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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1

En-Chi Hsu1,2, Meghan A Rice1,2, Abel Bermudez1,2

  • 1Department of Radiology, Stanford University, Stanford, CA 94304.

Proceedings of the National Academy of Sciences of the United States of America
|January 15, 2020
PubMed

Insights

High Trop2 levels drive aggressive prostate cancer growth and metastasis. Targeting Trop2 and PARP1 shows promise for treating castration-resistant and neuroendocrine prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) with metastasis is a leading cause of cancer death in men.
  • Neuroendocrine prostate cancer (NEPC), an aggressive CRPC variant, is increasing due to secondary hormonal therapies.

Purpose of the Study:

  • To investigate the role of Trop2 in prostate cancer progression, metastasis, and neuroendocrine differentiation.
  • To evaluate Trop2 as a therapeutic target in advanced prostate cancer.

Main Methods:

  • Analysis of Trop2 expression in localized prostate cancer, CRPC, and NEPC.
  • In vivo studies using genetic manipulation of Trop2 to assess its impact on tumor growth and metastasis.
  • Investigating the relationship between Trop2, PARP1, and NEPC phenotype.
  • Testing the efficacy of PARP inhibitors in Trop2-driven NEPC models.

Main Results:

  • High Trop2 levels predict recurrence in localized prostate cancer and are elevated in CRPC and NEPC.
  • Trop2 overexpression drives tumor growth and metastasis; Trop2 loss suppresses these.
  • Trop2-driven NEPC exhibits increased PARP1 expression.
  • PARP inhibitors significantly delay tumor growth, metastasis, and reverse neuroendocrine features in Trop2-driven NEPC.

Conclusions:

  • Trop2 is a key driver of prostate cancer growth, metastasis, and neuroendocrine phenotype.
  • Trop2 is a viable therapeutic target for metastatic prostate cancer, particularly NEPC.
  • High Trop2 expression may identify patients who could benefit from Trop2-targeting therapies and PARP1 inhibition.
Keywords:
NEPCTrop2cancerprostate

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