DCTD Programs
In this October 2023 Issue:
STAFF HIGHLIGHT: Brian Sorg, PhD
In this edition of the DCTD newsletter, Brian Sorg, PhD, branch chief of the Cancer Diagnosis Program’s (CDP) Diagnostic Biomarkers and Technology Branch (DBTB), describes how he landed in the field of biomedical engineering and the latest in diagnostic technology.
How did you end up becoming a biomedical engineer?
Growing up, I always liked math and science, and biology was my favorite subject in high school. When I got to college, I planned to major in biology, graduate, and find a job; however, I noticed that engineering degrees had really good job prospects. I felt bad leaving biology behind, but I decided to major in electrical engineering. During college I had two summer research jobs in microbiology at the University of Maryland, where I worked in the laboratory of a family friend who was a professor, and partnered with a graduate student who helped me think about my options after college. My professor friend gave me the idea to take an electrical engineering class at Maryland with one of his faculty friends that focused on artificial and biological neural networks. That class really influenced me — I liked being able to combine biology and engineering, so I decided to go to graduate school for a masters’ degree in biomedical engineering.
During my early years of graduate school, I worked in a lab studying the biophysical properties of the motor protein kinesin. I built and used an apparatus called optical tweezers for optical trappings, where you can grab particles with a laser beam and place them on kinesin on microtubules. That work was interesting, but I wanted to do something more clinically applied, so I decided to pursue a PhD in a topic related to biomedical optics. I found programs in Texas that focused on biomedical engineering and biomedical optics that were clinically related, like imaging, ablation, and detection methods that used lasers. I continued in this research area in my post-doctoral years, and I worked on optical measurements of oxygen transport to tissue. My post-doc lab wanted to develop an imaging method to measure tumor oxygenation, so I set up a microscopy system using hyperspectral imaging of hemoglobin saturation in tumor microvasculature. This work satisfied three things that I liked scientifically — pure biology, math and statistics, and engineering. I had access to so much variety in this research, and I was able to constantly move back and forth between each discipline.
After my post-doctoral work, I started my own lab at the University of Florida in biomedical engineering. I liked academia and being directly involved in student growth, but it was hard to be the manager and give up working in the lab. Also, I really liked writing papers on my academic work, but I wasn’t so fond of writing grants. Grant writing was a good experience for me though, because now I can appreciate what grantees experience when they write their grants. At NCI, I work with principal investigators, and I really understand their position.
I’ve been at NCI for 11 years, and all those years with CDP/DBTB. When I joined DBTB, Dr. Jim Tricoli was the branch chief, and there were only two people in the branch. I’ve taken over the branch chief position after Dr. Tricoli’s recent retirement, and we are trying to build up the number of staff in the branch. I was a program director before my role as branch chief, and I still have a grant portfolio because I’d like to stay connected to the science and the grants process considering that our branch has between 150-175 active grants.
What are some highlights from the diagnostics/technology world in the last ten years?
Over the last decade we’ve seen great trends in biosensors, in vitro imaging, and cellular and molecular analysis. Spatial resolution has increased, and various -omics measurements can now be done at the individual cell level. Also, with multiplexing you can visualize multiple kinds and increasing numbers of molecules with increased resolution. Since the technology related to single-cell profiling and imaging has progressed, now we can collect data for the molecular profile plus all the molecules and cell positions relative to each other. So much data are generated, and we need new ways to handle it all. We saw artificial intelligence (AI) entering this research field several years ago, but now it has exploded. AI is everywhere in optics because it is useful to handle vast quantities of data and simplify optical hardware designs. I see CDP grantees interested in using AI as subcomponents of their work. We’re still working through how we can use AI in medicine; there is still a long way to go in the medical field.
What do you see on the horizon in cancer diagnostic research?
Investigators are really interested now in making technology smaller, more efficient, and more affordable. One example is to move technology out of large medical center labs and into the community and make it useable by people who would not usually have specific training. For example, there is interest in integrating technology into smartphones to allow the point-of-care to be at home. This was happening pre-COVID, but the increase in telemedicine due to COVID has accelerated this trend.
