Ella Rahimo
Research Mentor: Siva Kumar Natarajan
Mentor Department: Department of Pathology, Medicine
Author(s): Ella Rahimo, Siva Kumar Natarajan
Session: Session 5 (2:00 PM – 2:50 PM)
Presentation Type: Poster 79
Abstract
Prostate cancer is one of the most frequently diagnosed cancers in men worldwide and remains a leading cause of cancer-associated death, specifically in advanced cases of this metastatic disease. While localized prostate cancer is often treatable, the disease progression can be linked to metabolic adaptations that support sustainable growth and resistance to therapy. Prostate cancer cells exhibit extreme metabolic plasticity, including the ability to alter glucose utilization and increase reliance on glycolytic pathways despite the presence of oxygen. A key feature of these cells’ metabolic reprogramming ability is the enhanced lactate production which is driven by lactate dehydrogenase (LDH), which converts pyruvate to lactate and regenerates NAD+ in the glycolytic pathway. Increased hypoxia and lactate production are associated with prostate cancer progression. However, how lactate drives this aggressive phenotype in prostate cancers is unknown. This research project aims to understand the tumor-driving roles of lactate and to specifically examine if lactate production by LDH promotes resistance to therapies targeting androgen signaling in these tumors. Preliminary data from the Cancer Dependency Map (DepMap) portal show that prostate tumors are uniquely sensitive to inhibition of both the androgen receptor (AR) and LDH. Based on this observation, it is hypothesized that lactate derived from LDH plays a role in AR signaling. This project tests this hypothesis by treating a panel of patient-derived prostate cancer cell lines with a pharmacological inhibitor of LDH. Additionally, the study will test whether LDH inhibition sensitizes prostate cancer cells to AR signaling inhibitors.
