Pancreatic ductal adenocarcinoma (PDAC) has a low 5-year survival rate of <12%. Even though KRAS is mutated in about 88% of PDACs, the KRAS G12C mutation is rare, limiting the use of KRAS G12C inhibitors. Hence, there is a need for pan-RAS inhibitors to cover the broad RAS mutation spectrum in PDAC.

Gene editing strategies, from epigenetic engineering to cell reprogramming and genetic vaccines, are accelerating the development of new therapies that awaken the immune system to treat cancer, as presented last month in Rome at the 31st Annual Congress of the European Society of Gene and Cell Therapy (ESGCT). Some of these advances are taking advantage of the conditions of the tumor microenvironment, where cancer cells coexist with immune cells, microorganisms and blood vessels.

The c-MYB oncogene plays a key role in hematopoietic cell differentiation and proliferation. Genetic abnormalities and dysregulation of MYB have been found in several cancers, including adenoid cystic carcinoma (ACC) (80% of cases), making it an attractive druggable target for ACC treatment.

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).