High-dose short-term osimertinib treatment is effective in patient-derived metastatic colorectal cancer organoids.

ABSTRACT:

Background

Most tyrosine kinase inhibitors (TKIs) have failed in clinical trials for metastatic colorectal cancer (mCRC). To leverage the additional lower-affinity targets that most TKIs have, high-dose regimens that trigger efficacy are explored. Here, we studied unprecedented drug exposure-response relationships in vitro using mCRC patient-derived tumour organoids (PDTOs).

Methods

We investigated the cytotoxic anti-tumour effect of high-dose, short-term (HDST) TKI treatment on 5 PDTOs. Sunitinib, cediranib and osimertinib were selected based on favourable physicochemical and pharmacokinetic properties. Intra-tumoroid TKI concentrations were measured using a clinically validated LC/MS-MS method. Cell death was determined using an enzyme activity assay, immunofluorescent sta

SUBMITTER: Iyer KK 

PROVIDER: S-EPMC11523998 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature