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Precision oncology: origins, optimism, and potential
Vinay Prasad1, Tito Fojo2, Michael Brada3
1Division of Hematology Oncology, Knight Cancer Institute, Department of Public Health and Preventive Medicine, and Center for Health Care Ethics, Oregon Health and Science University, Portland, OR, USA.
Abstract:
Imatinib, the first and arguably the best targeted therapy, became the springboard for developing drugs aimed at molecular targets deemed crucial to tumours. As this development unfolded, a revolution in the speed and cost of genetic sequencing occurred. The result--an armamentarium of drugs and an array of molecular targets--set the stage for precision oncology, a hypothesis that cancer treatment could be markedly improved if therapies were guided by a tumour's genomic alterations. Drawing lessons from the biological basis of cancer and recent empirical investigations, we take a more measured view of precision oncology's promise. Ultimately, the promise is not our concern, but the threshold at which we declare success. We review reports of precision oncology alongside those of precision diagnostics and novel radiotherapy approaches. Although confirmatory evidence is scarce, these interventions have been widely endorsed. We conclude that the current path will probably not be successful or, at a minimum, will have to undergo substantive adjustments before it can be successful. For the sake of patients with cancer, we hope one form of precision oncology will deliver on its promise. However, until confirmatory studies are completed, precision oncology remains unproven, and as such, a hypothesis in need of rigorous testing.
Insights
Precision oncology, guided by tumor genomic alterations, shows promise but requires more rigorous testing. Current approaches may need significant adjustments before demonstrating success for cancer patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Imatinib pioneered targeted cancer therapy, leading to numerous drugs targeting molecular pathways.
- Advances in genetic sequencing accelerated the development of targeted therapies and molecularly defined cancer subtypes.
- Precision oncology hypothesizes improved cancer treatment through therapies guided by tumor genomic alterations.
Purpose of the Study:
- To critically evaluate the current state and promise of precision oncology.
- To review evidence for precision oncology, diagnostics, and radiotherapy.
- To assess the threshold for declaring success in precision oncology interventions.
Main Methods:
- Review of scientific literature on precision oncology, precision diagnostics, and novel radiotherapy.
- Analysis of empirical investigations and biological basis of cancer.
- Assessment of the evidence supporting widespread endorsement of these interventions.
Main Results:
- Confirmatory evidence for precision oncology and related interventions remains scarce despite widespread endorsement.
- The current trajectory of precision oncology is unlikely to succeed without substantial adjustments.
- Precision oncology is currently an unproven hypothesis requiring rigorous testing.
Conclusions:
- Precision oncology, while promising, is not yet proven and requires further validation.
- Substantive adjustments to current approaches are necessary for precision oncology to succeed.
- Rigorous confirmatory studies are essential before precision oncology can be considered a reliable treatment strategy.
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