Another area that has strong research interest is tissue chips. As a program director in CDP, I was involved with a National Center for Advancing Translational Sciences (NCATS) collaboration. The research focused on developing a model of breast cancer metastasis to the liver. The models involved studying ‘cancer on a chip’ to show how the breast cancer cells behaved clinically: the dormant cells escaped treatment. I’ve also worked with NASA to develop tissue chips, and the pharma industry is interested in using tissue chips through the drug development process. Clinical trials are expensive and time consuming, and early preclinical data from animal models do not always translate to humans. Therefore, it would be helpful to have data using human tissue chips first. One goal of my work with NCATS is to try to propel this field forward by bringing FDA and industry partners together. I am speaking with staff from other DCTD programs about how we might create tissue chip initiatives that are focused on cancer. Toxicity studies might be the easiest thing to do first on a chip because many therapeutic compounds are toxic. It would be powerful to accurately show toxicity of anti-cancer agents early in the research process — this would save time and money.
Dr. Sorg’s research interests and NCI grant portfolio are focused on technology development for biosensors and various cellular and molecular separation and analysis techniques for biomarker discovery and clinical application. His portfolio and research interests also include liquid biopsies, microfluidics, tissue chips, in vitro optical imaging, and other biophotonics technologies for applications in cancer diagnosis and treatment.
SPOTLIGHT: NCI Updates the NCI-60 Human Tumor Cell Lines Screen
NCI has modernized the methodology for the NCI-60 to a high throughput screen, which includes a change from 96-well to 384-well plates. The NCI-60 has been an integral, free research resource for anti-cancer drug discovery and development investigators for more than 30 years, with more than 110,000 total compounds screened in 260,000 assays.
The results of this update include improved operational efficiency and methodology that is now aligned with the standard screening technology being used in the field (e.g., automated high-throughput assay in 384-well plates).
Read more about the NCI-60 and this important methodology update. Email DTP staff with questions: ncidtpinfo@mail.nih.gov.
September 30, 2023 was the last day to submit compounds for testing using the traditional platform. Compounds submitted after this date are being tested in the modernized NCI-60 HTS384 screen.
SPOTLIGHT — NCI National Clinical Trials Network Biospecimen Banks (NCTN Biobanks) Work with Moonshot Projects
The NCTN biobanks are a unique resource for well-annotated biospecimens collected during cancer clinical trials for use in research and for biomarker discovery with a goal to advance cancer treatment.
When individuals with cancer participate in clinical trials, their tumor biospecimens may be analyzed as part of the trial’s research objectives. These biospecimen studies are a critical component of research to advance cancer therapy.
As an integral part of the NCTN, the NCTN Biobanks collect, process, and store well-annotated biospecimens from the NCTN phase 3 and phase 2 trials, and some early phase trials. NCTN biospecimens have associated clinical and outcome data, which enhance the value of this unique resource. The Pathology Investigation and Resources Branch of the Cancer Diagnosis Program manages one pediatric and four adult biobanks, which received NCTN biobanking U24 grants (RFA-CA-20-002).
The demand for well-annotated legacy biospecimens for secondary research studies is steadily increasing in scale and scope. Launched through the Cancer Moonshot and funded by the 21st Century Cures Act, the Moonshot Molecular Profiling to Predict Response to Treatment Initiative (MP2PRT) awarded seven contracts to the COG and NRG NCTN biobanks between 2020-2022. The following five publications describe results stemming from the COG Biobank projects.
