Resistenzmechanismen unter antihormoneller Therapie des fortgeschrittenen Prostatakarzinoms

Abstract

With the development of Abiraterone and Enzalutamide new treatment option have become available in addition to Docetaxel for first-line treatment of castration resistant prostate cancer. However, resistance and ultimately failure occurs inevitably with all available treatment options. Moreover, cross-resistance leads to considerably reduced efficacy in second-line treatment. Preclinical data suggest discriminative mechanisms of resistance development for Abiraterone and Enzalutamide. Clinical confirmation of these putative mechanisms for treatment failure might facilitate recommendations for future sequencing of these drugs.

Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells

“…Resistance to anti-cancer therapies is facilitated through an array of mechanisms that vary across tumor types [63, 64]. In the present study, we demonstrated that RES modulates mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells.…”

Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel

“…RM-581 was significantly more active than all the drugs tested at 1 and 5 µM except for docetaxel tested at 1 µM, which showed slight but significantly higher potency. As a second step, we performed an assay using multiple concentrations from 1 nM to 10 µM to better compare the anticancer potency between RM-581 and docetaxel ( Figure 5 B), a cytotoxic agent established in the last few decades as a gold standard for metastatic CRPC cases [ 8 , 10 , 11 , 17 , 18 ]. In this assay and others, the antiproliferative activity of docetaxel showed an unexpected profile depending on concentration.…”

“…Abiraterone acetate (an inhibitor of androgen biosynthesis) [ 12 ], enzalutamide (a new generation of antiandrogen) [ 13 ], and cabazitaxel (a new generation of taxotere) [ 14 ] are three relevant examples of new drugs obtained from these research efforts that significantly impacted the median survival of CRPC patients [ 15 , 16 ]. However, resistance again occurs, even for those new drugs, leaving these resistant patients with no viable therapeutic options [ 17 , 18 ]. The development of innovative molecules acting by different mechanisms of action are thus urgently needed to give new hope to these doomed PCa patients [ 19 ].…”

Management des metastasierten hormonsensitiven Prostatakarzinoms

“…Ein Grund könnte sein, dass unter Apalutamid plus ADT in der TITAN-Biomarkerpopulation signifikant weniger Androgenrezeptor-Aberrationen als unter alleiniger ADT festgestellt wurden [18]. Denn antihormonelle Therapien können durch Androgenrezeptor-Veränderungen zu Resistenzen führen, die deren Wirksamkeit sowie auch die Wirksamkeit von anderen antihormonellen Therapien als Folgetherapie beeinflussen können [19]. Die Wirksamkeit lässt sich aber weder quantifizieren noch zwischen den einzelnen Folgetherapien differenzieren.…”