Molecular underpinnings of systemic treatment resistance in metastatic castration-resistant prostate cancer / [Az áttétes kasztrációrezisztens prosztatarák gyógyszer-rezisztenciájának molekuláris vonatkozásai]

In the last few years, several new drugs with various mechanisms of action have been approved for the treatment of castration-resistant prostate cancer. Due to this development, therapeutic decision-making has become increasingly complex. Therefore, therapy selection as well as timing and sequence of treatments need to be optimized in an individual manner. In addition, also for these novel therapies, baseline and acquired as well as cross-resistance have been observed. Underlying mechanisms become increasingly clear, resulting in a shift from empiric-based towards rational-based therapeutic decision-making. In the present review, we provide an overview on the resistance mechanisms against the most frequently applied systemic treatments of metastatic castration-resistant prostate cancer such as docetaxel, abiraterone and enzalutamide. We summarize - among others - the mechanisms by MDR (multidrug-resistant) protein expression, alterations of androgen receptor, Wnt, p53 and DNA-repair pathways (BRCA/ATM) as well as resistance through therapy-induced neuroendocrine differentiation of the tumour. Orv Hetil. 2020; 161(20): 813-820.

The Achievement of Long-Term CRPC Control in a Patient with Enzalutamide-Induced Nausea and Fatigue after Overcoming the Adverse Events with a Temporary Drug Holiday.

While the overall survival of patients with castration-resistant prostate cancer (CRPC) has been prolonged by enzalutamide, a considerable number of patients suffer from enzalutamide-induced nausea and fatigue. An 86-year-old male patient who started enzalutamide (160 mg) for CRPC treatment, experienced nausea and vomiting approximately 2 weeks after the start of treatment. Enzalutamide treatment was stopped for two weeks, then restarted enzalutamide at a half-dose (80 mg); the dose was then increased to 120 mg. He remained free from any adverse events and showed good CRPC control for 53 months. We herein report the case of a patient with enzalutamide-induced nausea and vomiting, whose symptoms were overcome and in whom long-term CRPC control was achieved following a temporary drug holiday.

Apalutamid: Eine neue Option für die Therapie des Hochrisiko-M0CRPC.

Das Auftreten von Metastasen stellt beim nicht-metastasierten kastrationsresistenten Prostatakarzinom (M0CRPC) einen Wendepunkt in der Erkrankung dar. Apalutamid, ein neuer Androgenrezeptorinhibitor (ARI), verlängerte in der SPARTAN-Studie beim Hochrisiko-M0CRPC im Vergleich zu Placebo das metastasenfreie Überleben (MFS) signifikant. Ähnliches ergab die PROSPER-Studie für Enzalutamid. Internationale Leitlinien empfehlen die beiden Wirkstoffe seit 2018 für die Therapie des Hochrisiko-M0CRPC.

[Androgen receptor-mediated processes in castrate-resistant metastatic prostate cancer]. / Androgénreceptor mediálta folyamatok metasztatikus kasztrációrezisztens prosztatadaganatban.

In the past six years, five new drugs have been approved by the FDA for the treatment of metastatic castrate-resistant prostate cancer. While the disease itself still remains incurable, the sequential use of these drugs can significantly prolong survival while maintaining good quality of life. Research from the past decade made it clear that androgen receptor-mediated processes play a central part in the progression of the disease. Hormonal mechanisms related to androgen-receptors can remain active until late stages of the disease. A deeper understanding of these mechanisms has led to the introduction of new endocrine therapies, which resulted in a change of the nomenclature. The identification and remodelling of androgen receptor mutations that are responsible for primary and secondary resistance developing during the new therapies can pave the way to new and more efficient androgen receptor inhibitor treatments. The aim of the review is to present the pathophysiology of the androgen receptor signaling axis at the receptor level, to review FDA-approved drugs and to draw attention to the most promising developments in the treatment of this disease. Orv. Hetil., 2017, 158(2), 42-49.

[Hormonal treatment in prostate cancer]. / Le traitement hormonal du cancer de la prostate.

AIM: To describe drugs used in the hormonal treatment (hormonotherapy) of prostate cancer. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: LHRH analogs and the antiandrogens remain the cornerstone in the treatment of locally advanced and metastatic prostate cancer. New therapeutic classes emerged recently (inhibitor of the synthesis of the androgen, the new antiandrogens) and allowed to grow again the limits of the hormone resistance and define the concept castration-resistant prostate cancer. CONCLUSION: The hormonal treatment of the prostate cancer grew rich of new therapeutic classes which are going to change the medical care of the prostate cancer in the coming years and the urologist must play its full part.