Most cancer drugs fail in humans because the lab models used to test them—mice, cell lines, and artificial tissues—do not replicate the real tumour environment. INTREPID aims to make live human tumour cultures the standard preclinical tool instead. The core problem is that existing models miss key features of real cancers: the surrounding stroma, immune cells, blood vessels, and genetic diversity across patients. Live tumour slices, taken directly from surgery, preserve all of this. But researchers rarely use them because the methods are not standardised, tissue is hard to access, and there is no shared community of practice. If INTREPID succeeds, it will deliver validated protocols, automated quality controls, and a perfusion system that keeps tissue alive longer in multi-well plates. It will also demonstrate that these cultures can test advanced therapies such as cell and RNA-based drugs. The result would be a shift away from animal models toward human-relevant, reproducible data that better predicts how diverse patient populations will respond to treatment. This is not a breakthrough in itself—it is an infrastructure project that removes the barriers preventing a more realistic model from becoming routine.
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Context Understanding the spectrum of cancer complexities and their translation to therapeutic benefit is intimately dependent on preclinical models that accurately reflect tumour ecosystems, heterogeneity and patient diversity. This cannot be achieved with existing preclinical models. Challenge the project addresses Existing preclinical models for cancer including genetically inbred mice, Patient-Derived Xenograft (PDX) mice, organoids and multi-cellular models cannot capture the full spectrum of cancer complexity needed for driving effective therapeutic translation. Live human tumour cultures offer a powerful alternative as they preserve the microenvironment of real tumours including stromal elements, immune infiltrates and vasculature networks while also accommodating sub-clonal/clonal heterogeneity and patient diversity. Despite this potential, live tumour culture methods have not, as yet, been widely adopted in the cancer research community, with explanations ranging from a reluctance to change reliance on existing models to lack of awareness, lack of confidence in tissue stability and limited access to fresh patient tissue. INTREPID will tackle the barriers associated with widespread adoption of live human tumour culture models to drive a step change in their use in the cancer research community. Aims and objectives: Aim: By implementing INTREPID we aim to ensure that live human tumour culture methodologies are widely adopted and sustained as models of choice for basic and applied cancer studies in academia and industry. Objectives: Work Package 1: Build the INTREPID community. We will bring together a cluster of interdisciplinary UK experts in live human tumour culture methodologies to share best practice, knowledge and expertise. This will provide the critical mass required for model validation and adoption. Work Package 2. Technical development. We will use our combined interdisciplinary expertise to optimise and advance live in vitro human tumour cultures including: a) Optimisation and standardisation of SOPs for a wide range of primary tumours and lymph node metastasis samples. We will define standard quality metrics for tissue and establish reproducibility measures between sites. We will develop validation datasets for essential applications, enabling future users to benchmark their work, and establish automated quality control protocols. b) Advance bioengineering approaches to incorporate intravascular perfusion into the multi-well format to overcome the “brick wall” threshold of short-term cultures. Technology development will incorporate ‘in line’ monitoring of live tissue to allow higher order data accumulation on each sample to streamline outputs. The platform will be designed for adoption by non-engineering labs to enhance clinical translation. Work Package 3. Validation of advanced therapy delivery. We will undertake studies designed to validate live tumour cultures for delivery of advanced therapies, specifically cell- and RNA- based therapies. This will place live tumour culture approaches at the cutting edge of drug discovery and development programmes. Work Package 4. Knowledge mobilisation. INTREPID will pioneer a program of knowledge mobilisation and engagement in live human tumour culture approaches and applications to build capacity, support adoption and promote open-source data/tools. This will include activities in technical skills training, communication and dissemination as well as industrial and life sciences liaison to educate the wider academic and industrial sectors. Potential applications and benefits INTREPID will stimulate wider uptake of live human tissue culture approaches to: a) drive a step change in reliance on animal models for basic and applied cancer studies; b) generate data that is more clinically relevant, sustainable and translatable for therapeutic benefit across diverse patient populations.
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