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2021 Eric Vacca-PCF Young Investigator Award

The αvβ3 Integrin as Therapeutic Target in Neuroendocrine Prostate Cancer

Fabio Quaglia, PhD
Thomas Jefferson University

Mentors: Lucia Languino, PhD, William Kelly, DO

Description:

  • Neuroendocrine prostate cancer (NEPC) is an aggressive and treatment-resistant form of castration resistant prostate cancer (CRPC), which has lost features of prostate adenocarcinoma cells and gained features of neuroendocrine cells.
  • Dr. Fabio Quaglia and colleagues have identified αVβ3 integrin as a promising therapeutic target for NEPC. αVβ3 integrin is highly expressed in NEPC, while absent in prostate adenocarcinoma. In contrast, the related integrin family member αVβ6 shows an opposite pattern of expression with high levels in prostate adenocarcinoma and low levels in NEPC.
  • In this study, Dr. Quaglia will investigate the mechanisms by which αVβ3 contributes to the NEPC phenotype and validate its potential as a therapeutic target.
  • The expression of αVβ3 integrin, αVβ6 integrin, and αVβ3 integrin downstream effectors during prostate cancer progression toward the NEPC phenotype will be evaluated. Whether any features correlate with clinical outcomes will be determined.
  • To determine the potential therapeutic impact of targeting αVβ3, pharmacologic inhibition and genetic deletion of αVβ3 will be tested in preclinical prostate cancer models.
  • If successful, this project will define the biology of αVβ3 integrin in NEPC and determine its potential as a biomarker and therapeutic target.

What this means to patients: Neuroendocrine prostate cancer (NEPC) is a highly aggressive form of advanced prostate cancer for which new treatments are urgently needed. Dr. Quaglia will determine whether αVβ3 integrin may be a promising new treatment target and biomarker for NEPC, as well as the biology by which αVβ3 integrin contributes to this phenotype.