Skip to main content
. 2022 Mar 28;23(5):351. doi: 10.3892/etm.2022.11278

Table I.

Factors that maintain tumor indolence and mechanisms mediating a switch into aggressive disease.

Indolence factor First author, year Escape mechanism/aggressiveness induction (Refs.)
Low mutation rate Taylor et al, 2010 Additional genetic aberrations (30)
  Bonollo et al, 2020 CAF effects (88)
  Aggarwal et al, 2018 Epigenetic modifications (50)
Slow proliferation Taylor et al, 2010 Additional genetic aberrations (30)
  Bonollo et al, 2020 CAF effects (88)
  Sugiura et al, 2021 Cell cycle gene hypermethylation (43)
  Sejda et al, 2020 Neurotrophic signaling (98)
Androgen dependence Taylor et al, 2010; Additional genetic aberrations (30,37)
  Beltran et al, 2016    
  Blom et al, 2019 TME factors (89)
  Ngollo et al, 2014; Epigenetic adaptation (40,59)
  Fu et al, 2006    
Nutrient scarcity/hypoxia West et al, 2001 VEGF upregulation (129)
  Ngollo et al, 2014; Epigenetic adaptation (40,48)
  Ge et al, 2020    
  Taylor et al, 2010; Additional genetic aberrations (30,37)
  Beltran et al, 2016    
  Bonollo et al, 2020 Crosstalk with CAFs (88)
Immunosurveillance Ness et al, 2014 Dysfunctional TILs (71)
  Nardone et al, 2016 High regulatory Foxp3+ (75)
  Mariathasan et al, 2018 High M2 macrophages (77)
  Heninger et al, 2016 MHC Class 1 silencing (78)
Fibroblast/stromal-induced inhibition of tumor growth Blom et al, 2019 CAFs activity/epigenetic changes in CAFs (89)
  Bonollo et al, 2020 Increased stromal stiffness (88)
  Sejda et al, 2020 Perineural invasion (98)
  March et al, 2021 Neurotrophic growth factors (99)
Senescence phenotype Ewald et al, 2010 Treatment resistance/therapy escape (110)
  Wang et al, 2020 Secretome sends tumorigenic signals to neighboring cells (108)
Low visceral tropism Beltran et al, 2016 Additional mutations/CNA in critical genes (37)
  Davies et al, 2020 Neuroendocrine differentiation (51)
  Yegnasubramanian et al, 2008 Epigenetic adaptation (49)
Dormancy induction Recasens et al, 2019 Additional genetic aberrations (148)
  Decker et al, 2017 Beta-adrenergic signaling (149)
  Cackowski et al, 2017 TYRO3, MERTK activity (145)

There are several factors that contribute to an indolent phenotype in subsets of prostate cancers. They include inherent properties of a tumor (such as slow proliferation rate, low visceral tropism), effects of treatment, immunosurveillance, TME-related effects, induction of dormancy/quiescence/senescence phenotype. However, as genetic and epigenetic alterations continue to accumulate, combined with the TME-endothelial compartment crosstalk, many tumors eventually escape dormancy and switch to aggressive disease.