| Publication Title/Link to Paper | Highlight |
|---|---|
| Genetic changes associated with relapse in favorable histology Wilms tumor: A Children's Oncology Group AREN03B2 study (Gadd; 2022) | Early and late samples in primary-relapse Wilms tumor pairs had different mutations |
| The following four publications from members of the COG Soft Tissue Sarcoma Committee showcase the importance of well-annotated biospecimens to possible improvements in disease classification, treatment decisions, and outcomes. | |
| TP53 germline pathogenic variant frequency in anaplastic rhabdomyosarcoma: A Children's Oncology Group report ( Fair; 2023) | Frequency of TP53 germline pathogenic variants in anaplastic rhabdomyosarcoma and the genetic factors associated with this type of sarcoma |
| Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children's Oncology Group ( Martin-Giacalone; 2023) | Germline genetic variants and their effect on the outcomes of pediatric rhabdomyosarcoma patients |
| Circulating Tumor DNA Is Prognostic in Intermediate-Risk Rhabdomyosarcoma: A Report from the Children's Oncology Group ( Abbou; 2023) | Significance of analyzing circulating tumor DNA in intermediate-risk rhabdomyosarcoma cases |
| Deep Learning of Rhabdomyosarcoma Pathology Images for Classification and Survival Outcome Prediction ( Zhang; 2022) | Deep learning techniques and analysis of pathology images of rhabdomyosarcoma |
The NCTN biobanks are committed to providing access to biospecimens for researchers for other secondary studies both within and outside the NCTN.
It is essential that scientists from the broader translational cancer research community can search for and access NCTN legacy biospecimens and
associated data. The NCTN Navigator 
provides this service with its comprehensive, user-friendly, searchable database designed to improve access to biospecimens and data collected
from NCTN cancer treatment trials. Following a transparent application and scientific merit review process, the NCTN Core Correlative Science
Committee approves proposals so that researchers from the broader scientific community can receive NCTN biospecimens for critical studies aimed
at advancing cancer treatments. Researchers can also contact the NCTN Groups to inquire about available biospecimens when the NCTN Navigator does
not include a specific trial of interest. Learn more about the NCTN Biobanks and how to
request biospecimens.
NEWS ACROSS DCTD
NCI’s Office of Government and Congressional Relations (OGCR) Works with DCTD
NCI’s OGCR coordinates, monitors, and analyzes Congressional activities related to NCI and facilitates relationships between NCI and Congress. OGCR also works closely with divisions across NCI to coordinate responses to Congress, as well as with other offices at both the institute and agency levels. OGCR has a long history of working with DCTD staff across multiple projects. One recent example was on June 28, when OGCR spearheaded a visit to NCI focused on childhood cancer research with staff to Sens. Tammy Baldwin (D-WI), Shelley Moore Capito (R-WV), and Chris Van Hollen (D-MD), as well as staff to Reps. Kathy Castor (D-FL), and Mike Kelly (R-PA). The group met with NCI extramural program leaders, including DCTD staff Malcolm Smith, MD, PhD and Nita Seibel, MD, and leadership from NCI’s Pediatric Oncology Branch, and participated in two lab tours. The Congressional staff also toured the NIH Clinical Center and The Children’s Inn at NIH.
NCI staff pictured standing from left to right: Dr. Michelle Mollica, Deputy Director of the NCI Office of Cancer Survivorship; Dr. Gregory Reaman, Childhood Cancer Data Initiative Scientific Director; Dr. Carol Thiele, Deputy Chief of the POB; Deputy Director for CCR; and Head, Cell and Molecular Biology Section; Dr. Nita Seibel, Head, Pediatric Solid Tumor Therapeutics, CTEP; Dr. Malcolm Smith, Associate Branch Chief for Pediatric Oncology, CTEP; Dr. Brigitte Widemann, Chief of the POB; Head, Pharmacology and Experimental Therapeutics Section; and Special Advisor on Childhood Cancer to the NCI Director
Visiting staff pictured seated from left to right: Ms. Ijeoma Egekeze (Sen. Chris Van Hollen, MD); Mr. Quinn Ritchie (Rep. Mike Kelly, PA); Ms. Maureen Szemborski, Office of the First Lady; Ms. Dana Richter (Sen. Shelly Moore Capito, WV); Ms. Kiley Mulligan (Sen. Tammy Baldwin, WI); Ms. Capreece Kelsaw (Rep. Kathy Castor, FL)
NCI Program for Natural Product Discovery Prefractionated Library Is Featured on the Cover of ACS Infectious Diseases
The National Institute of Allergy and Infectious Diseases and NCI collaborated on a project to screen more than 300,000 natural products for the potential to fight diseases. Using the NCI Program for Natural Product Discovery (NPNPD), more than 3,000 natural product fractions had possible antimicrobial/fungal activity. Read the publication.
