Four years after the COVID-19 pandemic in China, researchers are optimistic about possible development of a drug under development to treat underlying genetic mutations in the disease, such as that driving cancer.
The drug candidate, called Sah1-88 and developed by Shanghai General Hospital and ShanghaiTech Biological Engineering Research Institute (TECHRI), could help battle lyutein, a protein driving the progression of many types of cancer, according to research published online March 30 in the journal Cell Reports.
“Lyutein is one of the most common proteins in lung cancer cells and is mutated in approximately eight to nine percent of therapeutically-tolerant patients, ” says main author Michael Wilson, Ph. D., a member of Shanghai General’s Chang Gung School of Medicine and Shanghai Tech National Cancer Institute. “In the event of this pandemic or need to treat it, we would think that, if Sah1-88 could be used, it could essentially be used for preventing recurrence or treating relapses. “
Indeed, while there is a near 100 percent response rate to lyutein inhibitors in the clinical setting, time to clinical benefit and long-term survival poses challenges.
To accomplish this objective, the researchers developed a compound with a better anti-LDL survival ratio and a cut-off time before tumor growth banks indicate pyroptosis, an abnormal cell growth above the nucleus that predisposes to cancer cells overexploid. Short-term treatment with lyutein and bispecific lyutein inhibitors in mice causes Lyutein to return to equilibrium, leading to a 70 percent reduction in tumor size.
Wilson and co-author Michael Callaghan, Ph. D., an assistant professor at TECHRI, report that they screened an additional 20 compounds for potential toxicity against lyutein and found that all of the compounds showed an anti-LYP2 blockade and an equivocal survival value (ESR), possibly indicating some relevance to clinical trials.
“The safety profile and ESR of each compound in mice is similar, and the ones that showed an equivocal survival value (SSR), were the ones most likely to be effective, ” says Wilson. “They do have some effects that hearken back to three weeks of toxicity in humans. “
Though the potential therapeutic effect is exciting, limitations remain such as a lack of studies in more complex cells that more closely mimic human tumor tissues. Further, the TECHRI-led effort to develop and validate a drug that effectively targets lyutein appears to be overlapping with efforts by a group of several labs all from Shanghai, including ShanghaiTech’s Advanced Research & Development Department, that have developed similar compounds with “high-throughput screening. “
Still, the amount of toxic with respect to lyutein “is not something that stands out as being particularly high given the positive results that we have seen so far, ” explains Wilson. “It’s not something that would be useful in patients and it makes us very nervous. “
Future research should explore the combination of axon guidance and anticancer drugs used against lyutein, he says.