repair process.
