A Personalized Real-time Model of Drug Resistance in Gynecological Cancers: Not to Leave CAF Unturned

Abstract

Evidence suggests the involvement of cancer-associated fibroblasts (CAFs) in developing treatment resistance in various solid tumors. These findings emphasize the importance of understanding the biology and function of CAFs in the context of therapy resistance to develop improved treatment strategies for these solid tumors. The function of CAFs in promoting therapy resistance is organ-type specific. In the published literature, we observed an organ-type-specific imbalance regarding CAF’s role in endometrial neoplasms. Here we present a commentary on the innovative and promising approach to studying endometrial and ovarian CAFs in therapy resistance. Our personalized real-time model allows a more comprehensive understanding of CAFs' involvement in developing resistance to specific drugs or combinations. By adopting a tumor-tumor microenvironment (TME) holistic approach, we recognized the importance of studying tumor cells and the surrounding TME to understand disease progression better. Our CAF-based Two-Cell Hybrid Co-Culture model established using CAFs from resected tumor tissue from patients with gynecological cancers provides a relevant and patient-specific context for testing drug resistance. This personalized real-time model has the potential to shed light on the mechanisms by which CAFs contribute to therapy resistance. By studying the interactions between tumor cells and CAFs in this model, one can gain valuable insights into the role of CAFs in driving resistance and identify potential therapeutic targets to overcome it.