A remarkable computer model focused on decoding the complex genetic interactions found in pleural mesothelioma cases could give researchers insight into future treatments for the disease, according to a new study.
A joint U.S.-India research team has developed an “interactome” that lets anyone map out the complex web of genetic-level interactions taking place in mesothelioma patients’ bodies. More specifically, the program focuses on interactions between proteins, which are expressed by genes, and the basis for the burgeoning field of immunotherapy, such as checkpoint inhibitor drugs.
According to the team, only 10-15 percent of protein-to-protein interactions within their mesothelioma-focused database are known. “For nearly half of the human proteins, not even a single [protein-to-protein interaction] is currently known,” they noted in their report, which appeared April 1 in a special mesothelioma-focused edition of Cancers.
The interactome is a fully interactive model which lists 62 different genes that interact with malignant pleural mesothelioma, connected in a spider-web pattern by hundreds of protein-based interactions.
The team — which included a researcher from the Indian Institute of Science in Bangalore, ones from the University of Pittsburgh in Pennsylvania and a representative from the Center for Disease Control and Prevention’s National Institute of Occupational Safety and Health — used the interactome to map out 2,459 previously known protein-to-protein interactions. The team then fed that data into an algorithm that calculated 364 new protein-to-protein interactions, five of which were tested and validated experimentally.
Also as part of the process, the team identified proteins that could help treat or slow the disease’s progression. While 28 protein-to-protein interactions they identified are already utilized in 147 different FDA-approved drugs, they also zeroed in on five drugs that — given their expression profiles in the interactome — could be repurposed for mesothelioma therapy.
These include the urinary tract infection drug trimethoprim (branded as Primsol), the malaria drug primaquine phosphate (branded as Primaquine) and the prostate tumor medication cabazitaxel (branded as Jevtana).
The interactome could pave the way for all kinds of mesothelioma therapies, given its “high translational impact” and ability to show how malignant mesothelioma-associated genes “are functionally linked, leading to clinically translatable results,” the team noted.
According to a note on the interactome website, the team plans to update the database supporting the model on a monthly basis to incorporate recently assembled annotations of proteins. They added that the model will allow any registered user to contribute information on unmapped protein-to-protein interactions, much like Wikipedia.