HER2 and Bcl-2 alterations in non-small cell lung cancer, biological and clinical significance, therapeutic perspectives: A literature review

Abstract

Relevance: Lung cancer remains one of the leading causes of cancer mortality worldwide. Accord-ing to WHO, more than 2.2 million new cases are detected annually, and the mortality rate exceeds 1.8 million. Despite advances in diagnostics and treatment, the prognosis for non-small cell lung cancer (NSCLC), especially in the late stages, remains unfavorable. Molecular genetic biomarkers play a significant role in improving diagnostics and choosing therapy. Bcl-2 and HER2 proteins, involved in regulating apoptosis and proliferation, may be associated with the aggressive course of NSCLC and resistance to therapy. Their study is relevant for the development of a personalized approach to the treatment of this disease.
The study aimed to assess the biological and clinical significance of HER2 and Bcl-2 alterations in non-small cell lung cancer and to analyze their impact on disease prognosis and the effectiveness of various therapeutic strategies.
Methods: The search for electronic medical sources was conducted in the PubMed, Web of Science, and Google Scholar databases using the keywords: “biomarkers,” “non-small cell lung cancer,” “diagnosis,” “prognosis,” and “survival.” The review included full-text articles in Russian and English, published over the past five years and available in open access, devoted to the role of biomarkers in lung cancer early detection and prognosis.
Results: The expression of Bcl-2 and HER2 plays a significant role in the pathogenesis of NSCLC. Bcl-2, a key regulator of apoptosis, is detected in 30-50% of patients and may be associated with tumor aggressiveness and improved survival, depending on histological subtype and disease stage. HER2 alterations are found in 1-30% of cases, more commonly in adenocarcinomas among non-smoking women, and are associated with poor prognosis and therapy resistance. Targeted therapies like venetoclax and HER2 inhibitors (trastuzumab, deruxtecan, pyrotinib) improve progression-free survival.
Conclusion: Bcl-2 and HER2 are promising biomarkers and therapeutic targets in NSCLC. Their study supports personalized treatment and should be integrated into clinical practice to improve outcomes.