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Combination Strategies for Immune Checkpoint Inhibitors in PBRM1-mutant Renal Cell Carcinoma: To PARP or Not To PARP?

Authors:
Elena V Demidova Pooja Ghatalia Sanjeevani Arora

Eur Urol 2022 02 6;81(2):149-150. Epub 2021 Nov 6.

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.10.028DOI Listing
February 2022

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Similar Publications

PARP1 and XRCC1 exhibit a reciprocal relationship in genotoxic stress response.

Authors:
Julia M Reber Jovana Božić-Petković Michelle Lippmann Marvin Mazzardo Asisa Dilger Rebecca Warmers Alexander Bürkle Aswin Mangerich

Cell Biol Toxicol 2022 Jul 1. Epub 2022 Jul 1.

Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Constance, Germany.

PARP1 (aka ARTD1) acts as a prime sensor of cellular genotoxic stress response. PARP1 detects DNA strand breaks and subsequently catalyzes the formation of poly(ADP-ribose) (PAR), which leads to the recruitment of the scaffold protein XRCC1 during base excision and single strand break repair and the assembly of multi-protein complexes to promote DNA repair. Here, we reveal that the recruitment of either protein to sites of DNA damage is impeded in the absence of the other, indicating a strong reciprocal relationship between the two DNA repair factors during genotoxic stress response. Read More

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July 2022
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Metastatic Castration-Resistant Prostate Cancer with BRCA2 Mutation: The Challenge Incorporating PARP Inhibitors and Platinum in Treatment Sequencing.

Authors:
Inês Nogueira Costa Joana Reis Sara Meireles Maria João Ribeiro Miguel Barbosa Isabel Augusto

Eur J Case Rep Intern Med 2022 24;9(5):003331. Epub 2022 May 24.

Medical Oncology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal.

Prostate cancer is the second most frequent malignancy in men worldwide. Despite the improvement in survival achieved by increasingly early diagnosis and advances in treatment, it is still associated with high mortality. Because of its molecular heterogeneity, there is a need to identify genetic alterations in order to apply targeted therapies. Read More

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May 2022
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Cancer cell-autonomous overactivation of PARP1 compromises immunosurveillance in non-small cell lung cancer.

Authors:
Pan Juncheng Adrien Joseph Antoine Lafarge Isabelle Martins Florine Obrist Jonathan Pol Ester Saavedra Sijing Li Allan Sauvat Giulia Cerrato Sarah Lévesque Marion Leduc Oliver Kepp Sylvère Durand Fanny Aprahamian Nitharsshini Nirmalathansan Judith Michels Guido Kroemer Maria Castedo

J Immunother Cancer 2022 Jun;10(6)

Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, INSERM UMR1138, Paris, France

Background: High activity of poly(ADP-ribose) polymerase-1 (PARP1) in non-small cell lung cancer (NSCLC) cells leads to an increase in immunohistochemically detectable PAR, correlating with poor prognosis in patients with NSCLC, as well as reduced tumor infiltration by cytotoxic T lymphocytes (CTLs). Intrigued by this observation, we decided to determine whether PARP1 activity in NSCLC cells may cause an alteration of anticancer immunosurveillance.

Methods: Continuous culture of mouse NSCLC cells in the presence of cisplatin led to the generation of cisplatin-resistant PAR clones. Read More

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June 2022
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Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial.

Authors:
J S Frenel J W Kim N Aryal R Asher D Berton L Vidal P Pautier J A Ledermann R T Penson A M Oza J Korach T Huzarski S Pignata N Colombo T W Park-Simon K Tamura G S Sonke A E Freimund C K Lee E Pujade-Lauraine

Ann Oncol 2022 Jun 27. Epub 2022 Jun 27.

ARCAGY-GINECO, Paris, France.

Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown.

Patients And Methods: We conducted post-hoc hypothesis-generating analysis of SOLO-2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. Read More

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June 2022
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Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D.

Authors:
R Graffeo H Q Rana F Conforti B Bonanni M J Cardoso S Paluch-Shimon O Pagani A Goldhirsch A H Partridge M Lambertini J E Garber

Breast 2022 Jun 18;65:32-40. Epub 2022 Jun 18.

Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, USA.

Breast cancer risk associated with germline likely pathogenic/pathogenic variants (PV) varies by gene, often by penetrance (high >50% or moderate 20-50%), and specific locus. Germline PVs in BRCA1 and BRCA2 play important roles in the development of breast and ovarian cancer in particular, as well as in other cancers such as pancreatic and prostate cancers and melanoma. Recent studies suggest that other cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C and RAD51D confer differential risks of breast and other specific cancers. Read More

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June 2022
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