Unraveling a complex disease with a simple blood draw

Blood tests are routine and simple ways to diagnose a number of medical conditions, but until recently, such simplicity hasn’t applied to a complex disease like cancer. 

Researchers and clinicians at MD Anderson are studying and implementing uses for liquid biopsies – blood tests that detect telltale proteins in the blood that signal the presence of cancer. Liquid biopsies may one day lead to catching cancer early, when it’s easiest to treat. 

Take melanoma for example. Anthony Lucci, M.D., professor of Breast Surgical Oncology and Surgical Oncology, is known for his work in using circulating tumor cells (CTCs) to detect early-stage breast cancer. CTCs are primary tumor cells that have shed into the blood or lymphatic system and can lead to additional tumor growth or metastasis. 

Lucci led the first and largest study in this field, with results published in Lancet Oncology back in 2012. Since then, he has discovered that the same CTCs found in breast cancer patients also are present in melanoma. In November, he presented finding that revealed a connection between CTCs and relapse in stage IV melanoma patients. This discovery points to liquid biopsy’s potential to predict which patients have a high risk of disease progression. 

“Optimal management of stage IV melanoma patients remains a challenge since – in spite of promising emerging therapies – many patients develop disease resistance,” says Lucci. “This study, designed to determine if CTCs are associated with relapse, detected CTCs in approximately 40% of advanced-stage melanoma patients.” 

Lucci’s group also is studying the significance of CTCs in earlier stages of melanoma, and hopes to have data available in 2018. 

CTCs are just one type of liquid biopsy being studied at MD Anderson. Others include work with: 

• Cell-free tumor DNA (ctDNA) – derived from dying tumor cells that release small pieces of DNA into the bloodstream or other body fluids 
• Blood plasma – including proteins, antibodies and metabolites 
• Exosomes – tiny virus-sized particles released by cancer cells that contain DNA, RNA and other proteins 

In the past year, MD Anderson entered into a multi-year collaboration with Guardant Health, a major player in liquid biopsy development. The partnership tailors Guardant’s technology to fit MD Anderson’s patient population.

MD Anderson is working closely with Guardant to expand a highly specialized CLIA-accredited lab (CLIA labs comply with federal standards known as the Clinical Laboratory Improvement Amendments that regulate all clinical laboratory testing on humans), and pre-CLIA labs, where Guardant’s digital sequencing technology will be used to create disease-specific assays that will be transferred for use in the CLIA-accredited lab to help detect cancers early and guide treatment.

“Liquid biopsies are far less invasive than traditional biopsies. This benefits our patients and provides significantly enhanced analysis of samples,” says Stanley Hamilton, M.D., who heads MD Anderson’s Pathology and Laboratory Medicine division and the clinical lab component of the Guardant collaboration.

Other leaders of MD Anderson’s liquid biopsy efforts include:

• Scott Kopetz, M.D., Ph.D., associate professor of GI Medical Oncology, is studying tiny traces of cancer called minimal residual disease (MRD) to guide treatment of colorectal cancer, as well as monitoring MRD to assess disease recurrence.
• Ignacio Wistuba, M.D., chair of Translational Molecular Pathology, and Raja Luthra, Ph.D., professor of Hematopathology, are working on pre-CLIA development of liquid biopsy approaches to streamline their transfer to the CLIA lab for potential use for multiple cancers.
• Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention, heads a five-year multi-institutional study launched three years ago to develop a liquid biopsy for the early detection of lung cancer. His study, which uses blood plasma components, involves taking blood samples from up to 30,000 heavy smokers for evaluation.
• Anirban Maitra, M.B.B.S., professor of Translational Molecular Pathology and scientific director of the Sheikh Ahmed Center for Pancreatic Cancer Research, is exploring the link between exosomes and pancreatic cancer. He’s conducted a study to learn how pancreatic cancer patients will respond to particular therapies and what factors are involved in the disease’s recurrence.
• Raghu Kalluri, M.D., Ph.D., chair of Cancer Biology, is studying exosomes and, in particular, a protein encoded by the gene glypican that is present on cancer exosomes. He believes exosomes may have potential as a liquid biopsy for the early detection of pancreatic cancer, as well as a way to deliver therapy.