Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial

Bono, Johann S. de; Mehra, Niven; Scagliotti, Giorgio Vittorio; Castro, Elena; Dorff, Tanya B.; Stirling, Adam; Stenzl, Arnulf; Fleming, Mark T.; Higano, Celestia S.; Saad, Fred; Buttigliero, Consuelo; Oort, Inge M. van; Laird, A. Douglas; Mata, Marielena; Chen, Hsiang-Chun; Healy, Cynthia G.; Czibere, Akos; Fizazi, Karim

doi:10.1016/s1470-2045(21)00376-4

Cited by 189 publications

(162 citation statements)

References 30 publications

(25 reference statements)

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“…While initially effective, patients with metastatic PCa receiving ADT will eventually develop resistance and progress to inevitably lethal metastatic castration-resistant prostate cancer (mCRPC) [ 4 ]. The last decade has seen an expansion of drugs to prolong the life of mCRPC, including second-generation androgen receptor (AR) inhibitors, the chemotherapeutic taxane cabazitaxel and PARP inhibitors for tumors with defects in DNA-damage-repair proteins such as BRCA1/2 and ATM [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. However, identifying new therapeutic targets for mCRPC patients and providing new genetic markers for existing therapies remain a critical challenge.…”

Section: Introductionmentioning

confidence: 99%

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

Tsujino

Komura

Inamoto

et al. 2021

IJMS

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Prostate cancer (PCa) is one of the common malignancies in male adults. Recent advances in omics technology, especially in next-generation sequencing, have increased the opportunity to identify genes that correlate with cancer diseases, including PCa. In addition, a genetic screen based on CRISPR/Cas9 technology has elucidated the mechanisms of cancer progression and drug resistance, which in turn has enabled the discovery of new targets as potential genes for new therapeutic targets. In the era of precision medicine, such knowledge is crucial for clinicians in their decision-making regarding patient treatment. In this review, we focus on how CRISPR screen for PCa performed to date has contributed to the identification of biologically critical and clinically relevant target genes.

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Section: Introductionmentioning

confidence: 99%

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

Tsujino

Komura

Inamoto

et al. 2021

IJMS

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“…Breast and ovarian cancers respond to PARP inhibition when harboring HRR pathway deficiency. Talazoparib, a more potent PARP inhibitor than Olaparib and Rucaparib, is under study to test for efficacy against mCRPC with aberrant HRR [ 43 ]. Talazoparib is approved for HER2-negative breast cancer with germline BRCA1 / BRCA2 mutation.…”

Section: Current Prostate Cancer Therapiesmentioning

confidence: 99%

Precision Targets for Intercepting the Lethal Progression of Prostate Cancer: Potential Avenues for Personalized Therapy

Christenson

Song

Liu

et al. 2022

Cancers

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Organ-confined prostate cancer of low-grade histopathology is managed with radiation, surgery, active surveillance, or watchful waiting and exhibits a 5-year overall survival (OS) of 95%, while metastatic prostate cancer (PCa) is incurable, holding a 5-year OS of 30%. Treatment options for advanced PCa—metastatic and non-metastatic—include hormone therapy that inactivates androgen receptor (AR) signaling, chemotherapy and genome-targeted therapy entailing synthetic lethality of tumor cells exhibiting aberrant DNA damage response, and immune checkpoint inhibition (ICI), which suppresses tumors with genomic microsatellite instability and/or deficient mismatch repair. Cancer genome sequencing uncovered novel somatic and germline mutations, while mechanistic studies are revealing their pathological consequences. A microRNA has shown biomarker potential for stratifying patients who may benefit from angiogenesis inhibition prior to ICI. A 22-gene expression signature may select high-risk localized PCa, which would not additionally benefit from post-radiation hormone therapy. We present an up-to-date review of the molecular and therapeutic aspects of PCa, highlight genomic alterations leading to AR upregulation and discuss AR-degrading molecules as promising anti-AR therapeutics. New biomarkers and druggable targets are shaping innovative intervention strategies against high-risk localized and metastatic PCa, including AR-independent small cell-neuroendocrine carcinoma, while presenting individualized treatment opportunities through improved design and precision targeting.

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“…Studies have shown that PARP inhibitors may block prostate cancer disease progression to castration resistance prostate cancer, with reduced castration resistance growth and delayed development from local disease to mCRPC [ 111 ]. Furthermore, PARP inhibitors may also be effective in prostate cancer with genes indirectly involved in the HR pathway that are similar to BRCA mutations [ 119 ]. Several PARP inhibitors have been developed and investigated in clinical research, six of which are summarized in Table 2 .…”

Section: Implications For the Treatmentmentioning

confidence: 99%

BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations

Shah

Rachmat

Enyioma

et al. 2021

IJMS

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Prostate cancer ranks fifth in cancer-related mortality in men worldwide. DNA damage is implicated in cancer and DNA damage response (DDR) pathways are in place against this to maintain genomic stability. Impaired DDR pathways play a role in prostate carcinogenesis and germline or somatic mutations in DDR genes have been found in both primary and metastatic prostate cancer. Among these, BRCA mutations have been found to be especially clinically relevant with a role for germline or somatic testing. Prostate cancer with DDR defects may be sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors which target proteins in a process called PARylation. Initially they were used to target BRCA-mutated tumor cells in a process of synthetic lethality. However, recent studies have found potential for PARP inhibitors in a variety of other genetic settings. In this review, we explore the mechanisms of DNA repair, potential for genomic analysis of prostate cancer and therapeutics of PARP inhibitors along with their safety profile.

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Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial

Cited by 189 publications

References 30 publications

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

Precision Targets for Intercepting the Lethal Progression of Prostate Cancer: Potential Avenues for Personalized Therapy

BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations

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