New cancer drug targets emerge from massive protein analysis

Researchers at Baylor College of Medicine scoured all of the proteins present in 500 diverse cancers and made a surprising discovery: All of those cancers, it turns out, can be slotted into 10 subtypes. Each subtype is driven by a common set of proteins.

The discovery, reported in the journal Nature Communications, could inspire the development of new drugs or improved treatment strategies, argued co-author Chad Creighton, Ph.D., associate professor of medicine and co-director of cancer bioinformatics at Baylor’s Dan L. Duncan Comprehensive Cancer Center.   

"Interestingly, four of these 10 subtypes actually do not involve the cancer cells themselves,” Creighton said in a statement. “They represent differences in the tumor microenvironment, the cells and tissues that surround the tumor, and these subtypes are very distinct from each other."

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Usually, molecular profiling of cancer is done by examining mRNA, which is responsible for protein synthesis. But proteins can change after they’re made, so researchers who just examine mRNA could end up missing important cancer pathways, Creighton said.

Using data from the Clinical Proteomic Tumor Analysis Consortium, Creighton and colleagues analyzed ovarian, breast, colon, renal and uterine cancers. They found some interesting characteristics of the four subtypes that didn’t involve cancer cells. Two of them were characterized by immune components like cancer-killing T cells, for example.

The Baylor team also discovered three cancer subtypes that hadn’t emerged from previous mRNA analyses. One involved a part of the cell called the Golgi, which had previously been linked to the transformation of cells into malignancies. Another subtype, which was found exclusively in renal cancer, was linked to a boost in hemoglobin.

The role of proteins in cancer is a topic of increasing interest among oncology researchers. Baylor was a participant in another study earlier this year led by Pacific Northwest National Laboratory that examined 8,000 proteins involved in colon cancer. That study uncovered new insights into how enzymes related to metabolism and programmed cell death play an important role in driving colon cancer.

The new Baylor study describing the 10 cancer subtypes is available for free online and includes statistics for all of the proteins the researchers identified. They also added their data sets to UALCAN, an interactive portal researchers around the world can use to analyze cancer data.

“These proteome-based subtypes provide a framework for examining pathways or processes that, at the protein level, would cut across individual cancer types,” the authors wrote in the study.