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Ex vivo drug response profiling is a powerful tool to study genotype–drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641). We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers.
Here we describe a case study of a patient with low grade serious ovarian cancer who underwent two rounds of chemotherapy and two surgeries. Despite this, her cancer progressed to the point that she was in rapid decline and entering hospice care. Drug testing on tumor organoids derived from the second surgical resection showed exceptional sensitivity to the BTK inhibitor ibrutinib. Although ibrutinib is not FDA approved for the treatment of ovarian cancer, the tumor board and oncologist recommended and requested its off-label use for this case. Following daily ibrutinib as a mono therapy, the patient exhibited a dramatic and prolonged clinical response, resulting in stable disease for >24 months.
Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors.
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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.