Researchers from the University of California, San Diego School of Medicine (CA, USA) have discovered a pathway that causes chemotherapy and radiation resistance in aggressive tumors in some patients. They also identified a novel therapeutic drug that targets the pathway. The results were published recently in Nature Communications.
“It was previously known that RAF (a family of proteins that regulate cellular signaling) governs resistance to therapies. We discovered an undescribed role for RAF and learned precisely how it occurs in a broad range of cancers,” explained lead author Sunil Advani (University of California, San Diego School of Medicine). “The hope is to increase survival rates among patients with highly aggressive cancers.”
Cancer cells utilize the pathway to protect their DNA from damage. The research team utilized an inhibitory drug-like compound termed KG5, and were able to reverse the resistance tumors had developed to radiotherapy and certain classes of chemotherapy that induce genotoxic stress.
“We are taking the tumor’s defenses away by targeting this pathway. By developing this drug, we have the potential to enhance radiation sensitivity of cancer while sparing healthy tissue. This drug increases the DNA-damaging effects of radiation and certain chemotherapies,” added David Cheresh, principal investigator of the study based at the Moores Cancer Center at University of California, San Diego Health. “We essentially get more antitumor activity with less radiation or chemotherapeutic drug. This allows us to see the antitumor effect while reducing terrible side effects. We have seen this in pancreatic, brain and lung cancer cells both in cell culture and in tumors growing in mice.”
In terms of future research, the team aim to improve the radio-sensitizing properties and safety profile of KG5 in order to test it in patients.
“For patients with aggressive cancers, there may be no good options left,” concluded Advani. “Armed with this new approach, our goal is utilize such a drug to improve the clinical outcomes of some of the most widely used anticancer therapies.”