What are the big unanswered questions about cancer? We asked the experts.

Over the 40-year history of the University of Colorado Cancer Center, its investigators have answered many questions about cancer – what causes it, how to prevent it, and how to treat it. Those discoveries have helped many people with cancer live longer, better lives.

But the quest to solve cancer’s mysteries goes on. And as we look forward to the CU Cancer Center’s next 40 years and beyond, we asked several of our top minds a simple question:

What is one big unanswered question about cancer?

Here are their answers. 

Manali Kamdar, MD – associate professor of medicine in the CU Anschutz Division of Hematology and clinical director of lymphoma services:

One of the biggest unanswered questions in cancer is how we can move toward truly chemotherapy-free, immune-based treatments – and make sure these advances aren’t limited to a select few. It’s not just about achieving long-lasting remissions through the immune system, but also about making these breakthroughs accessible and equitable for every patient, no matter where they live or what resources they have.

Christopher Lieu, MD –professor of medicine in the CU Anschutz Division of Medical Oncology and CU Cancer Center associate director for clinical research:

Despite the success of immunotherapies in several cancers, one of the biggest remaining mysteries is how to effectively turn “cold” tumors “hot” in diseases like colorectal cancer and pancreatic cancer. Many solid tumors create an extremely hostile and immune-suppressive local microenvironment, essentially building a fortress that excludes or deactivates T-cells. Unraveling the complex signaling networks used by cancer-associated fibroblasts and other stromal cells to maintain this immunosuppression is essential to making checkpoint inhibitors and other immunotherapies work for a majority of patients.

D. Ross Camidge, MD, PhD -- professor of medicine in the Division of Medical Oncology and CU Cancer Center director of thoracic oncology:

Why do people die from cancer? It’s usually not to do with mass effect interfering with organ function (although sometimes), as you can have the same burden of a sarcoma and be asymptomatic. And another: Why don’t we pay basic scientists as if our lives depended on it?

Cathy Bradley, PhD – dean of the Colorado School of Public Health and CU Cancer Center deputy director:

Our understanding of risk of developing cancer if a lesion is identified and risk of cancer recurrence if a lesion is removed is nascent. We overtreat many people and undertreat others – at great expense and diminished quality of life.

James Degregori, PhD – professor of biochemistry and molecular genetics and CU Cancer Center deputy director:

How do we better understand, both through experimental and epidemiological methods, how a person’s age interacts with exposures (from smoking to infections) and lifestyles (from exercise to diet to stress) to determine the risks of cancer occurrence and pathogenicity? Aging influences the trajectories of cancer from initiation, metastatic spread, to therapeutic outcomes, as do exposures and lifestyles. But there has been insufficient study for how aging interacts with exposures and lifestyles to alter these trajectories.

Virginia Borges, MD – professor of medicine in the Division of Medical Oncology and deputy division head:

Why are we seeing more cancers in young people? Young women’s breast cancer is increasing faster and we are seeing more 20-year-olds being diagnosed than before. It is not known why this is happening. 

Kyle Concannon, MD -- assistant professor of medicine in the Division of Medical Oncology:

Why me? We say that many people develop cancer because of “bad luck.” My interpretation of “bad luck” is that we just don’t know.

Natalie Serkova, MD – professor in the Department of Radiology and CU Cancer Center associate director of shared resources:

Why can’t we develop a preventive screening for any cancer? In the future, could that be a “whole body mammography” screening for any cancer? Or a genetic test in a tube for predicting any cancer?

Hatim Sabaawy, MD, PhD, MS – professor of medicine in the Division of Medical Oncology and CU Cancer Center associate director of translational research:

At our CU Cancer Center’s 40^th anniversary, I ask: When will cancer-related death be eliminated? I note, not asking for a cure! With recent strides towards cancer cure, early stages, testicular cancer, and minority responders of targeted and immunotherapies, cure is otherwise an exception. A number of seismic changes at the policy, society, academic, and industry levels are necessary; principally a renewed moon shot or another (inter)national cancer act to transform prevention, interception, diagnosis, and treatment of cancer. To meet the challenges of the thousands of cancer subtypes rather than their anatomical sites, expanding knowledge and data on longitudinal cancer clonal evolution and applying more innovative and ultraprecision approaches at various elements of cancer care hold the keys for a better future. These may include precision diagnostics with liquid biopsies and wearable or implanted sensors, identifying multiomic vulnerabilities within each cancer during routine checkup with blood tests and screens, precision surgeries with live cell imaging leaving no cancer cells behind, precision multimodality therapies for targeting each patient’s cancer from multiple therapeutic angles simultaneously to overcome, reduce, and eliminate resistant and/or persistent cancer cells, precision maintenance for suppressing evolving cell states and cancer plasticity through dynamic monitoring, and precision consolidation at relapse with personalized clonally targeted therapies for preventing metastasis. When these changes and advances in cancer care prevail, we could see cancer as a manageable chronic disease; I dream, in my lifetime.