Mesothelioma patients who have a high expression of two encoded proteins — p-mTOR and p-S6RP — tend to enjoy longer mesothelioma survival following extrapleural pneumonectomy.
This appears to be true even when radiation therapy is not administered after the surgery.
Researchers in Japan made this observation in the course of investigating mTOR signal pathway activation in mesothelioma patients who undergo procedures such as extrapleural pneumonectomy.
The protein mTOR — without the “p” in front of it — stands for “mammalian target of rapamycin.” It’s an encoded protein kinase responsible for keeping cell replication and growth in check.
How Mesothelioma Benefits from mTOR
Scientists have noted that in patients with cancers like mesothelioma, the mTOR protein is mutated and becomes overactive. The overactivity promotes mesothelioma tumors by pumping individual cancer cells full of oxygen and growth nutrients.
The mTOR also aids mesothelioma tumor growth by shutting off autophagy — a mechanism that normally helps the body maintain a tight rein on cells. To make matters worse, mTOR helps mesothelioma cells adapt their metabolic functions to changing environmental conditions, such as those created when the immune system launches an attack.
Then there’s s6RP, or ribosomal protein S6. Like mTOR, s6RP — sometimes also spelled rpS6 — is a regulator of cell growth until something causes it to mutate.
In this Japanese study, the researchers focused on mTOR and s6RP when linked to phosphorus, which is what the “p” means when you see it in front of mTOR or s6RP.
Apparently, the presence of p-mTOR and p-s6RP are beneficial counterweights to mutated mTOR and s6RP.
Amount of p-mTOR and p-S6RP in Mesothelioma Patients was Evaluated
The objective of the Japanese study was to evaluate p-mTOR and p-S6RP in mesothelioma patients before and after undergoing chemotherapy and extrapleural pneumonectomy as a pair, or as a pair joined by radiation therapy.
There were 46 patients enrolled in this study. Twenty received chemotherapy and extrapleural pneumonectomy. The remaining 26 received those plus postoperative doses of radiation.
All of this occurred between April 2004 and October 2012. Three times as many men as women participated in the study. The subjects ranged in age from 37 to 71, with the median age just shy of 60.
Almost all of the participants had the epithelial type of mesothelioma. Two had the biphasic type and one the sarcomatoid type.
At the end of the study, the researchers found that the overall mesothelioma survival of these patients as a group was 24.5 month.
But here’s the thing. The ones with the highest levels of either p-S6RP or p-mTOR experienced mesothelioma survival that was at least 50 percent longer than the group average.
The reverse was true as well. Those with the lowest levels of p-S6RP or p-mTOR had mesothelioma survival below the average.
Specifically, mesothelioma patients with high expressions of p-S6RP survived up to nearly 44 months after treatment while those with little or no p-S6RP expression survived up to just over 14 months.
Among the patients with high expressions of p-mTOR, the mesothelioma survival rate topped out at slightly more than 37 months. The mesothelioma survival for patients with little or no p-mTOR expression was 14.4 months.
The researchers discussed these findings at the June meeting of the American Society of Clinical Oncology in Chicago.