Metabolic Reprogramming in Prostate Cancer Therapy
About Metabolic Reprogramming in Prostate Cancer Therapy
- One hallmark of virtually all cancers, is a global reprogramming of metabolism. Metabolic changes may drive disease progression and metabolic factors may serve as therapeutic targets.
- Dr. Altieri and team are studying how metabolic changes affect tumor cell metastasis and are testing novel methods to target tumor cell metabolism for the treatment of prostate cancer.
- Mitochondria are the energy generating factories of the cell. The effect of targeting mitochondria on prostate cancer metastasis will be tested by treatment of preclinical prostate cancer models with molecules that block essential mitochondrial proteins.
- The potential for achieving therapeutic synergy by targeting mitochondria and the oncogenic PI3K pathway will be tested by combining mitochondrial-inhibitors with PI3K pathway-inhibitors in preclinical laboratory models.
- Mitochondria can be repositioned within the cell and the location of mitochondria is hypothesized to affect cellular functions. Whether the repositioning of mitochondria influences tumor cell metastasis will be tested in prostate cancer cell lines. Targeting mitochondrial repositioning in combination with targeting of integrin proteins that regulate metastasis by controlling cell-cell and cell-extracellular matrix interactions will be studied for potential therapeutic synergy.
- Finally, whether targeting mitochondrial metabolism can reverse resistance to anti-androgen therapy will be explored.
What this means for patients: Tumor cells have highly altered metabolism indicating that targeting various aspects of metabolism may block tumor cell growth. Dr. Altieri and team are studying the role of metabolic alterations in tumor metastasis and testing novel methods to target aspects of metabolism in single and combination therapeutic strategies. If successful, this project will lead to new therapies to treat and prevent metastatic prostate cancer.
Dario Altieri, MD (The Wistar Institute)
Lucia Languino, PhD (Thomas Jefferson University), Dmitry Gabrilovich, MD, PhD (The Wistar Institute), Maria Caino, PhD (The Wistar Institute)