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Published on: September 19, 2019
Tumor heterogeneity and personalized cancer medicine: are we being outnumbered?
Geert A Cirkel1, Christa G Gadellaa-van Hooijdonk, Marco J Koudijs
1Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Abstract:
Tumor heterogeneity is regarded as a major obstacle to successful personalized cancer medicine. The lack of reliable response assays reflective of in vivo tumor heterogeneity and associated resistance mechanisms hampers identification of reliable biomarkers. By contrast, oncogene addiction and paracrine signaling enable systemic responses despite tumor heterogeneity. This strengthens researchers in their efforts towards personalized cancer medicine. Given the fact that tumor heterogeneity is an integral part of cancer evolution, diagnostic tools need to be developed in order to better understand the dynamics within a tumor. Ultra-deep sequencing may reveal future resistant clones within a (liquid) tumor biopsy. On-treatment biopsies may provide insight into intrinsic or acquired drug resistance. Subsequently, upfront combinatorial treatment or sequential therapy strategies may forestall drug resistance and improve patient outcome. Finally, innovative response assays, such as organoid cultures or patient-derived tumor xenografts, provide an extra dimension to correlate molecular profiles with drug efficacy and control cancer growth.
Insights
Tumor heterogeneity challenges personalized cancer medicine. New diagnostic tools and response assays are crucial for understanding tumor evolution, predicting resistance, and improving patient outcomes with targeted therapies.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Tumor heterogeneity presents a significant hurdle for effective personalized cancer medicine.
- Current response assays often fail to capture in vivo tumor heterogeneity and drug resistance mechanisms, hindering biomarker discovery.
Purpose of the Study:
- To explore strategies for overcoming tumor heterogeneity in personalized cancer medicine.
- To highlight the importance of advanced diagnostic tools and response assays for understanding cancer evolution and drug resistance.
Main Methods:
- Review of current challenges and advancements in personalized cancer medicine.
- Discussion of diagnostic approaches including ultra-deep sequencing and on-treatment biopsies.
- Exploration of innovative response assays like organoid cultures and patient-derived tumor xenografts.
Main Results:
- Oncogene addiction and paracrine signaling offer systemic responses despite heterogeneity.
- Advanced sequencing and biopsy techniques can identify resistant clones and resistance mechanisms.
- Innovative assays correlate molecular profiles with drug efficacy.
Conclusions:
- Developing robust diagnostic tools and response assays is essential to address tumor heterogeneity.
- Combinatorial or sequential therapies may preemptively manage drug resistance.
- Personalized cancer medicine requires a deeper understanding of tumor dynamics and drug response.
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