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Published on: March 20, 2021
Has discovery-based cancer research been a bust?
1Department of Oncology, Clinical Cancer Informatics & Research Centre, The Kinghorn Cancer Centre, Sydney, Australia, repstein@stvincents.com.au.
High expectations for first-generation cancer diagnostics led to slow clinical progress. Second-generation diagnostics must focus on high-signal data, not just statistical patterns, for better anticancer drug development.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- The human genome sequence completion raised hopes for novel anticancer drug development.
- Clinical progress in oncology has been slower than anticipated over the past decade.
Purpose of the Study:
- To analyze the impact of first-generation discovery-based diagnostics on anticancer drug development.
- To propose a framework for more effective second-generation multiplex diagnostics.
Main Methods:
- Review of clinical progress and diagnostic assay performance in oncology.
- Analysis of limitations in first-generation multiplex assays (gene expression profiling, proteomics).
- Identification of key features for second-generation multiplex diagnostics.
Main Results:
- First-generation multiplex assays have yielded limited high-impact therapeutic targets despite prognostic correlations.
- Hypothesis-based single-molecule tests show incremental clinical utility.
- Statistical patterns alone are insufficient for high-impact diagnostic development.
Conclusions:
- Unrealistically high expectations for first-generation diagnostics have hindered progress.
- Second-generation multiplex diagnostics require clinically interpretable, high-signal data.
- Focusing on functional mutations, amplifications, and signaling pathways will advance anticancer drug development.
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