New Strategies Against Prostate Cancer – Pt(II)-Based Chemotherapy

Abstract

Prostate cancer is the second most common cancer worldwide and the sixth cause of cancer-related death in men. When hormone therapy fails to control tumour growth, castration-resistant prostate cancer (CRPC) occurs and chemotherapy drugs must be administered. Since 2004, docetaxel administration is the standard of care in metastatic CRPC, although it presents severe limitations such as acquired resistance and poor prognosis. An analogue (cabazitaxel) was approved by the FDA in 2010 as a second-line chemotherapeutic agent. Novel immuno-and hormonal therapy agents, as well as tumour vaccines, have been recently developed, but new strategies are still needed for effectively handling this type of neoplasia. Platinum compounds, in particular, have been the object of a growing interest, despite the former belief that they should have modest activity against prostate cancer. Compounds such as carboplatin, oxaliplatin or satraplatin, either alone or in combination, have lately shown promising results. In order to overcome the deleterious side-effects usually associated to these metal-based agents, several approaches have been followed with a view to optimise drug delivery and targeting, some of which showed considerable success in CRPC. Platinum drugs may therefore have an important role in the chemotherapeutic management of human metastatic castration-resistant prostate cancer, mostly in second-line strategies. The present review addresses the most relevant studies on platinum-based antineoplastic agents towards CRPC in the last decade -from first-and second-generation complexes to newly developed compounds.

Effects of tumor-suppressor lysyl oxidase propeptide on prostate cancer xenograft growth and its direct interactions with DNA repair pathways

“…Biologic chemotherapeutics which inhibit a single specific pathway and are effective in the short term are often not effective to treat cancer in the long term due to development of drug resistance and robust relapse ( 26 – 29 ). Up-regulation of DNA repair pathways is one way in which tumor cells become resistant to therapy and through which mitotic catastrophe is avoided in damaged tumor cells ( 14 ).…”

Chemotherapy in Prostate Cancer

“…The largest of these studies found a PSA response rate of 34.5 % in 80 patients given 50 mg/m 2 of oral cyclophosphamide daily with a mediation response duration of 7.5 months. Carboplatin at 150 mg/m 2 weekly was evaluated in 27 patients with minimal effects (26.9 % of patients had a PSA that declined, but none of the response were >50 % decline) [65]. A study in the early 1990s in 25 patients demonstrated a 17 % partial response rate in evaluable patients and a 20 % PSA response rate [66].…”

Cisplatin in combination with programmed cell death protein 5 increases antitumor activity in prostate cancer cells by promoting apoptosis

“…Chemotherapy is one of the primary treatment methods used in prostate cancer patients (7)(8)(9). Cisplatin (chemical structure shown in Fig.…”