A new oncogenic function of the glycolytic enzyme lactate dehydrogenase-A in small cell lung cancer
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Abstract
Small Cell Lung Cancer (SCLC) is an epithelial cancer that has, until recent years, been labeled a recalcitrant tumor type. Since its discovery and classification, there has been very little research to understand and treat SCLC. Conventional methods of treatment for SCLC include chemotherapeutics have been used with little long-term success. Following initial treatment, the cancer appears to be fully wiped out, however seemingly without fail the cancer reemerges with acquired drug resistance and the capability to rapidly metastasize, leading to a five-year survival rate of less than 10%. While there have been continuous improvements in the field of cancer therapeutics, combining chemotherapeutics and immunotherapy, there has been no targeted clinical therapy for SCLC. Recent studies have suggested that an acidic tumor microenvironment is highly important for the progression of other cancers. LDHA generates lactate from pyruvate, leading to a more acidic environment, which indicates LDHA may be a viable target for cancer therapeutics. CRISPR-cas9 gene editing and mouse SCLC cell lines were used to study lactate concentration and cell vitality. After analysis of several different SCLC tumors, larger tumors had both a higher metastatic capability and higher concentrations of lactate, indicating that LDHA was more highly active in these tumors. CRISPR-cas9 knockout targeting of LDHA decreased SCLC colony formation and cellular growth in vitro, leading to the conclusion that LDHA may play a vital role in the future as a potential therapeutic target for the treatment of SCLC.
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Attribution 4.0 International