Extracellular Vesicle-Mediated Reversal of Paclitaxel Resistance in Prostate Cancer.
Prostate cancer (PCa) is the most common solid tumor in males and the second leading cause of cancer-related deaths in males in the United States. The current first line therapy for metastatic PCa is androgen deprivation therapy and is initially effective against the disease. However, castrate resistant prostate cancer (CRPC) develops in many men within 18-36 months, rendering this treatment ineffective. Chemotherapy, with a class of drugs known as taxanes is the standard-of-care cytotoxic option in metastatic castrate resistant PCa (mCRPC). However, the overall survival advantage for chemotherapy in mCRPC is only 2.2 months and the cancer cells often become resistant to these drugs as well. Once patients fail chemotherapy the progression to death is inevitable. Extracellular vesicles (EVs) are involved in cell signaling and play a role in cancer progression. Previous work has demonstrated that EVs are involved in the development of drug resistance in cancer cells. We report the reversal of taxane resistance and tumorigenic phenotype in PCa cells after EVs treatment. This study suggests that EVs represent a potentially novel therapeutic treatment option for CRPC.
Department of Medicine, Rhode Island Hospital, Providence, RI.
Justin Q
JQ
Wang
Department of Medicine, Rhode Island Hospital, Providence, RI.
Austin
A
DeChalus
Department of Medicine, Rhode Island Hospital, Providence, RI.
Devin N
DN
Chatterjee
Department of Urology, School of Medicine, University of Michigan, 1500 E. Medical Center Dr., Room 5308 CCGCB, Ann Arbor, MI 48105, USA; Center for Translational Medicine, Guangxi Medical University, Nanning, China.
Evan T
ET
Keller
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
Atsushi
A
Mizokami
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Giovanni
G
Camussi
Regenerative Sciences Institute, 1230 Bordeaux Dr., Sunnyvale, CA.
Andrew R
AR
Mendelsohn
Department of Urology, Miriam Hospital, The Alpert Medical School of Brown University, Providence, RI.
Joseph F
JF
Renzulli Ii
Department of Medicine, Rhode Island Hospital, Providence, RI.
Peter J
PJ
Quesenberry
Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, Rhode Island.
Devasis
D
Chatterjee
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000067128:Extracellular Vesicles; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction; D043823:Taxoids / Q000627:therapeutic use
D000970:Antineoplastic Agents; D043823:Taxoids; D017239:Paclitaxel