Physical activity as a molecular modulator to enhance immunotherapy and drug sensitivity in the endometrial cancer–comorbidity continuum

Category	Detail
Condition	Endometrial Cancer (EC)
Key Mechanisms	Physical activity modulates tumor microenvironment, enhances drug sensitivity, and improves immunotherapy efficacy.
Target Population	Postmenopausal women with endometrial cancer and comorbid conditions such as hypertension and chronic kidney disease.
Care Setting	Clinical management of endometrial cancer with a focus on multimorbidity.

Physical activity enhances cytotoxic T cell infiltration and remodels the tumor microenvironment.
Exercise reduces Myeloid-Derived Suppressor Cells (MDSCs) and repolarizes Tumor-Associated Macrophages (TAMs).
Physical activity improves renal perfusion and normalizes tumor vasculature, enhancing drug delivery.
Comorbidities like hypertension and chronic kidney disease are active barriers to effective treatment in EC.
Personalized exercise prescriptions can optimize molecular responses and overcome multidrug resistance.

Consider molecular classification of endometrial cancer for tailored treatment strategies.

Incorporate physical activity as a non-pharmacological adjuvant in treatment plans for endometrial cancer.

Assess the impact of physical activity on treatment outcomes and comorbidity management.

Be aware of the systemic inflammatory burden and uremic toxins that may affect treatment efficacy.

Women with endometrial cancer and comorbid conditions.

Exercise can serve as a systems-level intervention to enhance therapeutic responses.

Differentiate between preventive and treatment-sensitizing roles of physical activity.
Utilize exercise to improve metabolic health and reduce inflammation in patients with comorbidities.

Clinical Scorecard: The Role of Physical Activity in Modulating Molecular Responses to Improve Immunotherapy and Drug Efficacy in Endometrial Cancer with Comorbid Conditions