Mesothelioma’s frequent resistance to chemotherapy may be tied to a genetic mutation in some patients, according to a recent study.
Researchers from Switzerland and Germany concluded that pleural mesothelioma patients with a mutated or missing BAP-1 gene all experienced chemoresistance, meaning the cancer was able to tolerate chemical bombardment.
This result suggests that molecular analysis for a faulty or missing BAP-1 gene — which produces specialized proteins — could predict a patient’s response to chemotherapy, enabling oncologists to better tailor treatments to chemoresistant patients.
A Negative Predictor
“Alterations in BAP1 in [malignant pleural mesothelioma] were a negative predictor for response to chemotherapy and could possibly be used as a companion biomarker for treatment decision,” the researchers stated in their paper, which appears in the Feb. 5 edition of Clinical Cancer Research.
“Alterations in BAP1 ... were a negative predictor for response to chemotherapy and could possibly be used as a companion biomarker for treatment decision.” – Study Conclusions
The retrospective analysis examined the records of 28 pleural mesothelioma patients, all of whom had undergone first-line chemotherapy treatment with cisplatin and pemetrexed (which go by the brand names Platinol and Alimta, respectively) followed by surgery.
Despite this being the standard chemotherapy response to a mesothelioma diagnosis, the process leads to a “reduction of tumor size in only a minority of patients,” the researchers noted. This is due in part to chemoresistance.
To test their theory, team members conducted molecular analysis on patient samples, including whole exome and targeted deep sequencing, and also examined patient’s mesothelioma cell lines to determine the status of their BAP-1 genes. They were able to correctly predict chemoresistance based on their analysis in all cases.
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 University Hospital Frankfurt, Johann Wolfgang Goethe University Hospital in Frankfurt, ETH Zurich, the University of Zurich, and its associated hospital.