128P - Network medicine approach identifies small molecule drugs as immune checkpoint inhibitors repurposable for rectal cancer

Background

Rectal cancer (RC) is a significant health concern, ranking as a prevalent form of colorectal cancer, which is third most common cancer diagnosed in both men and women in the United States. The estimations for 2023 project 106,970 new cases of colon cancer and 46,050 new cases of RC, highlighting the urgency to develop potential therapies for RC. Here, a network-based drug repurposing strategy was devised to identify drugs with the potential for repurposing as immune checkpoint inhibitors specifically for RC.

Methods

The study involved constructing a network of RC-associated immune checkpoint proteins (ICPs) and their induced protein interactions (P-ICP). Through network analysis, key target genes closely interacting with ICPs were identified. This was followed by network proximity analysis in the drug-target interaction (DTI) network and pathway cross-examination to identify potential immune checkpoint inhibitors among 109 distinct pathways associated with approved drugs.

Results

The developed approach successfully predicted 19 FDA-approved drugs with potential to target RC-associated ICP-induced pathways. Notably, three of these drugs including Bevacizumab, Cetuximab, and Capecitabine have already been utilized in RC treatment, validating the effectiveness of the strategy. Furthermore, six of the predicted drugs possess immunomodulatory properties, highlighting their potential in immune-related therapeutic applications. The analysis categorized the predicted pathways into two distinct groups: 13 immune pathways and 88 metabolic pathways, indicating the drugs' versatility in targeting different aspects of RC.

Conclusions

The network-based drug repurposing strategy presented in this study offers new opportunities for the rapid repurposing of FDA-approved medications in clinical trials for EC treatment. The identification of 19 drugs with potential immune checkpoint inhibitor properties and insight into useful drug combinations through drug-drug correlation analysis provide valuable contributions to the search for effective therapies against RC. These findings pave the way for further investigations and expedited development of potential treatments for this prevalent cancer type.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

This work was supported by the National Research Foundation (NRF), Korea, under project BK21 FOUR.

Disclosure

All authors have declared no conflicts of interest.