This molecule, called ACBI3, could potentially lead to new therapies independent of KRAS mutation type, improving outcomes for all patients with cancers caused by KRAS mutations.
This molecule, called ACBI3, could potentially lead to new therapies independent of KRAS mutation type, improving outcomes for all patients with cancers caused by KRAS mutations. The research is published in reputed journal Science.
Potential treatment for millions of cancer patients
KRAS is the most mutated gene in cancer with mutations occurring in 17%–25% of all cancers, affecting millions of patients worldwide. It plays a crucial role in tumour growth, as it is important for driving uncontrolled proliferation of tumour cells. Targeting KRAS function is a primary focus of cancer drug discovery. However, currently approved treatments can only address one of many KRAS gene mutations, called G12C, leaving more than half of patients with cancers driven by KRAS without a targeted treatment option.
The molecule ACBI3 developed by multi-disciplinary teams in the laboratory of Professor Alessio Ciulli and Boehringer Ingelheim is based on a class of small molecules called PRoteolysis TArgeting Chimeras (PROTACs). ACBI3 has been shown to be able to rapidly eliminate 13 out of the 17 most common KRAS mutants with high potency and selectivity. KRAS degradation by ACBI3 was also more efficacious than using KRAS small molecule inhibition, and induced effective tumour regression in mouse models, validating KRAS degradation as a novel therapeutic concept.
Read more at: University of Dundee
