Targeting DNA Damage Response in Prostate and Breast Cancer

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(21), С. 8273 - 8273

Опубликована: Ноя. 4, 2020

Steroid hormone signaling induces vast gene expression programs which necessitate the local formation of transcription factories at regulatory regions and large-scale alterations genome architecture to allow communication among distantly related cis-acting regions. This involves major stress genomic DNA level. Transcriptionally active are generally instable prone breakage due torsional depletion nucleosomes that make more accessible damaging agents. A dedicated damage response (DDR) is therefore essential maintain integrity these exposed The DDR a complex network involving sensor proteins, such as poly(ADP-ribose) polymerase 1 (PARP-1), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), ataxia–telangiectasia-mutated (ATM) ATM Rad3-related (ATR) kinase, central regulators. tight interplay between steroid receptors has been unraveled recently. Several repair factors interact with androgen estrogen support their transcriptional functions. Conversely, both directly control agents involved in DDR. Impaired also exploited by tumors acquire advantageous mutations. Cancer cells often harbor germline or somatic genes, association disease outcome treatment led intensive efforts towards identifying selective inhibitors targeting players this process. PARP-1 now approved for ovarian, breast, prostate cancer specific alterations. Additional DDR-targeting being evaluated clinical studies either single combination treatments eliciting (e.g., radiation therapy, including targeted radiotherapy, chemotherapy) addressing targets maintenance integrity. Recent preclinical findings made dysfunction hormone-dependent -independent breast presented. Importantly, anti-hormonal therapy inhibition potential enhance efficacy but still needs further investigation.

Язык: Английский

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PARP Inhibitors for Ovarian Cancer: Current Indications, Future Combinations, and Novel Assets in Development to Target DNA Damage Repair

American Society of Clinical Oncology Educational Book, Год журнала: 2020, Номер 40, С. e116 - e131

Опубликована: Май 1, 2020

PARP inhibitors (PARPIs) have revolutionized the treatment of epithelial ovarian cancer, first for BRCA-associated and, recently, all cancers serous or high-grade endometrioid subtypes in front line. Although there is hope that PARPIs will help prevent recurrences when used following frontline maintenance, cancer still recur most women, and need active combination strategies as well continued development novel assets, either monotherapy combination, be urgently needed. This review article discusses current indications both recurrent settings, research approaches, finally, ongoing on methods to target DNA damage response an effort exploit common susceptibility repair improve outcomes patients.

Язык: Английский

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CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

Journal of Experimental & Clinical Cancer Research, Год журнала: 2020, Номер 39(1)

Опубликована: Сен. 15, 2020

Abstract Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class selective cell cycle therapeutics that target cyclin D-CDK4/6 complex induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy inhibitors, stimulating further explorations other combination strategies. Multiple preclinical studies indicated CDK4/6 exhibit synergistic effect radiotherapy both in vitro vivo. The principal mechanisms radiosensitization include inhibition DNA damage repair, enhancement apoptosis, blockade progression, which provide rationale for clinical use. also cellular senescence promote anti-tumor immunity, might represent potential radiosensitization. Several small sample preliminarily exhibited well-tolerated toxicity promising efficacy. However, most trials remain recruitment stage. Further work is required seek optimal radiotherapy-drug combinations. In this review, we describe underlying radiosensitizer discuss previous evaluate prospects challenges combination.

Язык: Английский

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Understanding genomics and the immune environment of penile cancer to improve therapy

Nature Reviews Urology, Год журнала: 2020, Номер 17(10), С. 555 - 570

Опубликована: Авг. 18, 2020

Язык: Английский

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Ataxia telangiectasia mutated inhibitor-loaded copper sulfide nanoparticles for low-temperature photothermal therapy of hepatocellular carcinoma

Acta Biomaterialia, Год журнала: 2021, Номер 127, С. 276 - 286

Опубликована: Апрель 1, 2021

Язык: Английский

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