Androgen Receptor Gene Pathway Upregulation and Radiation Resistance in Oligometastatic Prostate Cancer

Saxby, Helen; Boussios, Stergios; Mikropoulos, Christos

doi:10.3390/ijms23094786

Cited by 12 publications

(3 citation statements)

References 61 publications

(71 reference statements)

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“…There are several published trials demonstrating a survival advantage with an aggressive approach of local treatments such as salvage prostatectomy, or salvage ultrahypofractionated radiotherapy. There is robust evidence indicating that AR activates DNA repair pathways, which provides a rationale behind the use of ADT with SABR for hormone-sensitive OMPC (12).…”

Section: Rationale and Knowledge Gapmentioning

confidence: 99%

Prostate cancer—what about oligometastatic disease and stereotactic ablative radiotherapy?—a narrative review

Mikropoulos¹,

Saxby²,

Boussios³

2023

Ann Palliat Med

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Background and Objective: Oligometastatic prostate cancer (OMPC) encompasses a heterogenous group of clinical entities defined by the timing of the development of metastases. These include de novo oligometastatic, oligorecurrent and oligoprogressive prostate cancer (PrCa). We describe the evidence supporting the use of stereotactic ablative radiotherapy (SABR) to the oligometastases to improve patient outcomes in each of these settings.Methods: Published clinical trials relevant to 'OMPC' and 'SABR' where used for this narrative review.

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Section: Rationale and Knowledge Gapmentioning

confidence: 99%

Prostate cancer—what about oligometastatic disease and stereotactic ablative radiotherapy?—a narrative review

Mikropoulos¹,

Saxby²,

Boussios³

2023

Ann Palliat Med

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“…Until 2010, patients with metastatic castration-resistant prostate cancer have been treated with chemotherapy, which can be combined with androgen deprivation therapy (ADT). The addition of ADT to localised prostate radiotherapy improves survival as it sensitises prostate cancer to radiotherapy-induced cell death [ 126 ]. Technological advancements in the past two decades revealed that residual androgens, ADT-induced AR splice variants, and AR mutations are common mechanisms of metastatic castration-resistant prostate cancer.…”

Section: Parp Inhibitors Development Across Tumour Typesmentioning

confidence: 99%

BRCA Mutations in Ovarian and Prostate Cancer: Bench to Bedside

Boussios

Rassy

Moschetta

et al. 2022

Cancers

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DNA damage repair (DDR) defects are common in different cancer types, and these alterations can be exploited therapeutically. Epithelial ovarian cancer (EOC) is among the tumours with the highest percentage of hereditary cases. BRCA1 and BRCA2 predisposing pathogenic variants (PVs) were the first to be associated with EOC, whereas additional genes comprising the homologous recombination (HR) pathway have been discovered with DNA sequencing technologies. The incidence of DDR alterations among patients with metastatic prostate cancer is much higher compared to those with localized disease. Genetic testing is playing an increasingly important role in the treatment of patients with ovarian and prostate cancer. The development of poly (ADP-ribose) polymerase (PARP) inhibitors offers a therapeutic strategy for patients with EOC. One of the mechanisms of PARP inhibitors exploits the concept of synthetic lethality. Tumours with BRCA1 or BRCA2 mutations are highly sensitive to PARP inhibitors. Moreover, the synthetic lethal interaction may be exploited beyond germline BRCA mutations in the context of HR deficiency, and this is an area of ongoing research. PARP inhibitors are in advanced stages of development as a treatment for metastatic castration-resistant prostate cancer. However, there is a major concern regarding the need to identify reliable biomarkers predictive of treatment response. In this review, we explore the mechanisms of DDR, the potential for genomic analysis of ovarian and prostate cancer, and therapeutics of PARP inhibitors, along with predictive biomarkers.

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“…There is robust evidence indicating that androgen receptors activate DNA repair pathways, which provides a rationale behind the use of ADT with SABR for hormone-sensitive prostate oligo-metastases. Chronic inflammation, often linked to prostatitis-induced cellular and genetic damage, strongly influences prostate cancer development and progression [6,7] .…”

Section: Introductionmentioning

confidence: 99%

New approaches and prospects of immunotherapy and gene therapy for prostate cancer

Bibi,

Sarkar

2024

J Transl Genet Genom

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Prostate cancer stands as the most prevalent cancer globally, constituting 21% of all cancer diagnoses in male patients. Urgent optimization of prostate cancer care is essential, given that this disease claims 345,000 lives every year. These innovative approaches hold substantial promise for both researchers and patients, representing a beacon of hope in the inhibitory act against prostate cancer. Prostate cancer's gradual advancement deems it suitable for immune therapy, but trials in metastatic cases show limited effectiveness, likely due to compromised immunity. Hindered by defective cellular responses, an immune-suppressive microenvironment, emerging evidence and breakthroughs, such as CAR-T therapy, inspire cautious optimism for advanced prostate cancer immunotherapy. Tumors utilize tactics to escape immune recognition, promoting the proliferation of MDSCs, Treg cells, and TAMs. Immunotherapy targets prostate cancer by mostly expressed target proteins and overexpressed target proteins. Immune cells play a role in tumor development and metastasis in advanced prostate cancer. Modulating the tumor microenvironment presents therapeutic possibilities. Certain prostate cancer types exhibit potential responses to immune checkpoint inhibitors, yet obstacles remain, necessitating additional research for enhanced efficacy. Immunotherapy faces hurdles in prostate cancer—limited inflammation, scarce antigens, and a resistant microenvironment. Grasping resistance intricacies is pivotal. The identification of DNA's helical structure propelled global progress in disease treatment through gene therapy. Choosing gene therapy vectors is critical; viruses are potent but toxic, while nonviral options, though less toxic, encounter barriers affecting transfection. In the realm of prostate cancer treatment, immunotherapy and gene therapy are emerging as increasingly viable options.

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Androgen Receptor Gene Pathway Upregulation and Radiation Resistance in Oligometastatic Prostate Cancer

Cited by 12 publications

References 61 publications

Prostate cancer—what about oligometastatic disease and stereotactic ablative radiotherapy?—a narrative review

Prostate cancer—what about oligometastatic disease and stereotactic ablative radiotherapy?—a narrative review

BRCA Mutations in Ovarian and Prostate Cancer: Bench to Bedside

New approaches and prospects of immunotherapy and gene therapy for prostate cancer

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