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Published on: February 7, 2021
Cancer mutation profiles predict ICIs efficacy in patients with non-small cell lung cancer
Liping Zhu1, Dafu Ye2, Tianyu Lei2
1Department of Medical Oncology, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, Shandong Province, People's Republic of China.
Abstract:
Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.
Insights
Cancer mutation profiles, especially co-mutations, are crucial for predicting non-small cell lung cancer (NSCLC) patient response to immune checkpoint inhibitors (ICIs). Understanding these profiles can optimize personalized immunotherapy strategies.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) show promise in non-small cell lung cancer (NSCLC) but have limited response rates.
- Current methods for assessing treatment response are insufficient for predicting long-term benefits.
- Effective biomarkers for identifying responsive NSCLC patients to ICIs are scarce.
Purpose of the Study:
- To review the role of cancer mutation profiles in predicting immunotherapy efficacy in NSCLC.
- To analyze the underlying mechanisms of how mutation profiles influence treatment response.
- To provide insights for optimizing individualized NSCLC therapy based on mutation status.
Main Methods:
- Literature review and analysis of existing studies on gene mutations and immunotherapy response.
- Examination of co-mutation patterns and their impact on the tumor microenvironment.
- Exploration of signaling pathways affected by co-mutations in anti-tumor immunity.
Main Results:
- Single gene mutations have limited predictive power for immunotherapy response.
- Co-occurring mutations significantly alter the tumor microenvironment phenotype.
- Co-mutations can synergistically activate or suppress anti-tumor immune responses.
Conclusions:
- Cancer mutation profiles, particularly co-mutations, are vital for predicting ICI efficacy in NSCLC.
- Identifying specific mutation profiles can help screen patient subgroups likely to benefit from immunotherapy.
- This knowledge can guide the development of personalized therapeutic strategies for NSCLC.
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