The Role of Lineage Plasticity in Prostate Cancer Therapy Resistance.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Himisha BeltranPeter S Nelson

Abstract

Lineage plasticity has emerged as an important mechanism of treatment resistance in prostate cancer. Treatment-refractory prostate cancers are increasingly associated with loss of luminal prostate markers, and in many cases induction of developmental programs, stem cell-like phenotypes, and neuroendocrine/neuronal features. Clinically, lineage plasticity may manifest as low PSA progression, resistance to androgen receptor (AR) pathway inhibitors, and sometimes small cell/neuroendocrine pathologic features observed on metastatic biopsy. This mechanism is not restricted to prostate cancer as other malignancies also demonstrate lineage plasticity during resistance to targeted therapies. At present, there is no established therapeutic approach for patients with advanced prostate cancer developing lineage plasticity or small cell neuroendocrine prostate cancer (NEPC) due to knowledge gaps in the underlying biology. Few clinical trials address questions in this space, and the outlook for patients remains poor. To move forward, urgently needed are: (i) a fundamental understanding of how lineage plasticity occurs and how it can best be defined; (ii) the temporal contribution and cooperation of emerging drivers; (iii) preclinical models...Continue Reading

Citations

Mar 15, 2020·Stem Cells Translational Medicine·Anastasia C HepburnRakesh Heer
Oct 9, 2019·Nature Reviews. Urology·Sheng-Yu KuHimisha Beltran
May 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Joshi J AlumkalZheng Xia
Feb 6, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amy C Mandigo, Karen E Knudsen
Oct 8, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fatima KarzaiWilliam L Dahut
Nov 18, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Diana C DeLuciaJohn K Lee
Nov 11, 2020·International Journal of Molecular Sciences·Anh-Tien TonArtem Cherkasov
Jun 5, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matti AnnalaAlexander W Wyatt
Jun 20, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dae-Hwan KimJoshi J Alumkal

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