A new study finds that a genetic mutation present in some patients may be responsible for mesothelioma chemotherapy resistance.
Scientists in Switzerland and Germany have determined that all pleural mesothelioma patients with a missing or mutated (defective) BAP-1 (BRCA1-associated protein-1) gene are chemoresistant, meaning the cancer is not successfully responding to chemical therapy.
The finding implies that molecular analysis for a defective or absent BAP-1 gene, which codes for proteins that carry out specific tasks — could serve as readout to predict chemoresistance in a patient so doctors can ‘personalize’ chemotherapy treatment to-his-or-her chemo-resistant status.
A Negative Predictor
BAP1 had already been linked to poor responses to chemotherapy, the researchers reported in their article, published in the Feb. 5 Clinical Cancer Research.
“Mutations in BAP1… constituted an adverse predictor of chemotherapy response and could be a potential companion biomarker for therapy choice.”
The retrospective study looked at records from 28 pleural mesothelioma patients who had been treated with first-line chemotherapy consisting of Platinol and Alimta, both brand names for cisplatin and pemetrexed, respectively, before surgery.
That is the usual response of mesothelioma to this step in chemotherapy, but it “results in a measurable decrease in tumor size in only a few patients,” according to the researchers. Well, in part that is due to chemoresistance.
Perfect Record
To this end, the researchers performed molecular analysis on patient samples, such as whole exome and targeted deep sequencing, as well as studies of mesothelioma cell lines derived from patients to evaluate the status of their BAP-1 genes. In other words, their analysis allowed them to accurately predict chemoresistance in every case.
This result was then confirmed by running tests on cell lines in a separate group of 39 patients, the study says.
The researchers hypothesize that modified or missing BAP-1 genes may confer chemoresistance by inhibiting the natural death of cancerous cells or by rewriting gene expression. However, this was based on laboratory tests, rather than testing it in the human body.
The group of 12 researchers hailed from the University Hospital Frankfurt, Johann Wolfgang Goethe University Hospital in Frankfurt, ETH Zurich, the University of Zurich, and its associated hospitals.
