Researchers from Fudan University and their collaborators reported the synthesis and preclinical characterization of novel Bruton’s tyrosine kinase (BTK)-targeting proteolysis-targeting chimeras (PROTACs) based on ARQ-531, a potent, reversible, noncovalent BTK inhibitor.
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.
Werner syndrome ATP-dependent helicase (WRN) is an enzyme involved in DNA replication and repair and has been identified as a synthetic lethality target in tumors with high microsatellite instability (MSI-H).
Microsatellite instability (MSI), which results from defects in the DNA mismatch repair system, is an important biomarker in colorectal cancer. While the MSI-high (MSI-H) status predicts response to pembrolizumab, a commonly used immune checkpoint inhibitor in metastatic colorectal cancer, a subset of MSI-H patients still does not respond to this treatment.
KAT6A and its paralogue KAT6B are histone acetyltransferases whose overexpression is linked to poor prognosis in ER+/HER2- breast cancer and other types of tumors.
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