The cover art related to the paper shows the high-throughput process with a structure of a natural product in the center. Learn more about the NPNPD, including how to request samples for your research.
Clinical Proteomic Tumor Analysis Consortium (CPTAC) Releases Proteogenomic Dataset
CPTAC released a comprehensive dataset that standardizes genomic, proteomic, imaging, and clinical data from individual studies of more than 1,000 tumors across 10 cancer types. Cancer researchers can use this publicly available resource to uncover new molecular insights into how cancers develop and progress. The dataset and examples of its potential are described in three papers published in Cell by CPTAC investigators. Read more in NCI’s media advisory “NCI unveils comprehensive proteogenomic dataset to help cancer researchers unravel molecular mysteries.” These papers were also discussed in the September 12, 2023 edition of NIH Research Matters: Advancing molecular insights into cancer.
NCI and ID.me User Access Update
To ensure the security of NCI systems, subjects, staff, and data, Identity Proofing (IP) and Multi-Factor Authentication (MFA) have been incorporated into the user access procedure. These additional security controls will better protect the integrity of all NIH systems using CTEP-IAM and/or NIH credentials. This recent change is required to meet the Presidential and Office of Management and Budget directive on improving the Nation’s cyber security. To meet this requirement, NCI has partnered with ID.me. Read more details on this important update.
NIH Trial Leads to Atezolizumab Approval for Alveolar Soft Part Sarcoma (ASPS) — Data Published in New England Journal of Medicine
On December 9, 2022, the US FDA approved the immunotherapy drug atezolizumab for the treatment of alveolar soft part sarcoma (ASPS). ASPS is a rare disease affecting fewer than 100 people per year in the U.S. Alice Chen, MD, Developmental Therapeutics Clinic (DTC), led the trial that informed the FDA approval. This treatment is not only available now for adults with ASPS, but also for children 2 years and older; this represents the first FDA approval for atezolizumab in the pediatric population. NCI’s press release provides more information on the trial and results.
Since the FDA approval, the complete data from the trial were recently reported in the New England Journal of Medicine.
To accompany the publication, NCI shared a short video on social media “NCI Minute: Immunotherapy for a Rare Cancer.”
In reference to the ASPS trial, Dr. Chen was featured in the Community Stories section of the Childhood Cancer Data Initiative on NCI’s website.
Dr. Alice Chen sits with one of her patients. Credit: National Cancer Institute
Quantum Sensing Podcast
Jeff Buchsbaum, MD, PhD, participated in a 3-part podcast with Ecosystemic Futures. Listen to Part 1 here: Quantum Sensing — A New Era of Wicked Opportunities in Sensing
Background on the podcast from Ecosystemic Futures
Quantum sensing is impacting the way we observe and analyze the world today. It measures activity in the physical world using atomic properties, resulting in the collection of extremely precise information, ultimately helping us understand the inner workings of complex systems at atomic scale. The potential implications are profound. On today’s episode of Ecosystemic Futures, our hosts sit down with Dr. Jeff Buchsbaum, a medical officer at the National Cancer Institute to discuss the applications and implication of Quantum sensing.
New on DCTD Websites
- DCTD has a dedicated page for DCTD-supported research networks, which is located under the Research tab in the top navigation bar of the DCTD homepage.
- DCTD recently launched a detailed webpage for the Cancer Immune Modeling and Analysis Centers (CIMACs) and Cancer Immunologic Data Center (CIDC) Network. You can find information about the network’s history, standardized assays, clinical data standardization and specimens, clinical trials collaborating with CIMAC-CIDC, and publications stemming from the network’s efforts.
- DCTD has updated the methodology for the NCI-60 from a 96-well to a 384-well plate using a high-throughput system. September 30 was the last day to submit compounds to be screened using the traditional screen. Read more about this update.
