Resources from the Frederick National Laboratory for Cancer Research

August 3, 2023, by NCI Director Dr. Monica Bertagnolli

In 1985, NCI launched a human cell line panel, known as the NCI-60, with the aim of improving the discovery of new cancer drugs. The cell line panel “was a controversial departure, born of frustration with previous efforts,” wrote Bruce A. Chabner, M.D., in 2016 in the Journal of the National Cancer Institute. 

“The concept of incorporating the diversity of human cancers into a cell line screen set the stage for extraordinary advances in targeted drug development,” wrote Dr. Chabner, who, at the time the NCI-60 was created, was an NCI investigator whose long-standing efforts led to the development of the drug paclitaxel (Taxol), and contributed to the development of several other chemotherapies.  

Among the samples screened by the NCI-60 was the extract of the sea sponge Halichondria sp., found off the coast of Japan. The NCI-60 showed its potent anticancer activity and presumptive mechanism of action, which ultimately led to the chemotherapy drug eribulin mesylate (Halaven) primarily to treat metastatic breast cancer. 

 Today, the NCI-60, which remains available to the research community free of charge, is maintained by staff members from the Frederick National Laboratory for Cancer Research (FNLCR). The NCI-60’s story—making an innovation broadly available—is illustrative of some of the ways FNLCR supports cancer science by developing and offering tools and resources to propel research progress. 

The facility, which is among 42 Federally Funded Research and Development Centers in the United States, is owned by the government and operated by a private sector organization. It was renamed a national laboratory in 2012, one of just 18. As NCI Principal Deputy Director Doug Lowy, M.D., pointed out in a recent Cancer Currents blog post, FNLCR “maintains more than 15 million biological specimens, frozen tumor samples, research reagents, and genetically engineered mouse models of human cancers.”  

These tools, as Dr. Lowy noted, are often the foundation upon which NCI, other NIH institutes, and the broader scientific community build groundbreaking research.  

Consider three recent examples: 

The NCI Patient-Derived Models Repository, operated by FNLCR, is a national repository comprised of patient-derived xenografts (PDXs), which are created by taking a sample of a patient’s tumor and grafting it into a mouse. The models include over 300 in vitro patient-derived tumor cell cultures (PDCs) and almost 370 cancer-associated fibroblasts (CAFs), as well as around 300 patient-derived organoids (PDOrg).  

 These models are available nationally to academic investigators and public–private partnerships for drug discovery–related research at extremely modest cost. Notably, they emphasize underrepresented model types, such as rare cancers and those representing racial and ethnic minority populations. Many studies document that these models greatly improve the capacity to mimic a patient’s response to treatment. 

The National Cryo-Electron Microscopy Facility at FNLCR helps lead the adoption of the technique once dubbed the “method of the year” by Nature Methods. Capable of determining the structure of biomolecules at atomic resolution, the cryo-EM lab houses complex instrumentation, in addition to scientists with deep expertise in the computational methods required to extract the best results from this burgeoning technology. Data generated by cryo-EM can be of high-enough resolution to generate atomic models for proteins and other biological macromolecules. To date, the cryo-EM laboratory’s data contributions have been acknowledged in 103 scientific publications. Cancer researchers can apply to submit samples for analysis and are responsible for no costs apart from shipping. 

The demand for cryo-EM experiments is greater than the workforce trained in its techniques. FNLCR is at work there, too. Last year, FNLCR conducted a first-of-its-kind 5-day workshop in cryo-EM grid preparation, screening and data collection, data processing, and model building and validation, open to scientists from across the United States.  

When the RAS Initiative was proposed in 2012, efforts to target mutant proteins of the RAS oncogene for therapeutic benefit were, for all practical purposes, stalled. The RAS oncogene is implicated in up to 30% of all human cancers, and cancers driven by this oncogene are often resistant to current treatments. The conventional wisdom at the time the initiative was launched was that cancers precipitated by mutant RAS proteins were undruggable because the protein products lacked bindable pockets. 

To place newfound emphasis on this vexing issue, NCI requested that FNLCR be the coordinating center of new RAS-related initiatives conducted at NCI laboratories, external NCI-funded institutions, biotechnology firms, and pharmaceutical companies. Scientists working on protein production, assay development, and structural discoveries joined the effort. 

In addition to a coordinating role, which includes a biennial symposium that drew close to 800 virtual and in-person attendees in 2022, FNLCR developed unique reagents that it distributes widely to the research community at modest cost. To date, these reagents have been supplied to 623 institutions in 43 states and 45 countries. 

These efforts to rejuvenate RAS research are clearly demonstrating progress. In 2021, the Food and Drug Administration granted accelerated approval to the first KRAS-blocking drug, with the approval of a second drug coming about a year later. Several other KRAS inhibitors are currently being tested in clinical trials and a number of others are in preclinical development. Researchers are also using what has been learned about RAS biology to find ways to indirectly target its activity and to address RAS-directed therapy resistance.  

These examples showcase only some of the resources available from FNLCR. The lab is a national resource and facilitator of research in areas of pressing national need, including cancer, AIDS, and other infectious diseases.  

As made clear by the National Cancer Plan, government alone will not have all the answers, nor will industry or academia. It will take everyone to end cancer as we know it, and FNLCR stands ready to serve the entire research community. 

To access the lab’s resources, visit the FNLCR website.  

The bottom line: FNLCR is a rich scientific resource available to researchers around the world working to deliver discoveries that benefit people with cancer and those at risk for the disease.