Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Is It Time to Anticipate the Use of Parp Inhibitors in Prostate Cancer Patients?

Alessandro Sciarra
* ORCID logo ,
Valerio Santarelli
,
Lorenzo Santodirocco
,
Marco Frisenda
ORCID logo ,
Stefano Salciccia
,
Paolo Casale
,
Flavio Forte
,
Gianna Mariotti
,
Martina Moriconi
,
Susanna Cattarino
,
Beatrice Sciarra
,
Giulio Bevilacqua
,
Alessandro Gentilucci
Version 1 : Received: 2 July 2023 / Approved: 3 July 2023 / Online: 3 July 2023 (08:22:22 CEST)

A peer-reviewed article of this Preprint also exists.

Sciarra, A.; Santarelli, V.; Santodirocco, L.; Frisenda, M.; Salciccia, S.; Casale, P.; Forte, F.; Mariotti, G.; Moriconi, M.; Cattarino, S.; Sciarra, B.; Bevilacqua, G.; Gentilucci, A. Is It Time to Anticipate the Use of PARP Inhibition in Prostate Cancer Patients? Curr. Oncol. 2023, 30, 8054-8067. Sciarra, A.; Santarelli, V.; Santodirocco, L.; Frisenda, M.; Salciccia, S.; Casale, P.; Forte, F.; Mariotti, G.; Moriconi, M.; Cattarino, S.; Sciarra, B.; Bevilacqua, G.; Gentilucci, A. Is It Time to Anticipate the Use of PARP Inhibition in Prostate Cancer Patients? Curr. Oncol. 2023, 30, 8054-8067.

Abstract

The possibility of treating more patients for a longer time, has exploded the concept of anticipation in the systemic treatment of metastatic prostate cancer (mPC). The genetic analysis of Damage DNA Repair (DDR) mutations in pathogenetic variants (PV) and the development of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors led to the first valid precision medicine option tailored for mPC. PARP inhibitors are repeating the same evolutionary path experienced for androgen receptor signaling inhibitors (ARSI), starting from the late stage of second line mCRPC in a limited population and time frame. Inevitably also PARP inhibitors will be absorbed by the concept of anticipation and intensification of care. The anticipation of PARP inhibitors in the first line mCRPC therapy is already underway and further one in mHSPC will soon be verified. According to the crosstalk between androgen receptors (AR) and DNA repair, the new message that is emerging is that the combination of PARP inhibitors with ARSI, disconnects PARP from the genetic analysis. Most of the recent trials analyzing PARP inhibitors plus abiraterone or enzalutamide, enrolled first line mCRPC irrespectively to gene PV. The conclusion of the PROPEL trial was that the advantage was independent to PV status, however the highest advantage was reported in BRCA1/2 mutated subgroup. The conclusion of the MAGNITUDE trial was different, with a significant advantage only in the DDR mutated subgroup and the DDR non-mutated was closed for further enrollment. The combination of PARP inhibitors with ARSI represents a significant strategy in the concept of anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR.

Keywords

prostate cancer; PARP inhibitors; DDR gene; CRPC

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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