New Compound Shows Promise in Preventing Resistance to Lung Cancer Therapies
Non-small cell lung cancer (NSCLC), accounting for 80% of all lung cancer cases, frequently enough carries the KRAS mutation, present in 30% of NSCLC patients. This mutation is linked to reduced survival rates and the development of therapy resistance.
Recent research from US scientists has identified a potential solution: a compound called RPT04402. The study, published in the Journal of Clinical Inquiry, reveals that RPT04402 can be used in conjunction with existing cancer drugs to prevent the development of resistance in KRAS-mutated NSCLC.
The research focused on Protein phosphatase 2A (PP2A), a protein that inhibits lung cancer development. The study found that current drugs like Adagrasib and Trametinib,while initially effective,destabilize PP2A,leading to eventual resistance. However, the addition of RPT04402 stabilized the PP2A complex, inducing cancer cell death.
These findings were validated in mouse models, demonstrating tumor shrinkage and a significantly extended treatment duration – exceeding 150 days – when RPT04402 was combined with Adagrasib or Trametinib.
While acknowledging that further research is needed to determine efficacy across all NSCLC cases (currently estimated to apply to 20-30% of cases),the team is preparing to launch clinical trials in collaboration with Spring Works Therapeutics and Merck. Future studies will also explore the potential of this drug combination for treating KRAS-mutated pancreatic and colorectal cancers.