Ionizing Radiation Combined with PARP1 Inhibitor Reduces Radioresistance in Prostate Cancer with RB1/TP53 Loss

Fan, Yu; Fan, Hui; Quan, Zhen; Wu, Xiaohou

doi:10.1080/07357907.2021.1899200

Cited by 6 publications

(6 citation statements)

References 42 publications

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“…Thus, targeting PARP-1 in PCa seems promising, given that both DNA repair and AR-mediated transcription depend on PARP-1 function [ 102 ]. Finally, as shown before, PARPi have exhibited their capacity to radiosensitize tumors in PCa preclinical studies [ 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. Together, this opens the research question of combining PARPi, RT, and ADT as a triple therapy.…”

Section: Resultsmentioning

confidence: 80%

“…However, when TP53 and RB1 are both deleted, cell proliferation is increased, which facilitates the appearance of castration resistance and RT resistance. Nevertheless, when combined with a PARP1 inhibitor, radiosensitivity was restored [ 98 ].…”

Section: Resultsmentioning

confidence: 99%

“…Nonetheless, to date, only results from a few preclinical studies are available to evaluate the impact of combining PARPi and RT in PCa. Regarding these studies, it is important to note that the majority of them were performed using cell lines derived from metastatic tissue of advanced PCa [ 92 , 94 , 95 , 96 , 98 ] or had selected mutations [ 92 , 93 , 95 ]. That means that these positive results should be further clinically proven in different PCa settings.…”

Section: Discussionmentioning

confidence: 99%

“…That means that these positive results should be further clinically proven in different PCa settings. Another limitation of these studies is the sample size and the only use of Olaparib [ 92 , 93 , 94 , 95 , 96 , 98 ] among all PARPi. All PARPi act similarly, but each of them has some particularities, such as a different potency for PARP trapping [ 109 ], meaning that these positive results with Olaparib may not be extrapolated to different PARPi.…”

Section: Discussionmentioning

confidence: 99%

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Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review)

Rivero Belenchón,

Congregado Ruiz,

Saez

et al. 2023

IJMS

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PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.

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Section: Resultsmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review)

Rivero Belenchón,

Congregado Ruiz,

Saez

et al. 2023

IJMS

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show abstract

“…In addition, RB1 deficiency is implicated in promoting stemness and metastatic progression [ 6 ] and is associated with poor clinical outcomes in several cancer types [ 7 ]. Interestingly, prostate cancers with p53/pRb loss, resistant to many therapeutics [ 8 ], were radiosensitized by PARP1 inhibitors (PARP1i) [ 9 ], making a combination of PARP1i and APBTI worth clinical testing in p53-/pRb-breast cancers.…”

Section: Patient 2: Exceptional Non-responder (Exnr)mentioning

confidence: 99%

Atypical responses to neoadjuvant chemotherapy combined with accelerated partial breast tumor-directed radiotherapy: two cases and considerations for future clinical trials

Ouidir²,

Grellier³

et al. 2022

Rep Pract Oncol Radiother.

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Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation

Ashrafizadeh,

Zhang,

Tian

et al. 2024

Cancer Metastasis Rev

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Ionizing Radiation Combined with PARP1 Inhibitor Reduces Radioresistance in Prostate Cancer with RB1/TP53 Loss

Cited by 6 publications

References 42 publications

Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review)

Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review)

Atypical responses to neoadjuvant chemotherapy combined with accelerated partial breast tumor-directed radiotherapy: two cases and considerations for future clinical trials

Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation

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