Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

Abstract

AbstractOver the last few decades, the incidence of urogenital cancers has exhibited diverse trends influenced by screening programs and geographical variations. Among women, there has been a consistent or even increased occurrence of endometrial and ovarian cancers; conversely, prostate cancer remains one of the most diagnosed malignancies, with a rise in reported cases, partly due to enhanced and improved screening efforts.Simultaneously, the landscape of cancer therapeutics has undergone a remarkable evolution, encompassing the introduction of targeted therapies and significant advancements in traditional chemotherapy. Modern targeted treatments aim to selectively address the molecular aberrations driving cancer, minimizing adverse effects on normal cells. However, traditional chemotherapy retains its crucial role, offering a broad-spectrum approach that, despite its wider range of side effects, remains indispensable in the treatment of various cancers, often working synergistically with targeted therapies to enhance overall efficacy.For urogenital cancers, especially ovarian and prostate cancers, DNA damage response inhibitors, such as PARP inhibitors, have emerged as promising therapeutic avenues. In BRCA-mutated ovarian cancer, PARP inhibitors like olaparib and niraparib have demonstrated efficacy, leading to their approval for specific indications. Similarly, patients with DNA damage response mutations have shown sensitivity to these agents in prostate cancer, heralding a new frontier in disease management. Furthermore, the progression of ovarian and prostate cancer is intricately linked to hormonal regulation. Ovarian cancer development has also been associated with prolonged exposure to estrogen, while testosterone and its metabolite dihydrotestosterone, can fuel the growth of prostate cancer cells. Thus, understanding the interplay between hormones, DNA damage and repair mechanisms can hold promise for exploring novel targeted therapies for ovarian and prostate tumors.In addition, it is of primary importance the use of preclinical models that mirror as close as possible the biological and genetic features of patients’ tumors in order to effectively translate novel therapeutic findings “from the bench to the bedside”.In summary, the complex landscape of urogenital cancers underscores the need for innovative approaches. Targeted therapy tailored to DNA repair mechanisms and hormone regulation might offer promising avenues for improving the management and outcomes for patients affected by ovarian and prostate cancers.