The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) is changing due to the emergence of new targeted therapies for the treatment of different molecular subtypes. Some biomarkers are described as potential molecular targets different from classic androgen receptors (AR). Approximately 20–25% of mCRPCs have somatic or germline alterations in DNA repair genes involved in homologous recombination. These subtypes are usually associated with more aggressive disease. Inhibitors of the enzyme poly ADP ribose polymerase (PARPi) have demonstrated an important benefit in the treatment of these subtypes of tumors. However, tumors that resistant to PARPi and wildtype BRCA tumors do not benefit from these therapies. Recent studies are exploring drug combinations with phosphatidylinositol-3-kinase (PI3K) or protein kinase B (AKT) inhibitors, as mechanisms to overcome resistance or to induce BRCAness and synthetic lethality. This article reviews various different novel strategies to improve outcomes in patients with prostate cancer.

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The advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to immunotherapy represents one of the current challenges in this clinical scenario. The management of advanced castration-resistant prostate cancer is rapidly evolving and immunotherapy treatments, mostly consisting of immune checkpoint inhibitors combinations, BiTE® (bispecific T-cell engager) immune therapies, and chimeric antigen receptors (CAR) are in development with promising results. This review analyses the current evidence of immunotherapy treatments for mCRPC, evaluating past failures and promising approaches and discussing the directions for future research.

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16027 Background: As a result of the improvement in oncological treatments, MPCA could arise as a more frequent problem in Public Health. The purpose of this retrospective review was to estimate both the incidence and medical features of MPCA pts treated at the Instituto Oncológico Henry Moore (IOHM). Methods: We analyzed 17,100 medical charts from our database since 1987 and identified 378 MPC (2,21%). Then we retrieved data over the last eight years (1997–2005). Those pts with at least two second primary tumors were included in this analysis. They were categorized as synchronous (second tumor diagnosis within the first six months from the first one) and metachronous (all the remaining). Pts with skin cancer different from melanoma were excluded. Results: One hundred and seventy eight (M:73; F:105) out of 8,500 cancer pts (2.09%) had at least two primary cancers. Median age was 59, 64 and 68 yo at the moment of the first, second and third diagnosis, respectively. In 138 (78%) pts, the diagnosis of the second cancer was suspected by clinical findings, while in 40 (22%) pts, it was discovered because of medical screening in an otherwise asymptomatic pt. (See Table below) The most frequent site combination was breast-breast (n = 21). A total of 57 pts (32%) had a family history of oncologic diseases. With a median follow-up of 31 mo (range: 0,57–311) after the second cancer diagnosis, 127 pts are still alive (71,35%) and 51 (28,65%) are dead. Conclusions: In the last eight years, 178 (2.09%) pts had developed MPC, being breast, prostate, colon and lung the most frequent (first and later) localizations, and breast-breast the most frequent site combination. The so-called “screening effect” seems to have a low impact on the studied population. [Table: see text] No significant financial relationships to disclose.