Specific demonstration of drug-induced tumour cell apoptosis in human xenografts models using a plasma biomarker

Area of Science:

• Oncology
• Biomarker Discovery
• Pharmacodynamics

Background:

• Pharmacodynamic (PD) assays are crucial for evaluating drug efficacy before clinical trials.
• Current PD assays often require invasive tissue biopsies to measure drug response.
• There is a need for non-invasive methods to assess drug-induced apoptosis.

Purpose of the Study:

• To evaluate the M30-Apoptosense ELISA assay for detecting drug-induced apoptosis in preclinical cancer models.
• To determine the assay's ability to measure caspase-cleaved cytokeratin 18 (CK18) in plasma.
• To establish the assay's utility in translational studies of anticancer drugs.

Main Methods:

• The M30-Apoptosense ELISA assay was used to quantify caspase-cleaved CK18 in plasma samples.
• Human tumor xenografts in rodents were treated with anticancer drugs.
• The assay's detection of human, mouse, and rat CK18 cleavage products was assessed.

Main Results:

• The M30-Apoptosense ELISA specifically detected human caspase-cleaved CK18, with low affinity for rodent forms.
• Increased levels of caspase-cleaved CK18 were observed in plasma from xenograft models treated with anticancer drugs.
• The presence of caspase-cleaved CK18 in plasma correlated with apoptosis in tumor tissues and cell cultures.

Conclusions:

• The M30-Apoptosense ELISA is a valuable tool for measuring drug-induced apoptosis in human tumor xenografts using plasma.
• The assay facilitates translational research by enabling non-invasive monitoring of therapeutic response in preclinical models and patients.
• This PD assay supports the advancement of anticancer drugs by providing a robust measure of tumor response.