Novel PDE6δ inhibitors for the treatment of K-Ras mutant pancreatic cancer

Pancreatic cancer continues to pose significant challenges in the field of oncology, with dismal survival rates and limited treatment options. Patients diagnosed with this aggressive malignancy often face an uphill battle, with a five-year relative survival rate of just 11%.

Ras proteins are well-known as pivotal regulators of cell growth, proliferation, and differentiation, with their dysfunction implicated in various cancers (Brunsveld et al., 2006; Gelb et al., 2006). Among the Ras isoforms, K-Ras is the most commonly mutated, occurring in over 90% of pancreatic cancers (Cox et al., 2014) and representing an ideal target for the treatment of this type of cancer.

However, despite substantial research efforts, finding clinically useful drugs to target oncogenic Ras proteins has remained elusive, and treatment options for patients with pancreatic cancer remain limited.