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Drug sensitivity testing including a broad panel of standard and off-label drugs showed that 50% of the patients showed progression-free-survival after 2 months of 3D organoid guided treatment. The primary end-point was set to 40%. The trial was conducted at University Hospital of Southern Denmark, Vejle and published in Journal of Experimental & Clinical Cancer Research.
The current issue of Nature Reviews Cancer features on its cover a personal perspective on the fight against rare cancers. One part of the story of this features the use of an agnostic drug-repurposing screen to do functional precions medicine. This revealed vulnerabilities that were not predicted by the transcriptome, but which helped not only elucidate some important cell biology pathways in the toumor, but have laid the foundation for a clinical trial
3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs require standardization criteria and prospective trials to establish clinical benefits. Innovative trial designs that combine omics and 3D-PTA readouts may lead to more accurate clinical predictors, and an integrated platform that combines diagnostic and therapeutic development will accelerate new treatments for patients with refractory disease.
Although functional precision medicine has the potential to transform cancer care, experts at the American Association for Cancer Research's annual meeting recounted how the present regulatory and reimbursement environment has made it difficult for them to use research findings to inform patient treatment.
Professor Anthony Letai, President of the Society for Functional Precision Medicine explains the concept of functional precision medicine in oncology: we take the patient's living tissue and expose it to drugs, then ask if there is an effect, we can measure that predicts response in vivo. Dr. Letai is convinced that this will be a valuable diagnostic tool, the next step in precision medicine.
Drug testing of patient derived tumor organoids identified high sensitivity to the EGFR targeting drug lapatinib, consistent with HER2 amplification. Remarkably, this patient achieved a complete remission with a combination of EGFR inhibitor trastuzumab and pertuzumab followed by a personalized vaccine, and is currently disease free. This study indicates the potential of functional testing of patient derived tumor cells to identify effective therapies for cancers with poor outcome.
Organoids are self-organizing, expanding 3D cultures derived from stem cells. Using tissue derived from patients, these miniaturized models recapitulate various aspects of patient physiology and disease phenotypes, including genetic profiles and drug sensitivities
The accompanying news story discusses how big Pharma, in this case Roche, saw the light and realizedthat patient derived tumor model, which share both somatic and germlinegenetics of a given patient would be a useful model system for both drug development and precision medicine. It is only a matte of time until others catch on.
A roadblock to acceptance of ex vivo drug testing using patient derived tumor cells is demonstration of clinical utility, specifically prospective evidence of patient response. The attached review by Wensink et al. summarizes findings from 17 different studies and concludes that ‘The currently available results offer an optimistic perspective that individualized tumour response testing using PDO shave clinical validity as a predictive biomarker for cancer patients. The pooled sensitivity and specificity for discriminating patients with a clinical response through PDO-based screening were 0.81 (95% CI 0.69–0.89) and 0.74 (95%CI 0.64–0.82), respectively.'