Precision medicine for cancer with next-generation functional diagnostics
Open accessAbstract
Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies. Recently, several 'next-generation' functional diagnostic technologies have been reported, including novel methods for tumour manipulation, molecularly precise assays of tumour responses and device-based in situ approaches; these address the limitations of the older generation of chemosensitivity tests. The promise of these new technologies suggests a future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients.
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Organoids have been deployed to identify therapeutic leads in a number of tumors, including rare cancers that are understudied and poorly characterized at the molecular level.
“Organoids are ideally suited for FPM due to their ease of establishment, similarity with the tissue of origin and tractability158,167 and have been deployed to identify therapeutic leads in a number of tumors168, including rare cancers that tend to be understudied and poorly characterized at the molecular level16,151,169,170.”
From Organoids (2022) · cites this paper as [168]
The “Patient-derived organoids” section (page unavailable) describes organoids from pancreatic, prostate and colon cancers and reports that drug screening of colorectal organoids revealed patient-specific vulnerabilities. It does not establish that organoids identified therapeutic leads across those tumor types or in rare, molecularly poorly characterized cancers. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMicroenvironmental interactions are known to affect in vivo drug response, but cells may lose memory of these interactions during ex vivo treatment.
“Microenvironmental interactions are known to influence in vivo drug response, but cellular ‘memory’ of these interactions may degrade during the course of ex vivo treatment9.”
From Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate (2016) · cites this paper as [9]
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- Authors
- Friedman, A. A., Letai, A., Fisher, D. E., & Flaherty, K. T.
- Affiliations
- Harvard University (US)
- Corresponding author
- Friedman, Adam A.
- Venue
- Nature Reviews Cancer
- Published
- 2015-11-05
- Volume
- 15
- Issue
- 12
- Pages
- 747-756
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC4970460
- OpenAlex
- W2176372762
- Cited by
- 570
- References
- 108
- Citations by year
- 2026: 19 · 2025: 43 · 2024: 26 · 2023: 42 · 2022: 41 · 2021: 67 · 2020: 93 · 2019: 63 · 2018: 59 · 2017: 73 · 2016: 43 · 2014: 1
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (UM1CA186709, P01CA066996)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- precision oncology, functional diagnosis, chemosensitivity testing, genotype-phenotype correlation, next-generation sequencing, immune profiling, drug repurposing
- MeSH terms
- Humans, Neoplasms, Genomics, Molecular Diagnostic Techniques, Precision Medicine, High-Throughput Nucleotide Sequencing
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