Metformin improves survival in patients with concurrent diabetes and small cell lung cancer: a meta-analysis

Small cell lung carcinoma (SCLC) is an aggressive and difficult to treat cancer. Although immunohistochemistry is not mandatory for a SCLC diagnosis, it might be required, especially in small samples. Insulinoma-associated protein 1 (INSM1) is expressed in endocrine and nervous tissues during embryogenesis, generally absent in adults and re-expressed in SCLC and other neuroendocrine neoplasms. Its high specificity propelled its use as diagnostic biomarker and an attractive therapeutic target. Herein, we aim to provide a systematic and critical review on the use of INSM1 for diagnosis, prognostication and the treatment of SCLC. An extensive bibliographic search was conducted in PubMed® focusing on articles published since 2015. According to the literature, INSM1 is a highly sensitive (75–100%) and specific (82–100%) neuroendocrine immunohistochemical marker for SCLC diagnosis. It can be used in histological and cytological samples. Although advantageous, its standalone use is currently not recommended. Studies correlating INSM1 expression and prognosis have disclosed contrasting results, although the expression seemed to entail a worse survival. Targeting INSM1 effectively suppressed SCLC growth either as a suicide gene therapy regulator or as an indirect target of molecular-targeted therapy. INSM1 represents a valuable biomarker for a SCLC diagnosis that additionally offers vast opportunities for the development of new prognostic and therapeutic strategies.

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Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania

Jonusas,

Patasius,

Drevinskaite

et al. 2024

Medicina

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Background and Objectives: This study aimed to evaluate the potential chemopreventive effect of antidiabetic medications, specifically metformin and pioglitazone, on lung cancer in patients with type 2 diabetes mellitus (T2DM). Additionally, the potential dose–response relationship for metformin use was analyzed. Methods: We conducted a retrospective cohort study utilizing comprehensive national health insurance and cancer registry databases to gather a large cohort of T2DM patients. Cox proportional hazards regression models were used to assess the risk of lung cancer across different antidiabetic medication groups, adjusting for potential confounders such as age and gender. A dose–response analysis was conducted for metformin users. Results: Our results indicated that metformin users had a significantly lower lung cancer risk than the reference group (HR = 0.69, 95% CI [0.55–0.86], p = 0.001). The risk reduction increased with higher cumulative metformin doses: a metformin cumulative dose between 1,370,000 and 2,976,000 had an HR of 0.61 (95% CI [0.49–0.75], p < 0.001) vs. cumulative metformin dose >2,976,000 which had an HR of 0.35 (95% CI [0.21–0.59], p < 0.001). No significant association between pioglitazone use and the risk of lung cancer was found (HR = 1.00, 95% CI [0.25–4.02]). Conclusions: This study shows that metformin may have a dose-dependent chemopreventive effect against lung cancer in T2DM, while the impact of pioglitazone remains unclear and requires further investigation.

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Metformin improves survival in patients with concurrent diabetes and small cell lung cancer: a meta-analysis

Cited by 3 publications

References 34 publications

Body Mass Index is related to short-term retinal worsening in type 2 diabetes mellitus patients treated with anticancer drugs

Body Mass Index is related to short-term retinal worsening in type 2 diabetes mellitus patients treated with anticancer drugs

Insulinoma-Associated Protein 1 (INSM1): Diagnostic, Prognostic, and Therapeutic Use in Small Cell Lung Cancer

Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania

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