Oncogene-addicted solid tumors and microbiome-lung cancer as a main character: a narrative review

Abstract

Background and objective: Lung cancer stands as the main cause of cancer-related deaths worldwide. With the advent of immunotherapy and the discovery of targetable oncogenic driver genes, although prognosis has changed in the last few years, survival rates remain dismal for most patients. This emphasizes the urgent need for new strategies that could enhance treatment in precision medicine. The role of the microbiota in carcinogenesis constitutes an evolving landscape of which little is known. It has been suggested these microorganisms may influence in responses, resistance, and adverse effects to cancer treatments, particularly to immune checkpoint blockers. However, evidence on the impact of microbiota composition in oncogene-addicted tumors is lacking. This review aims to provide an overview of the relationship between microbiota, daily habits, the immune system, and oncogene-addicted tumors, focusing on lung cancer.

Methods: A PubMed and Google Scholar search from 2013 to 2024 was conducted. Relevant articles were reviewed in order to guide our research and generate hypothesis of clinical applicability.

Key content and findings: Microbiota is recognized to participate in immune reprogramming, fostering inflammatory, immunosuppressive, or anti-tumor responses. Therefore, identifying the microbiota that impact response to treatment and modulating its composition by interventions such as dietary modifications, probiotics or antibiotics, could potentially yield better outcomes for cancer patients. Additionally, targeted therapies that modulate molecular signaling pathways may impact both immunity and microbiota. Understanding this intricate interplay could unveil new therapeutic strategies.

Conclusions: By comprehending how microbiota may influence efficacy of targeted therapies, even though current evidence is scarce, we may generate interesting hypotheses that could improve clinical practice.

Keywords: Lung cancer; microbiome; oncogene-addicted tumor; targeted therapies.

Figure 1

Dysbiosis of gut microbiota impacts lung and tumor microenvironment, conditioning immune reprogramming. MR, mineralocorticoid receptor; LXRα, liver X receptor α; Treg, regulatory T cell; IL-10, interleukin 10; TGF-β, transforming growth factor beta.

Figure 2

Gut and lung microbiota composition in lung cancer patients, as compared with healthy subjects.

Figure 3

Interactions between dietary habits and interventions, the microbiota, the immune system, and their impact on cancer cells and the TME. TME, tumor microenvironment.