title: Strategies to avoid treatment-induced lineage crisis in advanced prostate cancer.
abstract: The increasing potency of therapies that target the androgen receptor (AR) signalling axis has correlated with a rise in the proportion of patients with prostate cancer harbouring an adaptive phenotype, termed treatment-induced lineage crisis. This phenotype is characterized by features that include soft-tissue metastasis and/or resistance to standard anticancer therapies. Potent anticancer treatments might force cancer cells to evolve and develop alternative cell lineages that are resistant to primary therapies, a mechanism similar to the generation of multidrug- resistant microorganisms after continued antibiotic use. Herein, we assess the hypothesis that treatment-adapted phenotypes harbour reduced AR expression and/or activity, and acquire compensatory strategies for cell survival. We highlight the striking similarities between castration-resistant prostate cancer and triple-negative breast cancer, another poorly differentiated endocrine malignancy. Alternative treatment paradigms are needed to avoid therapy-induced resistance. Herein, we present a new clinical trial strategy designed to evaluate the potential of rapid drug cycling as an approach to delay the onset of resistance and treatment-induced lineage crisis in patients with metastatic castration-resistant prostate cancer.
authors.affiliation: Department of Medical Oncology, Institut Bergonié, 229 Cours de l'Argonne, Bordeaux 33076, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Roubaud
authors.affiliation: Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, 1470 Madison Avenue, New York, New York 10029, USA.
authors.forename: Bobby C
authors.initials: BC
authors.lastname: Liaw
authors.affiliation: Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, 1470 Madison Avenue, New York, New York 10029, USA.
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.affiliation: Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, 1470 Madison Avenue, New York, New York 10029, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mulholland
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D011944:Receptors, Androgen