Milestones magazine: Documenting NCI CCR research since 2017

Every year, the Center for Cancer Research (CCR) makes remarkable contributions to the understanding, detection, treatment and prevention of cancer. 

The CCR scientists and staff publish approximately 2,000 scientific papers per year, run more than 200 clinical trials and care for hundreds of cancer patients in the National Institutes of Health Clinical Research Center. Each published study and clinical trial is a step forward on our journey to alleviate the burden of cancer.

Progress in cancer research often comes in unanticipated areas. As history has shown, it is difficult to predict how an individual discovery will contribute to future progress. Who would have thought that the basic exploration years ago of how the immune system works would one day lead to immunotherapy, one of today’s most promising weapons in the fight against cancer?  It is essential that research institutions create an environment where the unexpected is expected and where new areas of exploration can be freely pursued by its scientists. In CCR, we pride ourselves on our culture of creating an environment where the most important and difficult problems in cancer biology can be fearlessly pursued by our investigators.

In this magazine, we highlight some of the milestones CCR investigators have reached in the last year on the road to mitigating the dire consequences of cancer. The collection of research highlights presented here only scratches the surface of the many advances made by CCR scientists, but they showcase the broad spectrum of our activities and the ingenuity of our scientists. 

Be it groundbreaking methods to visualize the structure of proteins and RNAs that help us understand their function and allow us to design specific drugs, be it the molecular characterization of kidney cancer that will pave the way to new treatment approaches, or be it imaging methods that provide unprecedented precision in detection of prostate cancer, each of these are the result of daring and groundbreaking research that will ultimately benefit cancer patients. 

In a recent conversation I had, CCR was referred to as “a place that changes lives.” The statement could be taken as a mere cliché – but these words are true. All we need to do is watch Travis, seen on the cover, play happily while enrolled in a trial in the NIH Clinical Center for his neurofibromatosis type 1. We make a difference in the lives of our patients and their families. Through our research, we provide cutting-edge treatment, passionate care – and hope.

While our patients’ well-being is the most evident sign of our impact, our clinical successes are built on groundbreaking, innovative laboratory research that identifies new molecular, diagnostic and therapeutic targets and inspires novel treatment strategies. Our basic research program is an engine for new knowledge that drives the development of novel clinical approaches.

This year’s issue of Milestones once again captures the remarkable quality and spectrum of our work in the basic and clinical sciences. In the past year, CCR investigators elucidated a fundamental genetic mechanism in cancer using baker’s yeast; characterized the molecular mechanisms of cancer stem cells; gained insights into how a tumor in one location in the body can prepare a far-flung site for metastasis; and developed novel and improved immunotherapy approaches, to mention just a few of the accomplishments described in this issue. 

The science never stops in the NCI’s Center for Cancer Research. Our labs and clinics bustle with activity at all hours of the day with the singular goal of better understanding, preventing, diagnosing and treating cancer. As a result, in the past year, CCR scientists have published more than 1,300 scientific publications, filed nearly a hundred invention reports and treated thousands of patients in the NIH Clinical Center. This issue of Milestones captures a few select highlights of this year’s research activities.

Featured are achievements in areas where CCR has long been a leader, including immunotherapy, HIV research and cell signaling, but also in important new emerging areas such as big data science and chemical biology, in which CCR is making major investments. Many of the remarkable studies included in this issue represent high-risk projects or long-term endeavors, which CCR is uniquely positioned to undertake in the protected research environment of the intramural program.

It is also reassuring to see that many of this year’s top advances come from our tenure track investigators, highlighting our dedication to training the next generation of cancer researchers. All of the advances summarized here, and indeed all progress in CCR, reflect the work of our dedicated and passionate scientists, clinicians, trainees and administrative staff.

Cancer research is paradoxical in its nature. On the one hand, we see continuous and rapid advances, yet progress is never fast enough, and there is much more to do. That is precisely why the science in CCR never stops. 

We are pleased that in the past year, no fewer than four new clinical approaches developed by CCR physician-scientists were designated as breakthrough therapies by the U.S. Food and Drug Administration, and since 2018, three additional novel therapies were formally approved by the FDA.

The development of these innovative therapeutic strategies is fueled by our broad research program that spans the basic-translational-clinical spectrum as well as by our stable funding. As a result, every year produces a remarkable number of discoveries.

This issue of Milestones features some of the most impactful science conducted in the past year in CCR. These advances include new insights into how genomes are organized and how DNA and RNA function in cells, how cellular processes and signaling events function in healthy cells and how they are affected in cancer. Other major discoveries this year include how cancers become metastatic and what drives the proliferation of cancer cells.

