PARP1 is critical for repairing DNA single-strand breaks. First-generation PARP1/2 inhibitors have proven effective in the treatment of tumors with mutations in the essential homologous recombination repair (HR) genes including BRCA mutations. However, hematological toxicity associated with PARP2 emphasizes the need to find second-generation compounds with better safety profiles.

Researchers from Astrazeneca plc recently reported preclinical data for AZD-3470, a second-generation MTA-cooperative PRMT5 inhibitor currently in early clinical development for the treatment of patients with MTAP-deficient solid tumors (NCT06130553) and hematological cancers (NCT06137144).

Bruton tyrosine kinase (BTK) inhibitors are commonly used in the treatment of hematological cancers. However, approximately 67% of patients with relapsed chronic lymphocytic leukemia (CLL) develop resistance to acalabrutinib and ibrutinib due to mutations in BTK, initially most often C481S.

Hepatoblastoma is the most common pediatric liver cancer and has limited therapeutic options, with platin-based therapy showing severe side effects. WNTinib is a kinase inhibitor with specificity for β-catenin (CTNNB1)-mutated hepatocellular carcinoma (HCC) and is a therapeutic approach that shows promise for treating hepatoblastoma.

Methionine adenosyltransferase 2A (MAT2A), the rate-limiting enzyme in the methionine cycle, catalyzes the formation of S-adenosylmethionine (SAM) from methionine and adenosine triphosphate (ATP).

Cancer cells are exposed to stress and depend on a balanced integrated stress response (ISR) to survive in the context of uncontrolled growth.

The histone acetyltransferase KAT2A, and its paralog KAT2B have been identified as key drivers of tumor cell plasticity in small-cell lung cancer (SCLC). Researchers from Auron Therapeutics Inc. aimed to evaluate the novel KAT2A/B heterobifunctional protein degrader, AUTX-703, in models of SCLC.