Grouping Cancer by Molecular Pathways Could Improve Diagnosis, Treatment

Many neuroendocrine cancers may be misdiagnosed without molecular pathway mapping.

Understanding which factors contribute to cancer growth can result in markedly improved ways to diagnose and treat the disease. Researchers used a newly developed approach that analyzes molecular pathways to group 10,000 cancers of 32 types into 10 different classes in hopes of improving treatment, according to a study published by Clinical Cancer Research.

“When we study cancer at the molecular level we realize that there is not a single pathway or process that drives all the different types of cancer,” said first author Chad Creighton, PhD.

Previous studies have examined individual types of cancer in detail. The authors noted that lung cancer has been subtyped to represent different molecular pathways that drive tumor growth.

“In this study, we wanted to find common pathways across cancers from different tissues,” Dr Creighton said.

To do so, the researchers analyzed data included in the Cancer Genome Atlas for 10,000 human cancers. A computational approach was used to account for tissue-specific differences and determine which pathways remained. The authors then placed the cancers into 10 major groups.

A majority of the classes include cancers of different tissues with a common molecular pathway that have been altered and may promote cancer growth, according to the study.

The authors also identified genes involved with each of the classes to determine the overall action of the pathway.

“We found a class that had a very high expression of altered genes that are involved in the immune checkpoint, which refers to tumor molecules that signal the immune cells in charge of destroying the tumor to leave it alone,” Dr Creighton said. “Other classes had altered genes in pathways linked to metabolism or stress."

Another group was observed to have a molecular signature of neuroendocrine tumors, which have their own unique profiles, according to the study.

“We expected that about 1% of the tumors would show a neuroendocrine signature, but we found that about 4% were showing this,” Dr Creighton said. “This represents a substantial number of patients when you consider all human cancers.”

Notably, the authors said that the original diagnosis for the disease was not neuroendocrine cancer, despite having the molecular signature. These results suggest that there are multiple missed cases of neuroendocrine cancers, which may impact treatment, according to the study.

“We think there is a need for reconsidering what type of markers to look for to identify neuroendocrine tumors,” Dr Creighton said.

The authors noted that grouping cancers in this way may help develop a more targeted therapy for certain diseases.

“An appreciable number of human cancers manifest these pathways that we found to be relevant in the laboratory setting,” Dr Creighton said. “We think it is very important to map out the pathways a cancer seems to be using to grow. Knowing this can be the first step in determining how to better target that particular cancer.”