As highlighted on the cover, this year has also deepened our appreciation of the extraordinarily heterogeneous nature of tumors and of individual cells. We have developed important new tools, including artificial intelligence approaches for diagnosis, clever chemical probes to investigate the metabolic changes in cancer and new clinical approaches to help fill unmet needs of patients who have had very limited treatment options. 

2020 was certainly a year to remember. It will leave us with a lasting impression of a historic pandemic that dramatically and painfully upended our lives. The past year also shone a spotlight on longstanding racial inequities and brought polarizing political tensions and unrest.

But we will also remember the past year for the good: for standing together in times of crisis, for appreciating our daily lives and the small things in them, and for pulling together in our communities, none more impressive than how the scientific community worked across disciplines and national borders to tackle COVID-19.

It is those uplifting memories that guided our image selection of CCR staff and our science advances on the cover of this issue of Milestones. They illustrate the new ways in which we come together to get things done.

In CCR, we will also be able to look back at yet another year of outstanding science. In this issue of Milestones, we feature some of the major recent advances made by our scientists and clinicians.

Our basic discoveries form the foundation of our translational and clinical activities, and this year included the development of new computational tools to identify viruses in cancer genomes and the elucidation of the consequences of DNA damage. We learned how to use RNAs as molecular switches and how the RAS oncogene picks its protein interaction partners.

We also advanced our translational science by finding new ways to predict treatment outcomes in immunotherapy by reprogramming immune cells to better fight cancer and, as part of a growing effort in CCR, by identifying the molecular basis for ethnic health disparities in lung cancer.

We developed novel diagnostic tools, one to detect liver cancer using viral exposure history, another to precisely detect prostate cancer using sophisticated imaging technology. And following CCR’s vision of “creating the medicines of tomorrow,” we can offer new treatment options for patients with lymphoma, neurofibromatosis type 1 and Kaposi sarcoma, the latter two leading to approvals from the Food and Drug Administration.

This year has tested our resolve. What has become clear is that science is here to help, be it with a viral pandemic, environmental threats or cancer. Our science gives us hope and it creates solutions — it makes our lives better.

Just as explorers have used maps for centuries, cancer researchers rely on them daily. We use gene maps to identify new cancer drivers, chart cancer pathways and visualize complex gene expression profiles. We also create three-dimensional maps of tumors to target them with radiation, and we increasingly map the complex spatial and functional heterogeneity of tumors at the single-cell level.

The cover of this issue of Milestones stands symbolically for the many uses of various types of maps in cancer research. But it is more than a symbol. This map of Baltimore records differences in geographical distributions of social vulnerability, which includes cancer. It dramatically highlights the pressing issue of health disparities. Differences in cancer outcomes vary widely in local and global populations based on complicated socioeconomic factors, race/ethnicity and geographic location. While access to care is a primary cause for health disparities in cancer outcomes, scientists are discovering that other factors, including the environment and disease predispositions, contribute as well. Eliminating disparities in cancer treatment and care is a major goal in CCR.

It is essential that research institutions create an environment where the unexpected is expected and where new areas of exploration can be freely pursued by its scientists.

Tom Misteli, 
Director of the Center for Cancer Research   

One example of our recent efforts in this area is a study into the molecular foundation of health disparities in prostate cancer featured in this issue of Milestones, which every year highlights some of the most creative, innovative and impactful work of CCR researchers.

Despite the challenges of an ongoing global viral pandemic, activities at CCR have continued unabated. Our advances in the past year cover a broad range of cutting-edge topics in cancer research, including progress in basic studies on how genomes protect themselves from damage and new insights into how tumor growth is affected by the host tissue, by the bacterial microbiome of a patient and the age of a patient. We have also made major progress in precision medicine by inventing new ways to accurately diagnose cancers, optimize therapy options for patients and predict treatment responses.

Our ultimate goal remains the development of new treatment options for patients and expanding the representation of patients in our clinical trials. These efforts culminated in the past year in the approval by the U.S. Food and Drug Administration of no fewer than four new drugs developed by CCR researchers. In addition, clever new clinical and surgical technology and new ways to harness the immune system for cancer therapy bring new options and hope to patients.

Maps help guide and chart our discoveries in cancer research, but even the best maps cannot predict what is ahead. Discovery inherently contains an element of serendipity and adventure. At CCR, we fully embrace the challenges and the opportunities of the unknown as we continue to explore paths towards ending cancer as we know it.