Exploring the Role of Physical Activity in Modulating Radiotherapy Resistance in Small Cell Lung Cancer DMS114 Cells

Abstract

Objective: To examine the influence of physical activity on the resistance to radiotherapy in small cell lung cancer (SCLC) DMS114 cells and to explore potential mechanisms that could enhance the radio sensitivity of these cells.

Background: Lung cancer remains the most morbid and deadly malignancy globally, with SCLC being particularly aggressive and difficult to treat. Despite the advent of immune checkpoint therapies, their effectiveness is limited to approximately 15% of SCLC patients. SCLC is characterized by rapid tumor invasion and progression, often leading to short remission periods following conventional treatments such as radiotherapy, where resistance develops swiftly and undermines long-term patient survival. Methods: This study focuses on the cellular mechanisms driving survival, proliferation, and metastasis in SCLC, with a specific examination of DMS114 cell lines. We investigate how regular physical activity, as a modifiable lifestyle factor, influences the biological behavior of these cells under radiotherapy. The study evaluates changes in cell viability, apoptosis rates, and expression of genes related to radio resistance before and after introducing exercise regimens in vivo and in vitro. Results: Initial findings suggest that physical activity can modulate several pathways associated with radio resistance. Cells derived from physically active models showed altered expression in key regulatory proteins and enhanced sensitivity to radiotherapy. The remission rates in these models were comparably higher, and the duration of remission extended beyond typical periods observed in non-active controls. Conclusion: The integration of physical activity may represent a novel approach to mitigating radiotherapy resistance in SCLC, potentially reversing resistance mechanisms and improving overall survival rates. This study underscores the need for comprehensive clinical trials to validate the impact of physical activity on treatment outcomes in SCLC patients and highlights the critical role of basic research in understanding the complex biology of SCLC and its treatment resistance