Personalized Treatment Strategies for Lung Cancer

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy for various kinds of cancer, including lung cancer. However, there are several limitations of ICIs including immune-resistance, immune-related adverse events (irAEs), and heterogeneity in patient responses to ICIs. Since ICIs can cause serious adverse events and fatalities, personalized prediction of ICI response is becoming increasingly important. This aspect remains a challenge due to the patient’s immune system, the tumor microenvironment, and the complex interplay of factors influencing treatment efficacy. Lung cancer is the leading cause of cancer-related death in the U.S. and globally. According to the Centers for Disease Control and Prevention, it is the third most common cause of cancer in the nation . and nearly 131,000 patients died from lung cancer in 2022. Moreover, since the five-year survival rate for lung cancer patients is only 22 percent, improved treatment methodologies are urgently needed. The two main categories of lung cancer, according to the World Health Organization, are small-cell lung cancer and non-small-cell lung cancer (NSCLC). Of these, the latter constitutes 80 percent of lung cancer cases.

Current treatment strategies for NSCLC include surgical resection, chemotherapy, radiotherapy, targeted drug therapy and immunotherapy. Compared to other methods, immunotherapy (which includes ICIs, cancer vaccines and cellular immunotherapies) is effective across a broad patient population and has a tolerable safety profile. In many cases, immunotherapy is combined with other treatment modalities for greater efficacy. Most metastatic NSCLC patients receive ICIs in combination with chemotherapy. However, many ICI-treated patients do not receive positive outcomes and about 87 percent suffer various irAEs, which affect the gastrointestinal tract, endocrine glands, skin, and liver. Some irAEs are fatal, which underscores the importance of personalized ICI treatment response prediction. “Our study provides proof-of-concept evidence that plasma cfDNA 5hmC can accurately predict an ICI treatment response in lung cancer. The use of novel and innovative markers to guide ICI therapy may improve the precision and effectiveness of treatment while reducing adverse effects. While further studies are needed to fully understand its role in ICI treatment response, cfDNA 5hmC signatures could offer a powerful, highly sensitive, and minimally invasive tool for guiding the clinical management of lung cancer patients,” said Li. The economic burden of lung cancer is significant. Lung cancer leads to significant societal and financial burdens for patients, caregivers and health insurance organizations. The per-patient annual cost of medical services for lung cancer patients ranges from 12,200 to 118,000. . “The accurate prediction of ICI treatment response can help avoid unnecessary side effects and financial burdens for patients,” Li added.

Jianming Shao, Yitian Xu, Randall J Olsen, Saro Kasparian, Kai Sun, Sunil Mathur, Jun Zhang, Chuan He, Shu-Hsia Chen, Eric H Bernicker, Zejuan Li. 5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer. Cells. 2024 Apr 19;13(8):715. doi: 10.3390/cells13080715. This work was supported by an American Cancer Society Research Scholar Grant RSG-17-044-01-LIB (Z.L.).