A potential diagnostic for pancreatic cancer

Now, however, Tony Hu, a researcher in the Biodesign Virginia G. Piper Center for Personalised Diagnostics and his colleagues have devised a crafty method to identify pancreatic cancer early in its development. Their technique relies on the sensitive detection of extracellular vesicles (EVs)—tiny bubbles of material emitted from most living cells.

In new research appearing in the advanced online issue of the journal Nature Biomedical Engineering, Dr. Hu and his colleagues describe a method to detect EVs derived from tumors that carry a particular surface protein that functions as a telltale marker for pancreatic cancer. The ability to accurately detect this protein, known as EphA2 may allow it to serve as a signpost that could diagnose even the earliest stages of pancreatic cancer.

"Pancreatic cancer is one type of cancer we desperately need an early blood biomarker for," Hu says. Currently, the only cure for pancreatic cancer remains surgical removal of diseased tissue but in many cases, this is not feasible due to the degree of cancer spread at the time of diagnosis.

"Other technology has been used for detection, but it doesn't work very well because of the nature of this cancer. It's really hard to capture an early diagnostic signal when there are no symptoms. It's not like breast cancer, where you may feel pain and you can easily check for an abnormal growth."

This research now demonstrates that a platform that uses the interaction between two different nanoparticles to detect tumor-associated EV's can keenly discriminate between blood samples from patients with pancreatic cancer, pancreatitis—a disease that can share symptoms with pancreatic cancer—and healthy subjects. Further, this technique may ultimately be useful for the rapid and sensitive detection of a range of diseases, based on their unique EV signatures.

EVs are released by both eukaryotic cells (including human cells) and prokaryotic cells, (like bacterial cells, which lack a nucleus or other membrane-bound components). EVs resemble miniature versions of the cells which produce them, though they lack much of the cell's complex machinery.

There are a variety EV types, which develop from their parent cells in different ways. The current study examines a class of EVs known as exosomes, which range in size from 50-150 nm. Exosomes are derived from membrane-bound compartments within the cell (known as endosomes) that eventually fuse with the cell's outer membrane to liberate exosomes into the extracellular space.

Once thought to be mere debris from the cell's metabolic activities, EVs are now recognised as vital components with far-flung responsibilities that are only beginning to come to light. EVs form a subtle and sophisticated communications network operating between cells and are highly conserved across species, suggesting their essential role in life processes.

Among their activities are the transfer of nucleic acids, proteins and lipids which may trigger physiological and pathological changes, both in parent and target cells. EVs also play crucial roles in innate and adaptive immune responses.

Research has shown that circulating EVs are significantly elevated in a number of diseases. EV's appear to play an important part in the development and progression of certain cancers, including pancreatic cancer.

One apparent function of tumor-derived EVs, once they exit their parent cell, is to migrate to other tissues and modify their surroundings to create an environment (niche) favorable for tumor invasion and growth (metastasis).

Like pioneers on a new continent, EVs can thus pave the way for cancer cells to follow in their wake. There is also evidence that tumor-derived exosomes can help tumor cells develop drug resistance by exporting anti-tumor drugs or neutralising antibody-based drugs.

EV's may serve as a useful means of evaluating cancer burden and response to treatment, since levels of tumor-derived EV's in patient blood samples should increase with tumor mass and decrease upon favorable response to cancer therapies, and thus offer a rapid, inexpensive and non-surgical means to examine the changes in the state of a patient's disease.

Identification of tumor-associated EV proteins, such as EphA2, and better understanding of the role of EV's in tumor development and metastasis may thus open a new chapter in cancer diagnosis and treatment monitoring.

Given that pancreatic cancer cases are often characterised by high rates of therapy resistance, improved treatment monitoring is urgently needed so that personalised treatments can be quickly modified to improve individual patient outcomes.

Further, better understanding of the specific factors that control EV actions to promote cancer development and metastasis may lead to the discovery of new mechanistic targets for cancer treatments that allow custom-tailored therapeutic treatments.