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Updated: Aug 5, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Patient cell drug profiling identifies p53-linked vulnerabilities in refractory lymphoid malignancies
Arvid Cederlund1,2, Nona Struyf3, Lucia Rico Pizarro3
1Dept. of Medicine at Huddinge, Karolinska Institutet, Stockholm, Sweden. arvid.cederlund@ki.se.
Abstract:
Relapsed/refractory lymphoid malignancies lack effective treatment selection strategies. We evaluated high-throughput ex vivo drug profiling in 26 patients, achieving successful profiling in 22 cases. We found broad ex vivo resistance to conventional chemotherapy but sensitivity to BH3 mimetics. Notably, p53-aberrant samples showed increased sensitivity to dasatinib and PI3K inhibitors across subtypes. These findings demonstrate feasibility of functional precision medicine pipelines in lymphoid malignancies and identify actionable vulnerabilities warranting further investigation.
Insights
High-throughput drug screening in relapsed/refractory lymphoid malignancies reveals resistance to standard chemotherapy but sensitivity to BH3 mimetics. Functional precision medicine shows promise for identifying targeted therapies like dasatinib and PI3K inhibitors.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Relapsed/refractory lymphoid malignancies present significant therapeutic challenges.
- Current treatment selection strategies are often ineffective for these aggressive cancers.
Purpose of the Study:
- To evaluate the feasibility of high-throughput ex vivo drug profiling for guiding treatment selection in lymphoid malignancies.
- To identify potential therapeutic vulnerabilities in relapsed/refractory lymphoid cancers.
Main Methods:
- Conducted high-throughput ex vivo drug sensitivity and resistance testing on patient-derived tumor cells.
- Analyzed drug responses across various lymphoid malignancy subtypes.
- Correlated drug sensitivity with specific molecular aberrations, such as p53 alterations.
Main Results:
- Successful drug profiling was achieved in 22 out of 26 patients.
- Demonstrated broad ex vivo resistance to conventional chemotherapeutic agents.
- Observed significant sensitivity to BH3 mimetics.
- Identified increased sensitivity to dasatinib and PI3K inhibitors in p53-aberrant samples.
Conclusions:
- Functional precision medicine pipelines are feasible for lymphoid malignancies.
- Ex vivo drug profiling can uncover actionable therapeutic vulnerabilities.
- BH3 mimetics, dasatinib, and PI3K inhibitors represent promising avenues for further clinical investigation.
