Where Cancer Goes, We Follow
"Disruptors" is a series sharing new and innovative ideas and viewpoints from Columbia Cancer researchers and clinicians that challenge conventional thinking about cancer care, research, and beyond.
Cancer remains a leading health issue worldwide, and its burden continues to increase with the growth and aging of the population. While progress in our understanding, diagnosis, and treatment of cancer has been tremendous, the quest for innovation that will get us closer to a cure continues. Not surprisingly, engineers started to enter the field of cancer, to help provide models for studying this hugely complex disease under controlled conditions.
One major challenge to developing effective treatments is that the progression of cancer cells, the rate of invasion, their ability to evade the immune system, and their response to treatment are all unpredictable and change from one patient to another. A notable example is breast cancer where there is no way to tell which patients will develop metastasis, information that is critical for early administration of the right therapy. Because animal models largely fail to mimic the complexity of metastatic disease progression or to predict therapeutic efficacy in humans, there is a long-standing need for “better” models of human cancers.
For a very long time, cancer and engineering have developed on completely separate paths. The word “engineer” comes from the Latin roots: ingeniare, which means to devise and invent, and ingenious, which means clever. As engineers, we see ourselves as problem-solvers, within limitations imposed by practicality, safety, and cost. Since ancient times, engineers have designed materials, structures, machines, and systems supporting many of society’s needs.
More recently, the advances in biology, medicine, and engineering converged into the field of tissue engineering, to repair and replace human tissues lost to injury or disease. The concept of tissue engineering is very simple: we enable the cells to perform their normal function outside the body by providing environments that resemble those during normal tissue development and regeneration.
Engineers and Cancer Scientists Together Study 'Cancer Patient on a Chip'
Initially driven only by the needs of regenerative medicine, tissue engineering also extended to the “organs on a chip” in vitro platforms where micro-sized human tissues are linked into physiological units, designed to study a disease or test drug safety and effectiveness. Picture a device the size of a credit card with millimeter-sized human tissues of different kinds: liver, bone, lung, bone marrow, tumor. Each of these tiny tissues that are placed into this tiny device is designed to recapitulate a function of a specific organ (such as metabolism in liver or hematopoiesis in bone marrow), hence the name “organs on a chip.”
In cancer research, we use these devices to connect the tumor with its metastatic sites so that we can model how the cancer spreads and evaluate the effects of certain drugs and cell treatments on human organs. Because all tissues can be made starting from small samples of a patient’s own cells, “organs on a chip” can be used to study cancer progression and response to treatment in different people.
A Miniaturized, Personalized Approach
The National Cancer Institute’s Physical Sciences in Oncology program was established to support the development of tissue-engineered technologies for cancer research through collaborative projects that engage the fields of medicine and bioengineering. Here at Columbia, within this program, we are modeling how triple negative breast cancer spreads into other organs. Using an “organs on a chip” platform, the tumor is physiologically connected by vascular flow with its potential metastatic sites (lung, liver, bone) and the heart muscle, a tissue that is protected from metastatic invasion. We are collaborating with leading systems biologists, oncologists, and pathologists to detect the mechanisms of tumor progression and drug resistance, and help develop effective, patient-specific treatments.
In another collaborative project, we are working on a metastatic model of prostate carcinoma. Given the critical importance of bone metastasis in the progression of prostate cancer, our goal is to create a metastasis model providing a platform for drug discovery and personalized medicine. We are also using our “bone marrow on a chip” as a niche for primary leukemia cells, to build patient-specific models of leukemia. Again, our goal is to accelerate the identification of clinically relevant drug targets and personalized therapeutics for the treatment of blood-related cancers.
Looking forward, our miniaturized, personalized approach to studying cancer, one patient at a time, could reduce the current trial-and-error approach to treatment, through better understanding of how a normal cell turns into a cancer cell, and why some people respond to treatments while others do not. Grand challenges call for fresh and disruptive approaches, and these are often found at the intersections of disciplines. I expect that engineers, working with cancer scientists and clinicians, will help us meet one of the greatest needs in medicine of our time: curing cancer.
Gordana Vunjak-Novakovic, PhD, is University Professor, Mikati Foundation Professor of Biomedical Engineering and Medicine, and Professor of Dental Medicine at Columbia University. She is a member of the Herbert Irving Comprehensive Cancer Center and focuses on engineering human tissues for regenerative medicine, stem cell research, and modeling of disease.