Published in the newest issue of Science Signaling, an article from the laboratory of Eric B. Haura, MD, written by lead author Matthew A. Smith, PhD, MSPH, and colleagues, describes how a proximity ligation assay (PLA) can be used to analyze biological processes deep within lung cancer tumors.
“Our lab is developing additional assays reflecting protein complexes relevant to cancer therapeutics and we envision the ability to use these assays to help make therapeutic decisions for our patients,” stated Dr. Haura in a news release. The study, “Annotation of Human Cancers with EGFR Signaling–associated Protein Complexes Using Proximity Ligation Assays,” applied PLA to a new setting of cancer diagnoses to determine the classes of signaling events occurring within tumors and suggest treatment options based on their relevance to any identified pathways.
“We think this is an exciting new way to look at targetable signaling activity in cancer cells,” said Dr. Smith. “If we can figure out which molecular pathways are activated, we will be better able to match patients to available targeted therapies and hopefully improve outcomes.”
The PLA technique involves protein complexes, rather than single proteins or genetic mutations, as biomarkers for cancer. Complexes are more relevant than single entities due to the nature of proteins to interact with many other proteins instead of functioning alone. Using protein complex biomarkers may increase the accuracy of describing cellular activity within tumors.
So far, the team has investigated epidermal growth factor receptor (EGFR) signaling in the context of PLA. This protein was selected due to the tendency of cancer patients, especially non-small lung cancer patients, to express high levels of mutated EGFR. “We show that it is feasible to build assays that reflect protein complexes in cancer cells, and these assays are associated with drug sensitivity,” said Dr. Haura. As such, another application of PLA is determining mechanisms of drug resistance that make some lung cancer cases difficult, to fully resolve.
If Moffitt Cancer Center continues to pursue developing PLA for diagnosis lung cancer, a new test may be added to its cohort of lung cancer screens. Screenings include high-definition CT scans that can highlight tumor-like growths requiring further evaluation to determine the possibility of and diagnose lung cancer.