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Updated: Nov 8, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Drug and molecular radiotherapy combinations for metastatic castration resistant prostate cancer
Magdalena Staniszewska1, Janette Iking1, Katharina Lückerath2
1Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.
Abstract:
Metastatic castration resistant prostate cancer (mCRPC) is a highly lethal disease. Several novel therapies have been assessed in the past years. Targeting DNA damage response (DDR) pathways in prostate cancer became a promising treatment strategy and olaparib and rucaparib, Poly(ADP-ribose) polymerase (PARP) inhibitors, have been approved for patients carrying mutations in homologous recombination (HR) repair pathways. Other DDR inhibitor targets, such as ATM, ATR, CHK1, CHK2, and WEE1 are under extensive investigation. Additionally, molecular radiotherapy (MRT) including [177Lu]Lu-PSMA, [225Ac]Ac-PSMA, [223Ra]Ra-dichloride, [153Sm]-EDTMP, [188Re]Re-HDMP and GRPR-targeted MRT treat cancer through internal ionizing radiation causing DNA damage and demonstrate promising efficacy in clinical trials. In the field of immunotherapy, checkpoint inhibition as well as sipuleucel-T and PROSTVAC demonstrated only limited efficacy in mCRPC when used as monotherapy. This review discusses recent therapeutic strategies for mCRPC highlighting the need for rational combination of treatment options.
Insights
Novel therapies for metastatic castration-resistant prostate cancer (mCRPC) target DNA damage response (DDR) pathways and utilize molecular radiotherapy (MRT). Combinations of these advanced treatments show promise for improving outcomes in mCRPC patients.
Area of Science:
- Oncology
- Medical Physics
- Pharmacology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) is a lethal malignancy with limited treatment options.
- Targeting DNA damage response (DDR) pathways has emerged as a promising therapeutic strategy.
- Recent advancements include PARP inhibitors and molecular radiotherapy (MRT).
Purpose of the Study:
- To review recent therapeutic strategies for mCRPC.
- To highlight the potential of combining novel treatment modalities.
- To discuss the role of DDR inhibitors and MRT in mCRPC management.
Main Methods:
- Literature review of recent clinical trials and research on mCRPC therapies.
- Analysis of novel treatment strategies including Poly(ADP-ribose) polymerase (PARP) inhibitors and molecular radiotherapy (MRT).
- Evaluation of immunotherapy approaches and their efficacy in mCRPC.
Main Results:
- Poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib) are approved for HR-deficient mCRPC.
- Various molecular radiotherapy (MRT) agents ([177Lu]Lu-PSMA, [225Ac]Ac-PSMA, [223Ra]Ra-dichloride, etc.) show promising efficacy.
- Immunotherapy has demonstrated limited efficacy as monotherapy in mCRPC.
Conclusions:
- Targeting DNA damage response (DDR) pathways represents a significant advancement in mCRPC treatment.
- Molecular radiotherapy (MRT) offers a novel approach to internal radiation therapy for mCRPC.
- Rational combination of existing and novel therapies is crucial for optimizing mCRPC treatment outcomes.
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