A Computational Study of Efficient Combinations of FDA-Approved Drugs and Dietary Supplements in Endometrial Cancer

Madhurima Mondal, Aditya Lahiri, Haswanth Vundavilli, Giuseppe Del Priore, Norman Peter Reeves, Aniruddha Datta

Abstract: Endometrial cancer (EC) develops in the uterine lining, and in 2024, there will be approximately 67,880 reported cases of uterine cancer in the USA, with 90% of them being EC. Many unfit or elderly cancer patients are unable to undergo standard treatments for EC such as surgery, chemotherapy, or radiation therapy. For such patients, targeted therapies and immunotherapy drugs that have received approval from the FDA and have demonstrated significant efficacy in treating EC, offer a viable alternative. Dietary supplements, which are known for their lower toxicity, are increasingly becoming a complementary treatment option, alongside conventional primary therapies for patients battling many cancers. Additionally, individuals with a family history of EC or those focused on maintaining their overall well-being often include these supplements in their daily diet as a proactive measure. However, the consumption of random inefficient supplements may elevate the risk of other health issues, such as headaches, nausea, and fatigue. Since combination therapy has been already shown to be a successful treatment for EC, it makes sense to consider finding the optimal combinations of targeted therapies and dietary supplements in treating EC. This paper uses a Boolean Network approach to find such combinations. Our computational analysis predicts that combining Pembrolizumab (FDA-approved immunotherapy for EC) with dietary supplements like Epigallocatechin Gallate (EGCG), Melatonin, Curcumin, and Baicalein significantly enhances its efficacy, showing improvements ranging from 71.22% to 99.99% across different combinations. This demonstrates the potential for synergistic effects when supplements are combined with a commonly used immunotherapy treatment (Pembrolizumab) in EC.