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Functional (ex vivo) drug testing

Growing a patient's own cancer cells in a dish and testing drugs on them directly, instead of guessing from genetics.

Patient-derived organoids and short-term ex vivo cultures (SEngine PARIS, Cancertain, Xilis, Curesponse) expose live tumour cells to drug panels. Feasibility and correlation with response are established in colorectal, pancreatic, and ovarian cancer; randomised proof of benefit is pending. Complementary to genomics when no actionable mutation exists.

Schematic · not to scale
Patient tumour cells · Drug per well → viability

How it works

Fresh tumour tissue dissociated and cultured in matrix; viability read-outs per drug within 1-3 weeks.

Strengths
  • Phenotype captures what genotype misses
  • Tests combinations
Limitations
  • Take rate and timeline
  • No stroma or immune component in most systems

Key papers

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basicCell 2017
Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without

DepMap is the lookup table drug hunters use to ask: which cancers would die if we blocked this gene, and how would we recognise them? It generated targets such as WRN and PRMT5-MTAP now in clinical trials, and it is public.

Latest papers

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Literature trend145 papers in the last 12 months+42% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this technology: (TITLE:"functional precision medicine" OR ABSTRACT:"functional precision medicine" OR TITLE:"ex vivo drug sensitivity" OR ABSTRACT:"ex vivo drug sensitivity" OR TITLE:"drug sensitivity testing" OR ABSTRACT:"drug sensitivity testing") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Functional (ex vivo) drug testing, not a curated reading list.

Connected

54top

fronts

2
Diagnostics & BiomarkersDrug Discovery Platforms

technologies

6
BH3 profiling (functional apoptosis testing)Biobanking and tissue procurementN-of-1 and rapid platform trialsOrganoid-guided therapy at scalePatient-derived organoidsPDAC organoid pharmacotyping

companies

4
CuresponseSEngine Precision MedicineValius SciencesXilis

institutions

8
Atrium Health Wake Forest Baptist Comprehensive Cancer CenterHUS Comprehensive Cancer Center, Helsinki University HospitalOHSU Knight Cancer InstituteSanford Burnham Prebys Medical Discovery InstituteSydney Children's Hospitals Network / Children's Cancer InstituteUMC Utrecht Cancer CenterUniversity of New Mexico Comprehensive Cancer CenterWellcome Sanger Institute

pathways

1
Synthetic lethality: paired dependencies

terms

3
Cell lineIn vitro and in vivoOrganoid

roadmaps

2
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCsVirtual cell roadmap: from bulk omics to a predictive model of a cancer cell

ideas

20
A bone marrow niche on a chip to study human dormancyA drug screen that only rewards killing sleeping cancer cellsA funded organoid and PDX panel as the go/no-go gate before IND-enabling moneyA public atlas of drug-pair responses across a thousand patient-derived organoidsAn open atlas of collateral sensitivity for every approved targeted drugAn open model bank for the rare tumours nobody has models forAutomated combination discovery: patient-sample screens feeding Bayesian platform trialsDigital twins for treatment selection, validated by predicting before observingEvery drug screen includes standard reference compounds whose performance is publishedEvery resistance mechanism found in a patient must be rebuilt in the laboratoryGrow blood-borne tumour cells to test drugs on the cells that actually spreadGrow each trial patient's tumour as organoids to decide which platform arm opens nextGrow tumour organoids together with the patient's own immune cellsHold organoid drug tests to the same standard as a diagnostic testImplant a tiny device that tests twenty drugs inside the patient's own tumourPatient-derived organoids to pick ADC payloadsRun the mouse or organoid trial at the same time as the human trialTest drugs on freshly cut slices of the patient's own tumourTest drugs on the patient's own cancer cells when there is no trial to joinZebrafish avatars for a drug answer within a week

people

4
Anthony LetaiDavid A. TuvesonEmile VoestJane Cooke Wright

bottlenecks

3
Preclinical models that do not predict peoplePreclinical results do not reproduceToo many combinations to test

key papers

1
Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without