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Bone microenvironment signaling of cancer stem cells as a therapeutic target in metastatic prostate cancer

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Abstract

Prostate cancer (PCa) is one of the most prevalent cancers and the second leading cause of cancer death among US males. When diagnosed in an early disease stage, primary tumors of PCa may be treated with surgical resection or radiation, sometimes combined with androgen deprivation therapy, with favorable outcomes. Unfortunately, the treatment efficacy of each approach decreases significantly in later stages of PCa that involve metastasis to soft tissues and bone. Metastatic PCa is a heterogeneous disease containing host cells, mature cancer cells, and subpopulation of cancer stem cells (CSC). CSCs are highly tumorigenic due to their self-renewing and differentiating potential, clinically resulting in recurrence and resistance to standard therapies. Therefore, there is a large unmet clinical need to develop therapies, which target CSC activity. In this review, we summarize the main signaling pathways that are implicated in the current pre-clinical and clinical studies of recurrent metastatic PCa within the bone microenvironment targeting CSCs and discuss the trajectory of therapeutics moving forward.

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Acknowledgments

Dr. Younghun Jung gave valuable critique on the signaling pathway of cancer stem cells. R.T. receives support as the Major McKinley Ash Collegiate Professor.

Funding

This work is financially supported by the National Cancer Institute (R.S. Taichman (CA093900 and CA163124)), the Department of Defense (R.S. Taichman (W81XW-15-1-0413 and W81XWH-14-1-0403)) and the Prostate Cancer Foundation Challenge Award R.S. Taichman (16CHAL05), Prostate Cancer Foundation Challenge Award (F.C. Cackowski (16CHAL05), a Career Enhancement Award, Sub-Award (F.C. Cackowski ((F048931)) of NIH/NCI Prostate Cancer Specialized Program in Research Excellence (SPORE) to Arul Chinnaiyan at the University of Michigan (F036250), and Prostate Cancer Foundation Young Investigator Award (F.C. Cackowski (18YOUN04).

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Lee, C.H., Decker, A.M., Cackowski, F.C. et al. Bone microenvironment signaling of cancer stem cells as a therapeutic target in metastatic prostate cancer. Cell Biol Toxicol 36, 115–130 (2020). https://doi.org/10.1007/s10565-019-09483-7

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