Metabolic Imaging of Prostate Cancer Reveals Intrapatient Intermetastasis Response Heterogeneity to Systemic Therapy

Abstract

Systemic therapies can lead to heterogeneous responses in individual metastases of prostate cancer in a patient. Molecular imaging may be useful for identifying heterogeneity and could allow targeted biopsy for molecular analysis or therapy.

Concise Review: Prostate Cancer Stem Cells: Current Understanding

“…Yes (luminal cells) [3,60] No [3] or low [232] PSA+ or PSA- [230,231,233] PSA+ or PSA- [234] No data Phenotype Luminal or basal epithelial cells [229] Luminal or basal epithelial cells [3,32,61,62,79,115,219,235,236] Epithelial or Mesenchymal (EMT) [163,222,225,233,237,238] Epithelial [234], Mesenchymal (EMT) [163], Hematopoietic [234,239] No data Tumorigenicity Upon de-differentiation [14,232] Yes [3,32,61,62,79,115,219,235,236] Probably [240] Probably [241,242] Yes [243,244] Metabolism Primary PC: OXPHOS CRPC: glycolysis (Warburg effect) [26,42] Glycolysis [96] or/and OXPHOS <...>…”

“…Yes [246] Yes [3,32,61,62,115,219,235,236] Yes [222,224,225,230,233,247] Yes [226,228,234] Yes [243,244] Cellular state…”

“…Yes [244,251] Yes [251] Yes, reflection of tumor evolution [160,161,252] Yes (159,135,(151)(152)(153) Yes [243,244,253] ©AlphaMed Press 2018 STEM CELLS example: (a) to predict tumor development; (b) to identify patients with a poor prognosis who can potentially benefit from therapy intensification; (c) to visualize the most critical intratumoral areas containing CSCs that should be taken into account for the local therapy planning (surgery, radiotherapy); (d) to monitor an efficacy of therapeutic approaches administered in cancer patients; (e) to diagnose local or distant tumor recurrences after therapy; and (f ) to develop novel specific anti-CSC therapeutics to effectively destroy the most aggressive and treatment-resistant CSCs. Although a number of strategies for PCSC enrichment and analysis are considered in this review article, there are no specific PCSC markers known up to date which are already implemented in clinical practices.…”

Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer cells

“…Although the initial response to treatment is high, after ~18 months there is a state of resistance to androgens, termed castration-resistant PC (CRPC) (7), which is associated in up to 40% of cases with metastasis and heterogeneity in the intra patient intermetastasis therapeutic response. The expected survival rate for patients with PC is ~18%, but when recurrences appear it decreases to 5-10% (8). Treatment options for CRPC and metastatic CRPC (mCRPC) include docetaxel (DOCE)-based regimens (9) alone or in association with, for example, ADT (10)(11)(12)(13) or anti-angiogenic (bevacizumab), anti-proliferative and anti-migratory (tyrosine kinase inhibitors) drugs (14,15).…”

Performance of 18F-fluciclovine PET/MR in the evaluation of osseous metastases from castration-resistant prostate cancer

“…All patients were receiving androgen deprivation therapy with a GnRH agonist at the time of imaging, and although all were considered to be castrate-resistant and being considered for radium-223 therapy, it is not possible to determine if some metastases that were visible on MRI had been previously rendered metabolically quiescent and inactive (i.e. 18 F-fluciclovine-negative), given that heterogeneity of response between skeletal metastases may exist [7]. There was no metabolic comparator in this study and the standard of reference only relied on osteoblastic or morphologic criteria (BS/CT/MRI).…”