- A summary and all recordings from the Cancer, Aging, and Immunology webinar series are available on the DCTD Events page. Watch the webinars.
Selected Recent Publications and NCI Cancer Currents Blog Posts
Publications
Coleman CN, Wong R, Petereit DG, et al. NCI’s Cancer Disparities Research Partnership Program: A unique funding model 20 years later. J Natl Cancer Inst. 2023 Sep 14. Online ahead of print. PubMed
Chen AP, Sharon E, O’Sullivan-Coyne G, et al. Atezolizumab for advanced alveolar soft part sarcoma. N Engl J Med. 2023 Sep 7;389(10):911-921. PubMed
Dexheimer TS, Coussens NP, Silvers T, et al. Multicellular complex tumor spheroid response to DNA repair inhibitors in combination with DNA-damaging drugs. Cancer Res Commun. 2023 Aug 25;3(8):1648-1661. PubMed
Flores-Toro JA, Jagu S, Armstrong GT, et al. The Childhood Cancer Data Initiative: Using the power of data to learn from and improve outcomes for every child and young adult with pediatric cancer. J Clin Oncol. 2023 Aug 20;41(24):4045-4053. PubMed
Morris J, Kunkel MW, White SL, et al. Targeted investigational oncology agents (IOA) in the NCI60: A phenotypic systems-based resource. Mol Cancer Ther. 2023 Aug 7. Online ahead of print. PubMed
Dou Y, Katsnelson L, Gritsenko MA, et al. Proteogenomic insights suggest druggable pathways in endometrial carcinoma. Cancer Cell. 2023 Aug 2. Online ahead of print. PubMed
Harris LN, Blanke CD, Erba HP, et al. The new NCI precision medicine trials. Clin Cancer Res. 2023 Aug 2. Online ahead of print. PubMed
Ascierto PA, Agarwala SS, Warner AB, et al. Perspectives in melanoma: Meeting report from the Melanoma Bridge (December 1st-3rd, 2022 — Naples, Italy). J Transl Med. 2023 Jul 28;21(1):508. PubMed
Freidlin B, Korde LA, and Korn EL. Timing and reporting of secondary overall survival end points for phase III trials in advanced/metastatic disease. J Clin Oncol. 2023 Jul 20. Online ahead of print. PubMed.
O’Dwyer PJ, Gray RJ, Flaherty KT, et al. The NCI-MATCH trial: Lessons for precision oncology. Nat Med. 2023 June;29(6):1349-1357. PubMed
Kim MM, Mehta MP, Smart DK, et al. National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: Challenges and recommended priorities. Lancet Oncol. 2023 Aug;24(8):e344-e354. PubMed
McCall SJ, Lubensky IA, Moskaluk CA, et al. The Cooperative Human Tissue Network of the National Cancer Institute: Supporting cancer research for 35 years. Mol Cancer Ther. 2023 Jul 28. Online ahead of print. PubMed
Some people with rectal cancer can skip radiation before surgery; Cancer Currents. July 19, 2023.
FUNDING UPDATES
| Title | Announcement Number | Closing Date | Activity Code |
|---|---|---|---|
| Next generation chemistry centers for fusion oncoproteins (Clinical Trial Not Allowed) | RFA-CA-23-037 | November 16, 2023 | UM1 |
| Mechanisms of fusion-driven oncogenesis in childhood cancers (Clinical Trial Not Allowed) | RFA-CA-23-036 | November 16, 2023 | U01 |
| Innovative research in cancer nanotechnology (IRCN; Clinical Trial Not Allowed) | PAR-23-246 | May 5, 2026 | R01 |
| Assay development and screening for discovery of chemical probes, drugs or immunomodulators (Clinical Trial Not Allowed) | PAR-23-264 | September 8, 2026 | R01 |
| Academic-industrial partnerships (AIP) to translate and validate in vivo imaging systems (Clinical Trial Optional) | PAR-23-259 | January 8, 2027 | R01 |