Related Experiment Video
Updated: Sep 14, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Novel Therapeutic Strategies for Metastatic Prostate Cancer Care
Alessia Cimadamore1, Cristina Boixareu2, Adam Sharp2
1Institute of Pathological Anatomy, Department of Medicine, University of Udine, Udine, Italy.
Background And Objective:
The elucidation of prostate cancer biology and genomics has led to new therapies improving disease outcomes with novel androgen receptor (AR) pathway inhibitors (ARPIs), taxanes, and targeted therapeutics that require disease molecular stratification.
Methods:
We are presenting a narrative and qualitative synthesis based on a systematic search. Medline (PubMed) and Embase (OvidSP) were searched (October 1, 2024, covering 2019-2024) using keywords and Medical Subject Headings terms; ClinicalTrials.gov and ASCO/ESMO abstracts were also reviewed. The inclusion criteria were phase 1-3 studies on molecular targets or therapies for metastatic prostate cancer with posted results. The exclusion criteria included non-English articles, reviews, meta-analyses, commentaries, case reports, duplicates, nonhuman/preclinical studies, protocols, and studies lacking molecular targets.
Key Findings And Limitations:
Targeted therapies have emerged for specific molecular subtypes of advanced prostate cancer. For instance, poly(ADP)-ribose polymerase inhibitors target DNA repair defective prostate cancer (especially BRCA2 and PALB2 biallelic loss). Immune checkpoint inhibitors against PD-1/PD-L1 are effective in hypermutated prostate cancer cases, especially those with mismatch repair defective (MMRd) disease. Additionally, 177Lu-PSMA-617 impacts prostate-specific membrane antigen (folate hydrolase) expressing disease. Several other major therapeutic advances are envisioned in the near future, including targeting novel cell surface proteins with T-cell engager antibody constructs, immunoconjugates, and radiopharmaceuticals. Other rational therapeutic strategies are being pursued, targeting continued AR signalling; AR cofactors, for example, P300; PI3K/AKT signalling; the PRC2 complex protein including EZH2; as well as novel synthetic lethal strategies.
Conclusions And Clinical Implications:
A rapidly evolving standard of care is anticipated for metastatic prostate cancer, making it imperative that rational registration trial designs incorporating multipurpose biomarkers to accelerate anticancer drug development are pursued.
Insights
Advancements in prostate cancer genomics enable targeted therapies like PARP inhibitors and immune checkpoint inhibitors. Personalized treatment strategies are crucial for improving outcomes in metastatic prostate cancer.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Prostate cancer research has significantly advanced, leading to novel therapies.
- Understanding prostate cancer biology and genomics is key to developing new treatments.
Purpose of the Study:
- To synthesize current knowledge on targeted therapies for advanced prostate cancer.
- To review molecular targets and therapeutic advances in prostate cancer treatment.
Main Methods:
- Systematic literature search of Medline, Embase, ClinicalTrials.gov, and conference abstracts.
- Inclusion of phase 1-3 studies on molecular targets or therapies for metastatic prostate cancer.
- Exclusion of non-English articles, reviews, and preclinical studies.
Main Results:
- Targeted therapies are available for specific molecular subtypes, including PARP inhibitors for DNA repair defects and immune checkpoint inhibitors for MMRd disease.
- 177Lu-PSMA-617 is effective for prostate-specific membrane antigen-expressing cancers.
- Future therapies include T-cell engagers, immunoconjugates, radiopharmaceuticals, and agents targeting AR signaling, cofactors, PI3K/AKT, and EZH2.
Conclusions:
- The standard of care for metastatic prostate cancer is rapidly evolving.
- Rational trial designs with multipurpose biomarkers are essential for accelerating drug development.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:27Tumor Immunotherapy
02:56Treatment Resistant Cancers