Summarizing the resistance mechanisms

Mechanism of therapy resistanceDescriptionKey findingsReferences
Docetaxel resistanceIncludes irregular control of molecules involved in cell survival and death.
Upregulation of GATA2 increases IGF2 resulting in docetaxel resistance.
Overexpression of certain cytokines including interleukin (IL)-6, IL-8, TGF-β1, CCL2, and MIC-1 promotes the growth and prevent cell death.
AR-V7 has shown sensitivity to the microtubule stabilization caused by taxanes thus contributing resistance.		Genes associated in resistance are: HSP, STAT1, NF-κB, STAT3 and clusterin.
Decreased p53 activity is associated with a lack of response to docetaxel.
Higher expression of class IV β-tubulin and mutations in class 1 β-tubulin, has lead to impaired polymerization in cells resistant to docetaxel.		[62–64, 21, 68]
Cabazitaxel resistanceChemotherapeutic.
Overexpression of ETS related gene (ERG) in prostate cells causes resistance to cabazitaxel.
Tumors lacking retinoblastoma exhibit a more favourable response to cabazitaxel.		ERG interaction interruption restores sensitivity.[72, 73]
Abiraterone resistanceRe-activation of androgen synthesis in PC is accompanying with resistance to abiraterone in patients.
Steroidogenesis: upregulation of steroidal hormones by IL-6.		Enzymes involved in steroidogenesis are AKR1C3, HSD3B2, and AKR1C3.
Glucocorticoids minimizes the adverse effects linked to abiraterone treatment and can stimulate AR and trigger androgen independent cell growth.		[76, 77]
Enzalutamide resistanceResistance in cells is linked to changes in steroidogenesis, glucose metabolism, and autophagy.
Genes related to steroid biosynthesis show increased expression, with AKR1C3.
Overexpression of p52 leads to enzalutamide resistance, caused by alterations in glucose metabolism and the expression of AR splice variants.		Exhibits an increase in the levels of androgen and its precursors, such as cholesterol, DHEA, and progesterone.
AR mutations in the ligand binding domain affecting around 10–30% of CRPC patients.
Overexpression of IL-6 leads to constitutive STAT3 activation, as a result enzalutamide becomes ineffective.		[78, 79, 81, 82]
Cross resistanceLower likelihood of cross-resistance between cabazitaxel and AR-targeted therapies compared to docetaxel.Prior treatment with abiraterone or docetaxel may experience a decreased response to subsequent enzalutamide treatment, resulting in diminished PSA decline and progression-free survival.[83–85]

PSA: prostate-specific antigen; ERG: ETS-related gene; AR-V7: androgen receptor splice variant 7