Identifying Different Metabolic Subtypes of Prostate Cancer for Early Therapeutic Assessment
Abstract
Patients with advanced prostate cancer (PCa) receive anti-androgens (Enzalutamide) as the first line of treatment. Unfortunately, many patients develop resistance, and the disease relapses with aggressive histology and metastatic castrate-resistant (mCRPC) phenotype. Treatment options for mCRPC patients are limited and continue to pose a significant oncological challenge. There is growing recognition that alterations in cell metabolism and reprogramming of metabolic pathways are key drivers of PCa aggressiveness, progression and eventual resistant to therapy. The overarching goal of this project is to develop metabolic imaging to target treatment strategies of different metabolic sub-types of PCa. Recent studies from our group have demonstrated that the tumor's metabolic profile that impacts anti-androgens response can be identified early on by using hyperpolarized Magnetic Resonance Imaging (HP-MRI). We also discovered that Monocarboxylate Transporter (MCT) is dysfunctional in mCRPC and may be a viable target for therapeutic intervention. In this research, we will employ HP-MRI and Positron Emission Tomography (PET) to interrogate both glycolysis and carnitine metabolism that is closely linked with fatty acid metabolism in PCa. We will evaluate the treatment response of Enzalutamide in clinically relevant patient derived mouse models of PCa. We will correlate imaging data with metabolomics, immunohistochemistry and transcriptome profile analysis of the ex vivo tissue samples to elucidate the metabolic drivers of resistance. In two of the resistant models, we will attempt to restore drug sensitivity by targeting Monocarboxylate Transporter (MCT) pathway and image this transformation from resistance to sensitization by performing HP-MRI and PET. If successful, this research will provide mechanistic insights to advance our knowledge about mCRPC tumors and validate the efficacy of targeting MCT protein for therapeutic benefit.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1212574
Entities
People
- Pratip Bhattacharya
Organizations
- The University of Texas MD Anderson Cancer Center