The search for valuable cancer-related proteins

MD Anderson’s proteomics platform provides a valuable institutional resource, complete with state-of-the-art instruments and specialized expertise to help researchers analyze and understand thousands of cancer-related proteins. These proteins may be useful as therapeutic targets, early detection signals or biomarkers of cancer treatment response for a number of disease types, including lung, colon, breast, ovarian, pancreatic, prostate, gastric and leukemia.

The platform is one of 10 research engines powering MD Anderson’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives.

Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention and leader of the proteomics platform, spoke with Cancer Frontline about the work of the platform and its role in elevating the Moon Shots Program.

Q: Can you describe proteomics as it relates to cancer biology?

A: Proteins are the functional component encoded in the genome that are involved in virtually all aspects of cancer, from tumor development to progression and metastasis. Much emphasis in the cancer field has been on the genome and genetic mutations that lead to cancer. However the effect of such mutations occurs directly at the protein level.

Although they are encoded in the genome, proteins are highly dynamic. They are affected by so many external factors and stimuli that may not be predicted directly at the genome level. Hence the interest and the need to directly interrogate proteins for their association with altered states such as cancer.

We rely heavily on mass spectrometers to dig deep into blood and tumor cells to find novel features that aid in diagnostics and treatment. From one drop of blood we can get enough data to fill a laptop computer, and we use those data to develop early detection and treatment approaches that improve the lives of our patients.

Q: What is the role of the proteomics platform in supporting the Moon Shots Program?

A: The platform does in-depth analysis of biological fluids, tumor cells and tissues to find proteins that can be used as targets for diagnostic or therapeutic applications. In our work, we collaborate closely with several of the Moon Shot™ teams to analyze a variety of cancer types, including lung, colon, breast, ovarian, pancreatic, prostate, gastric and leukemia.

We’ve illuminated several features of cancer through the platform’s work, such how cancer cells transition from one state to another, more metastatic state, and how we can better predict risk of developing lung cancer.

As another example, we’re now working closely with the Prostate Cancer Moon Shot™ team to profile blood proteins and metabolites to determine risk of prostate cancer progression among subjects under active surveillance for prostate cancer.

Q: Together with the Lung Cancer Moon Shot™, the platform has initiated a major lung cancer screening trial. Can you share a bit about the goals of that trial?

A: As a result of platform discoveries, we launched this major trial with the Lung Cancer Moon Shot to improve lung cancer screening and early detection. There are two components to the trial.

First, we aim to improve the interpretation of indeterminate nodules that are often found among subjects that undergo computed tomography (CT) screening for lung cancer. In many cases, the CT scan is not able to provide a clear answer as to whether a nodule is cancerous or not. We hope that our blood test will be able to clarify those unclear results without further invasive follow-up tests.

Secondly, we plan to determine the need for CT screening among subjects that currently do not meet screening criteria based on their smoking history. In fact, the majority of individuals that are destined to be diagnosed with lung cancer do not meet screening criteria. Therefore, if we can better determine cancer risk through a simple blood test, we could have substantial impact on lung cancer mortality.

Q: How has that trial progressed so far?

A: We have obtained proof of principle through a blinded validation study that a blood test would outperform risk criteria based on smoking history. At present we are doing additional validation with independent cohorts to further confirm the findings and ultimately obtain approval for the test from the Food and Drug Administration.

Q: What other projects are on the horizon for the platform?

A: We actively are working to take advantage of advances in technologies to improve our abilities to study cancer-related proteins at higher and higher resolutions. We will continue to identify novel molecular features of cancer that contribute to improved risk assessment. We have active projects in this area at work with the Breast Cancer Moon Shot™ and Pancreatic Cancer Moon Shot™. Further, we are performing in-depth investigations of novel therapeutic targets we have identified to develop new immunotherapeutic approaches to treat a variety of cancers. We are excited to see these projects move forward to advances for our patients in the clinic.

Q: How has the Moon Shots Program enabled your work?

A: The platform brought together proteomics experts from both academic research centers and biotechnology in a way that hadn’t been done elsewhere previously. This was made possible by the Moon Shots Program, and makes this expertise available to Moon Shots researchers when it wouldn’t normally be found in a cancer center.

By working in close proximity to these colleagues across MD Anderson and the Moon Shots Program, we are able to analyze samples from their patients and laboratories more quickly and identify protein targets more efficiently. Our synergy with the other Moon Shots platforms also helps to enhance the value of the data, as we all work together toward our common goal of ending cancer.