Exploiting synthetic lethality to target BRCA1/2-deficient tumors: where we stand
| العنوان: | Exploiting synthetic lethality to target BRCA1/2-deficient tumors: where we stand |
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| المؤلفون: | Razq Hakem, Arash Algouneh, Parasvi S. Patel |
| المصدر: | Oncogene. 40:3001-3014 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, DNA Polymerase Theta, Synthetic lethality, Biology, Endodeoxyribonuclease, medicine.disease, Phenotype, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Fanconi anemia, 030220 oncology & carcinogenesis, Genetics, Cancer research, biology.protein, medicine, Lethality, Molecular Biology, Gene, Polymerase |
| الوصف: | The principle of synthetic lethality, which refers to the loss of viability resulting from the disruption of two genes, which, individually, do not cause lethality, has become an attractive target approach due to the development and clinical success of Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). In this review, we present the most recent findings on the use of PARPi in the clinic, which are currently approved for second-line therapy for advanced ovarian and breast cancer associated with mutations of BRCA1 or BRCA2 (BRCA1/2) genes. PARPi efficacy, however, appears to be limited by acquired and inherent resistance, highlighting the need for alternative and synergistic targets to eliminate these tumors. Here, we explore other identified synthetic lethal interactors of BRCA1/2, including DNA polymerase theta (POLQ), Fanconi anemia complementation group D2 (FANDC2), radiation sensitive 52 (RAD52), Flap structure-specific endonuclease 1 (FEN1), and apurinic/apyrimidinic endodeoxyribonuclease 2 (APE2), as well as other protein and nonprotein targets, for BRCA1/2-mutated cancers and their implications for future therapies. A wealth of information now exists for phenotypic and functional characterization of these novel synthetic lethal interactors of BRCA1/2, and leveraging these findings can pave the way for the development of new targeted therapies for patients suffering from these cancers. |
| تدمد: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-021-01744-2 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::a56d8c8012153c7e1a94bb8c543feccf https://doi.org/10.1038/s41388-021-01744-2 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi...........a56d8c8012153c7e1a94bb8c543feccf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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| DOI: | 10.1038/s41388-021-01744-2 |