The North Carolina non-profit Lung Cancer Initiative has awarded Duke Cancer Institute member Chuan-Yuan Li, DSc, a professor in the Duke University School of Medicine Departments of Pharmacology and Cancer Biology and Dermatology, the Vicky Amidon Innovation in Lung Cancer Research Award.
The $50,000 grant will support Li's ongoing investigations into whether specific FDA-approved cholesterol control drugs may be repurposed in the treatment of LKB1/STK11-mutated advanced non-small cell lung cancer (NSCLC) to help these patients overcome immunotherapy drug resistance.
The importance of cholesterol in transforming normal cells into cancer cells, the role of cholesterol in cancer spread, and the utility of cholesterol control in cancer control, are topics of current study and debate in a number of cancer types and by a number of cancer researchers.
Based on work published last year (Liu et al, Nature, 2020), Li suspects that PCSK9 — a protein that regulates the amount of cholesterol in the bloodstream and that’s found in high amounts in LKB1/STK11- mutated advanced NSCLC tumors — is driving the immune evasion of this type of lung cancer and that the protein may play a key role in these patients' known resistance to immune checkpoint inhibitor drugs, a type of immunotherapy that’s shown great promise in many but not most patients with advanced lung cancer. (Numerous factors, including drug resistance, have limited their efficacy)
“Our hypothesis is that using certain FDA-approved cholesterol control drugs — specifically evolocumab (Repatha) or alirocumab (Praluent), which are designed to inhibit the functioning of PCSK9 proteins — may also work in advanced LKB1/STK11-mutated tumors,” Li explained. “Inhibiting the functioning of PCSK9 may help these particular non-small cell lung cancer patients — which represent 25 to 30% of all cases of advanced NSCLC — overcome their resistance to immune checkpoint inhibitor drugs and thus receive a greater benefit from these drugs.”
Li noted that the cholesterol control drugs evolocumab and alirocumab have shown minimal toxicity in human cardiology patients, which makes him hopeful about the potential side effects of these drugs if used in cancer patients. (Statins, a popular, but different kind of cholesterol control drug, limit the liver’s production of cholesterol by blocking a protein that the body needs to produce cholesterol — HMG-CoA-Reductase — and help the body reabsorb existing cholesterol. Statins are not part of Li’s LCI-funded research project.)
In addition to lab studies to further understand the role PCSK9 in LKB1/STK11-mutant lung cancer, Li hopes to collaborate with DCI immunotherapy researchers Scott Antonia, MD, PhD (director of the DCI Center for Cancer Immunotherapy), Neal Ready, MD, PhD and James Isaacs, MD, to evaluate evolocumab through phase I and II clinical trials.
Lung cancer claims more lives in North Carolina and the US, annually, than any other cancer and more than breast, colon, and prostate cancers combined. According to LCI, an estimated 8,830 individuals in North Carolina were diagnosed with lung cancer in 2021.
Since 2008, LCI has funded more than $2.8 million in lung cancer research through programs like the Research Fellows Program, the Health Disparities in Lung Cancer Grant (in partnership with the V Foundation for Cancer Research), an annual Career Development Grant, and research innovation grants. Duke Cancer Institute has been a direct recipient of about $875,000 of these grants.
Li’s grant award from LCI — the Vicky Amidon Innovation in Lung Cancer Research Award— is named in memory of Vicky Amidon a beloved wife, mother, and friend who lost her battle with lung cancer at the age of 46 and whose memory is furthered through her family’s advocacy and support for the advancement of lung cancer research and awareness. The award, first given in 2019, recognizes and supports researchers who are developing innovative lung cancer projects that will improve the lives of those at risk of or living with lung cancer.