Variations in the immune-system-related FAS ligand (FASL) gene may help predict how long a malignant pleural mesothelioma patient who received platinum-based chemotherapy can survive without the disease progressing.
A study in Egypt showed that 45 percent of patients with the FASL-844 CC gene survived progression-free for 18 months after treatment — versus 10 percent of those with the FASL-844 CT/TT gene.
The research, “FAS and FASL genetic polymorphisms impact on clinical outcome of malignant pleural mesothelioma,” was published in OncoTargets and Therapy,
Egypt is experiencing more mesothelioma. Although multimodal therapy consisting of surgery, radiotherapy, and chemotherapy can significantly improve patients’ survival, most patients are diagnosed at an advanced stage, when surgery is no longer an option.
This makes a combination of Platinol (cisplatin) and Alimta (pemetrexed) the standard first-line therapy.
But these agents require the activation of the FAS pathway to trigger cancer-cell death, and studies have shown that treatment outcomes are different in patients with non-small-cell lung cancer and breast cancer, depending on their FAS and FASL variations.
That finding prompted researchers to hypothesize that outcomes for mesothelioma patients undergoing platinum-based chemotherapy could also depend on the gene variations.
The Faculty of Pharmacy at Ain Shams University did a cohort study (NCT02269878) that included 68 malignant pleural mesothelioma patients, 43 men and 25 women, who had been treated with platinum-based chemotherapy.
Forty-six percent of the patients received Platinol or Paraplatin (carboplatin) plus Alimta. The others received Platinol or Paraplatin in combination with Gemzar (gemcitabine).
Researchers checked the connection between two FAS and FASL gene variations, participants’ response to the treatment and their overall survival and disease-progression-free survival rate at 18 months.
One of the gene variations they studied, FAS-670 A>G, was connected with longer survival rates in patients with non-small-cell lung cancer and breast cancer. But researchers found no such correlation with mesothelioma patients.
They also found no association between the FASL-844 C>T gene variation and mesothelioma survival.
But 45 percent of patients with the FASL-844 CC gene variation survived at least 18 months after platinum chemotherapy without seeing their disease progressing, versus 10 percent of patients with FASL-844 CT or TT variations. This suggested that FASL gene variations can help predict mesothelioma treatment outcomes, which, in turn, can help patients decide on treatment options.