scholarly journals Changing the History of Prostate Cancer with New Targeted Therapies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 392
Author(s):  
Susana Hernando Polo ◽  
Diana Moreno Muñoz ◽  
Adriana Carolina Rosero Rodríguez ◽  
Jorge Silva Ruiz ◽  
Diana Isabel Rosero Rodríguez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapies ◽  
Synthetic Lethality ◽  
Castration Resistant Prostate Cancer ◽  
Phosphatidylinositol 3 Kinase ◽  
Castration Resistant ◽  
Therapeutic Landscape ◽  
Important Benefit ◽  
History Of ◽  
Repair Genes

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.

Sex Hormones and Prostate Cancer

2020 ◽  
Vol 71 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Richard J. Auchus ◽  
Nima Sharifi
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Current Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
History Of ◽  
Prostate Cancer Research ◽  
Prostate Cancers ◽  
Androgen Independent ◽  
Transition Studies

The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths. Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease. Although it was assumed that the cancer became androgen independent during this transition, studies over the last two decades have shown that these tumors evade treatment via mechanisms that augment acquisition of androgens from circulating precursors, increase sensitivity to androgens and androgen precursors, bypass the androgen receptor, or a combination of these mechanisms. This review summarizes the history of prostate cancer research leading to the contemporary view of androgen dependence for prostate cancers and the current treatment approaches based on this modern paradigm.

scholarly journals Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2034
Author(s):  
Soraia Lobo-Martins ◽  
Arlindo R. Ferreira ◽  
André Mansinho ◽  
Sandra Casimiro ◽  
Kim Leitzel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Unmet Need ◽  
Bone Alkaline Phosphatase ◽  
Multicenter Clinical Trial ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Landscape ◽  
Skeletal Related Events ◽  
The Impact

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.

scholarly journals Incidence of Skeletal-Related Events in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Alison Tse Kawai ◽  
David Martinez ◽  
Catherine W. Saltus ◽  
Zdravko P. Vassilev ◽  
Montse Soriano-Gabarró ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Incidence Rate ◽  
Incidence Rates ◽  
Negative Consequences ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant ◽  
The Us ◽  
History Of ◽  
Skeletal Related Events

Background and Objective. Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased mortality. We estimated incidence rates of first SREs in a cohort of men with CRPC in the Surveillance, Epidemiology, and End Results-Medicare database. Methods. We included men aged ≥ 65 years with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy (other than nonmelanoma skin cancer) and had surgical or medical castration with subsequent second-line systemic therapy, which was used to infer castration resistance. The first occurrence of an SRE (fracture, bone surgery, radiation therapy, or spinal cord compression) in Medicare claims was identified. Incidence rates of SREs were estimated in all eligible person-time and, in secondary analyses, stratified by any use of bone-targeted agents (BTAs) and history of SRE. Results. Of 2,234 men with CRPC (84% white, mean age = 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the incidence rate of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The incidence rate of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any BTA use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. The incidence rate in patients with no history of SRE was 3.33 (95% CI 3.01-3.68) per 100 person-months, and in patients who had such a history, it was 4.20 (95% CI 3.84-4.58) per 100 person-months. Conclusions. In this large cohort of elderly men with CRPC in the US, SREs were common. A decrease in incidence of SREs after starting BTA is suggested, but the magnitude of the effect may be confounded by indication and other factors such as age and prior SRE.

scholarly journals Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline

2020 ◽  
Vol 38 (15) ◽  
pp. 1736-1743 ◽  
Author(s):  
Philip J. Saylor ◽  
R. Bryan Rumble ◽  
Scott Tagawa ◽  
James A. Eastham ◽  
Antonio Finelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapies ◽  
Bone Health ◽  
Cancer Care ◽  
Expert Panel ◽  
Scientific Evidence ◽  
Professional Organizations ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Evidence Based Care

PURPOSE In 2017, Cancer Care Ontario’s Program in Evidence-Based Care released the Bone Health and Bone-Targeted Therapies for Prostate Cancer guideline. This guideline included recommendations across a relatively broad clinical spectrum within prostate cancer. Topics addressed ranged from management of osteoporotic fracture risk in nonmetastatic disease to management of men with castration-resistant prostate cancer metastatic to bone. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS The Bone Health and Bone-Targeted Therapies for Prostate Cancer guideline was reviewed for developmental rigor by methodologists. An ASCO Expert Panel then reviewed the content and the recommendations. RESULTS The ASCO Expert Panel determined that the recommendations from the Bone Health and Bone-Targeted Therapies for Prostate Cancer guideline were clear, thorough, and based on the most relevant scientific evidence. ASCO wholly endorses the Bone Health and Bone-Targeted Therapies for Prostate Cancer guideline. RECOMMENDATIONS The ASCO Expert Panel endorses all the original guideline recommendations as written and offers a series of discussion points to guide practice for clinicians as they manage bone-related risks within this patient population.

Inherited mutations in DNA repair genes in men with metastatic castration-resistant prostate cancer.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5009-5009 ◽  
Author(s):  
Peter Nelson ◽  
Joaquin Mateo ◽  
Himisha Beltran ◽  
Navonil De Sarkar ◽  
Olivier Elemento ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Dna Repair Genes ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Inherited Mutations ◽  
Repair Genes

Castration-Resistant Prostate Cancer: Targeted Therapies

Chemotherapy ◽  
2011 ◽  
Vol 57 (2) ◽  
pp. 115-127 ◽  
Author(s):  
S. Leo ◽  
C. Accettura ◽  
V. Lorusso
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapies ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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