PARP inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective (Review)

Loizzi, Vera; Ranieri, Girolamo; Laforgia, Mariarita; Gadaleta, Cosmo Damiano; Gargano, G; Kardhashi, Anila; Liso, Maria De; Naglieri, Emanuele; Vecchio, Vittoria Del; Cicinelli, E; Cormio, Gennaro

doi:10.3892/ol.2020.11951

Cited by 18 publications

(13 citation statements)

References 72 publications

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“…El rucaparib es otro de los inhibidores de la PARP disponibles aprobado para el tratamiento del cáncer de ovario en pacientes con mutación BCRA que hayan recibido como mínimo dos líneas previas de tratamiento 54 . El estudio ARIEL 3 valoró la eficacia y seguridad del rucaparib en pacientes con cáncer de ovario de alto grado sensible a platino que había recidivado después de al menos dos líneas de quimioterapia con platino 55 .…”

Section: Inhibidores De La Parpunclassified

Recomendaciones sobre el tratamiento farmacológico del cáncer de ovario epitelial en México

Gallardo‐Rincón¹,

Bahena-González²,

Álvarez³

et al. 2023

GMM

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Ovarian cancer is the third most frequent gynaecological malignancy worldwide and in Mexico, with a high mortality rate, due to that in many cases its diagnosis is made in advanced stages. Prognosis is important for determining the subtype and the degree of evolution. During lasts years, the management of ovarian cancer has undergone an important evolution with the incorporation of new therapeutic options, which in turn represent an increase in the survival of these patients. We present recommendations for the management of ovarian cancer developed by an expert panel Mexican based on available evidence so far and the characteristics of health care in the country.

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Section: Inhibidores De La Parpunclassified

Recomendaciones sobre el tratamiento farmacológico del cáncer de ovario epitelial en México

Gallardo‐Rincón¹,

Bahena-González²,

Álvarez³

et al. 2023

GMM

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“…The proportion of germline variants in any of the genes other than BRCA1 / 2 accounted for 6% of the total cases examined, which, in turn, accounted for one-third of the patients with germline variants in their study [ 82 ]. In tumors with germline alterations of HR-related genes, there are emerging new concepts termed as BRCAness, phenocopies of BRCA1 / 2 defects, expressing communal phenotypes such as the organs in which malignancy develops and the potential clinical responses to platinum-based therapies or vulnerability to poly(ADP-ribose) polymerase inhibitors (PARPi) [ 83 , 84 , 85 ]. With respect to the penetrance in each type of cancer, BRCA1 / 2 is known to be the strongest factor responsible and therefore, is categorized as a high-risk genetic factor in imparting susceptibility to specific types of cancer.…”

Section: Hr-based Precision Oncology For Hereditary Tumor Clinicsmentioning

confidence: 99%

Homologous Recombination Deficiencies and Hereditary Tumors

Yamamoto

Hirasawa

2021

IJMS

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Homologous recombination (HR) is a vital process for repairing DNA double-strand breaks. Germline variants in the HR pathway, comprising at least 10 genes, such as BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK2, NBS1(NBN), PALB2, RAD51C, and RAD51D, lead to inherited susceptibility to specific types of cancers, including those of the breast, ovaries, prostate, and pancreas. The penetrance of germline pathogenic variants of each gene varies, whereas all their associated protein products are indispensable for maintaining a high-fidelity DNA repair system by HR. The present review summarizes the basic molecular mechanisms and components that collectively play a role in maintaining genomic integrity against DNA double-strand damage and their clinical implications on each type of hereditary tumor.

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“…Angiogenesis is a significant driver of the progression and development of epithelial ovarian cancer, and it is the main anti-tumor treatment target [40]. Since 2011, anti-vascular endothelial growth factor treatment, in association with bevacizumab, paclitaxel, and carboplatin, has been the principal therapy by using monoclonal antibodies for patients with metastatic and locally advanced epithelial ovarian cancer [41,42]. Through hypoxia-inducible factor-1α, the PARP1 pathway is capable of controlling gene expression and managing angiogenesis.…”

Section: Biological Association Between Parp and Angiogenesis Preventionmentioning

confidence: 99%

BRCA Mutations and PARP Inhibitors in Breast and/or Ovarian Cancer Patients

Gari¹,

Rawas²,

Mufti³

et al. 2021

Int j pharm res allied sci

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BRCA (BReast CAncer gene) mutations are considered strong risk factors in females and males cancers, these include breast, male breast (although rare), ovarian, prostate, pancreatic, and melanoma skin cancers. This paper reviews the literature concerning the association between BRCA and the response rate to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) in breast and ovarian cancer patients. Recent evidence shows that PARPi can be utilized as a base for monotherapy strategies and a broad spectrum of molecular cancers. BRCA1/BRCA2 mutations enhance the risk for developing ovarian and breast cancer, amongst others that are caused either by somatic or germline mutations. PARPi begins the repair pathway of the single-stranded DNA breakage, which is considered the most common form of damage, with the help of certain key PARP enzymes. Olaparib was the first approved PARPi drug by the European Medicine Agency (EMA) and the American Food and Drug Administration (FDA) to treat patients with recurrent BRCA-mutated epithelial ovarian cancer after receiving three or more previous chemotherapies. Furthermore, the FDA approved olaparib to manage patients with HER2-negative, BRCA-mutated, and metastatic breast cancers managed previously through chemotherapy. The studies show that using olaparib for maintenance treatment results in a significantly longer progression-free survival and a slightly better overall survival rate among breast and ovarian cancer patients. Certain studies have shown that olaparib maintenance treatment was mostly prosperous and well-endured among advanced BRCA-mutated ovarian cancers.

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PARP inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective (Review)

Cited by 18 publications

References 72 publications

Recomendaciones sobre el tratamiento farmacológico del cáncer de ovario epitelial en México

Recomendaciones sobre el tratamiento farmacológico del cáncer de ovario epitelial en México

Homologous Recombination Deficiencies and Hereditary Tumors

BRCA Mutations and PARP Inhibitors in Breast and/or Ovarian Cancer Patients

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