SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE
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Research Highlights
A systematic analysis of the landscape of synthetic lethality driven precision oncology
Alejandro A. Schäffer^, Youngmin Chung^, Ashwin V. Kammula, Eytan Ruppin#, Joo Sang Lee#
Med
● Synthetic lethality (SL) denotes a genetic interaction between two genes whose co-inactivation is detrimental to cells. As more than 25 years have passed since it has been proposed as a promising way to selectively target cancer vulnerabilities, it is timely to comprehensively assess its impact so far and discuss its future.
● This article analyzes the impact of SL in precision cancer medicine through mid-2022 and discusses its future. To this end we systematically mined the literature and clinical trial data to portray the landscape of the SL-based cancer studies.
● We identified 235 preclinically validated SL pairs and found 1,207 pertinent clinical trials, whose number keeps increasing over time. About one third of these SL clinical trials goes beyond the typically-studied DNA damage response (DDR) pathway, testifying to recent broadening scope of SL applications in clinical oncology. We find that SL oncology trials have a greater success rate than non-SL-based trials. Yet, about 75% of the preclinically validated SL interactions have not yet been tested in clinical trials.
● Dissecting the recent efforts harnessing SL to identify predictive biomarkers, novel therapeutic targets and effective combination therapy, our systematic analysis reinforces the hope that synthetic lethality may serve as a key driver of precision oncology going forward.
● This study was Funded by Samsung Research Funding & Incubation Center of Samsung Electronics, Institute of Information & Communications Technology Planning & Evaluation (IITP), Kwanjeong Educational Foundation.
● This study is published in Med (Cell sister journal, Impact Factor=17).
● This article analyzes the impact of SL in precision cancer medicine through mid-2022 and discusses its future. To this end we systematically mined the literature and clinical trial data to portray the landscape of the SL-based cancer studies.
● We identified 235 preclinically validated SL pairs and found 1,207 pertinent clinical trials, whose number keeps increasing over time. About one third of these SL clinical trials goes beyond the typically-studied DNA damage response (DDR) pathway, testifying to recent broadening scope of SL applications in clinical oncology. We find that SL oncology trials have a greater success rate than non-SL-based trials. Yet, about 75% of the preclinically validated SL interactions have not yet been tested in clinical trials.
● Dissecting the recent efforts harnessing SL to identify predictive biomarkers, novel therapeutic targets and effective combination therapy, our systematic analysis reinforces the hope that synthetic lethality may serve as a key driver of precision oncology going forward.
● This study was Funded by Samsung Research Funding & Incubation Center of Samsung Electronics, Institute of Information & Communications Technology Planning & Evaluation (IITP), Kwanjeong Educational Foundation.
● This study is published in Med (Cell sister journal, Impact Factor=17).