Oncology
very different responses — owing to tumour heterogeneity, epigenetics, microenvironmental influences, and nongenetic resistance mechanisms. Dr. Letai has highlighted this limitation in
several publications. For example, in his article “Functional precision oncology: testing tumors with drugs to identify vulnerabilities and novel combinations”, he argues that livecell functional assays (exposing patient tumour cells to drugs) offer a complementary readout that integrates all the downstream consequences of molecular state, time-dependent changes, micro-environmental influences, and apoptotic priming.1
In another commentary, “Functional
Precision Medicine: Putting drugs on patient cancer cells and seeing what happens”, Letai discusses why traditional molecular biomarkers often fail to predict response and how functional profiling can provide immediately actionable information.2 In practical terms:
l Molecular profiling can suggest potential targets (for example, an EGFR mutation, BRAF V600E, etc.), but it doesn’t account for how tumour cells manage to survive through complex adaptive mechanisms or how the microenvironment shields them.
l Functional profiling, in contrast, takes live patient-derived tumour cells (or tumour fragments) and treats them ex vivo with a range of drug (or drug combination) perturbations to measure the actual biological response. This captures not only the molecular vulnerability, but also the cell’s functional state (apoptotic readiness, survival circuitry, interactions with stroma, etc.).
Thus, functional profiling moves beyond “what is” the tumour to “what does it do when we hit it with this drug”. That provides a more direct path to clinical decision making — selecting a therapy that has demonstrated sensitivity in that individual’s tumour cells, rather than choosing
based solely on a genomic marker of uncertain functional consequence. In summary, while molecular profiling
remains a foundational tool (and is absolutely necessary), functional precision oncology is differentiated by its capacity to measure actual tumour response in a patient-specific context. It thereby complements genetic/molecular approaches, potentially raising predictive accuracy and reducing the guesswork of treatment selection.
Q. Technology has been developed that uses patient-derived 3D micro-tumours. How closely do these models mimic real tumour behaviour within the human body? A. PreComb’s 3DTwin technology generates patient-derived 3D microtumours that closely recapitulate many aspects of in vivo tumour biology. The system is flexible in terms of the source material: it can work with both low and high numbers of cells, which is critical because the amount of tissue available varies across cancer types.
When cell expansion is required, due to
limited starting material, the resulting 3D microtumour is composed solely of tumour cells. In this case, the model reflects tumour- specific characteristics and the tumour microenvironment, but it lacks other cellular components, such as immune or stromal cells, that are present in the original tumour. When fresh tumour tissue is available, 3DTwin
preserves the full cellular composition, including immune cells. This allows the model not only to assess conventional chemotherapy or targeted therapies, but also immune-oncological drugs, providing a more comprehensive and physiologically relevant readout. In essence, it bridges the gap between
standard 2D culture systems and in vivo tumours by maintaining tumour architecture, heterogeneity, and — when using fresh tissue — critical cell–cell interactions. This makes it
a powerful platform for functional precision oncology, as it more accurately reflects how tumours will respond to therapy in the patient.
Q. How easily could the technology be implemented within hospital laboratories or cancer centres? A. Most functional testing platforms today are offered only through centralised service providers, which can limit accessibility and slow turnaround times. PreComb’s core implementation philosophy is to bring functional testing directly into university hospitals and large cancer centres, enabling cost-efficient and seamless integration into clinical workflows. The on-site platform is fully automated and
includes several key components: an automated tissue dissociation device, an automated screening device, the 3DTwin profiler, and a cloud-based data analysis platform. Together, these elements allow tumour samples to be processed, tested against a panel of therapies, and analysed with minimal hands-on intervention. Tests are fully tailored to the individual patient in collaboration with the treating physician. This decentralised, automated approach allows hospitals to implement functional precision oncology without the logistical challenges of sending samples to external labs, making it feasible to integrate real-time, patient-specific data into clinical decision-making.
Q. Beyond improving clinical outcomes, how might functional cancer profiling help to reduce costs or inefficiencies across healthcare systems? A. Oncology expenditures are rising rapidly, yet many patients continue to receive therapies with limited or no benefit. While biomarker- driven, precision medicine has improved outcomes for some, it remains relevant for only a minority of patients with actionable molecular alterations. Functional Precision Oncology (FPO) offers a scalable, evidence-driven approach to align treatment decisions with both clinical
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www.clinicalservicesjournal.com I March 2026
Tawanboonnak -
stock.adobe.com
Christoph Burgstedt -
stock.adobe.com
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