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Updated: Aug 21, 2026
High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids
Published on: June 14, 2021
Ex vivo therapeutic index by drug sensitivity assay using fresh human normal and tumor cells
Andrew G Bosanquet1, Philip B Bell
1Bath Cancer Research, Royal United Hospital, Bath BA1 3NG, UK. agb@caltri.org
Abstract:
Toxicity is a major deterrent to achieving substantial improvements in cancer management, since most anticancer drugs inadequately distinguish normal and neoplastic tissues. Improving the differential between beneficial and toxic effects of therapy--therapeutic index--is a major clinical objective, but therapeutic index for cytotoxic drugs is narrow. Fresh tumor and normal cells from 59 patients with acute myeloid leukemia, non-Hodgkin's lymphoma, ovarian cancer and cancers of unknown origin were tested for ex vivo drug sensitivity using apoptosis by morphology assays. Drugs tested included carboplatin, doxorubicin, vincristine, cytarabine, fludarabine, mafosfamide and etoposide. Therapeutic index was derived from the ratio of normal and tumor cell LC90s. Individual patient therapeutic index varied markedly for different drugs and drug therapeutic index varied from patient to patient ranging from extremely unfavourable (<0.001) through excellent (>1000) reflecting patient heterogeneity. Therapeutic index for each drug was consistent with clinical expectations. Significantly, there was no relationship between normal and tumor cell LC90s. We conclude that further laboratory and clinical evaluation is required but the derived ex vivo therapeutic index could enhance choice of chemotherapy by reducing toxicity and/or improving efficacy.
Insights
This study assessed ex vivo drug sensitivity in cancer patients. A novel therapeutic index calculation could guide chemotherapy selection, potentially reducing toxicity and improving treatment efficacy.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Chemotherapy toxicity limits cancer treatment efficacy.
- A narrow therapeutic index (TI) for cytotoxic drugs necessitates improved drug selection.
- Distinguishing between normal and neoplastic tissue sensitivity is crucial for effective cancer management.
Purpose of the Study:
- To evaluate ex vivo drug sensitivity in cancer patients.
- To derive a therapeutic index (TI) for various anticancer drugs.
- To explore the potential of ex vivo TI to guide chemotherapy choices.
Main Methods:
- Tested ex vivo drug sensitivity of fresh tumor and normal cells from 59 patients across multiple cancer types.
- Utilized apoptosis by morphology assays for drug sensitivity.
- Calculated TI as the ratio of normal to tumor cell LC90s for drugs including carboplatin, doxorubicin, and etoposide.
Main Results:
- Significant patient and drug variability in therapeutic index (TI) was observed, ranging from unfavorable (<0.001) to excellent (>1000).
- Individual patient TI varied considerably, highlighting patient heterogeneity.
- No correlation was found between normal and tumor cell drug sensitivity (LC90s).
Conclusions:
- The derived ex vivo therapeutic index (TI) shows promise for enhancing chemotherapy selection.
- This approach could potentially reduce treatment toxicity and improve anticancer drug efficacy.
- Further laboratory and clinical validation of the ex vivo TI is warranted.
