Last Updated: 02/29/2024

STAFF HIGHLIGHT: Lalitha Shankar, MD, PhD

In this edition of the DCTD newsletter, Lalitha K. Shankar, MD, PhD, Chief, Clinical Trials Branch (CTB), Cancer Imaging Program (CIP), describes her journey in the field of diagnostic imaging and shares exciting advances in imaging 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 master’s degree in biomedical engineering.

How did you choose a career in diagnostic imaging?

Having generations of academics in my family, I had a strong pull to be a clinical researcher and have a career in academics. When I was in medical school in Bangalore University, India, it took some time during clinical rotations to find an interesting specialty. Radiology became the most interesting field to me, particularly molecular and functional imaging. Viewing the pathophysiology of disease and the tumor microenvironment as a whole-body assessment felt thrilling. As a 3rd generation physician, my neurologist father was disappointed that I did not become a neurologist, but that changed after he joined me at a molecular imaging conference. After seeing many presentations of molecular imaging of patients with Parkinson’s disease and dementia, both for diagnosis and treatment response, he got it! Molecular and functional imaging is important for cancer diagnosis and treatment because it can help to find out a variety of tumor characteristics such as the oxygen status and receptor expression in a tumor (e.g., visualizing the estrogen receptor in breast cancer) plus how aggressive it is (proliferative or indolent).

My interest in radiology led me to pursue my master’s and doctorate in radiation sciences at Hahnemann University, Philadelphia. I did my residency in clinical nuclear medicine and completed fellowships in Positron Emission Tomography (PET), radio-immuno-diagnosis, and radio-immunotherapy at the University of Pennsylvania. Prior to joining the NCI in 2003, I was a faculty member in the Department of Radiology at Georgetown University, the Lombardi Cancer Center, and the Division of Nuclear Medicine at Washington Hospital Center in Washington, D.C.

What do you enjoy most about working at NCI?

I enjoy precision medicine, non-invasive imaging, and working across NIH programs and institutes on screening studies, cancer escalation) studies. In DCTD, I evaluate the role of functional and molecular imaging in the diagnosis and treatment of cancer and the performance characteristics of imaging modalities to optimally manage cancer in patients. My work involves establishing and monitoring clinical trials with CTEP to evaluate imaging tracers and techniques, which aim to improve the prevention, diagnosis, and treatment of cancer. CTB provides imaging expertise for trials of cancer diagnostics and therapeutics sponsored by CTEP in the ETCTN, NCTN, and other consortia, as well as the NCI Community Oncology Research Program (NCORP). I’ve worked with the Division of Cancer Control and Population Sciences because I am interested in practice patterns of new diagnostic studies. I have served on several committees, including RECIST, RANO, FDA’s Medical Imaging Drug Advisory Committee, trans-European biomarker initiatives, as well as the Society of Nuclear Medicine and Molecular Imaging (SNMI) as a fellow. I enjoy developing PET-specific INDs with the National Institute of Allergy and Infectious Diseases; collaborating with the National Institute of Biomedical Imaging and Bioengineering and the FDA Center for Device and Radiological Health for medical imaging devices; and partnering with the Centers for Medicare and Medicaid Services to assess payment and registry development for outcome information to fund cancer research. Some of this work helped to facilitate the use of FDG (fludeoxyglucose) and NaF (sodium fluoride) PET to assess the tumor burden in soft tissue and bone. A similar approach was recently used to assess and approve PET agents for diagnosis and monitoring Alzheimer’s disease.

I enjoy conducting workshops with the FDA to educate investigators and companies on how to take products through the clinical phase pipeline and showcase what NCI funds/supports. I also help to manage The Cancer Imaging Archive (TCIA) — maintained now for 12 years. CIP chooses the diagnostic radiology and histopathology imaging collections that are useful to host there. We see investigators harnessing TCIA data to develop informatics tools for screening, diagnosis, and prognosis.

In the imaging field, what challenges remain and what highlights have sparked excitement in the last decade?

A challenge in radiomics is to develop tools beyond screening, and in cancer, we need more predictive markers to help make clinical decisions. I am excited about robotic technology, optical imaging agents and PET imaging for visualizing the prostate specific antigen (PSMA PET) — a highly expressed target in prostate cancer, surgical oncology, and uncovering the molecularly active parts of the tumor. We can then use radionuclide therapy tagged to PSMA that goes to the right area, which improves outcomes, and decreases side effects. Another advancement is that newer fluorescent imaging agents visualize the bladder and ureter clearly and outline the nerves (to avoid damage during surgery), which can be tricky with robotic surgery.

What triumphs has NCI made in imaging, and what do you see on the horizon?

I’m happy to be part of CIP for 20 years. We have funded some of the most exciting research in device development and translational work in chemistry. We funded the first PET CT scanner development plan, which is now a clinical standard. We funded PET MR. For PSMA PET, we have been funding Dr. Marty Pomper (PSMA PET developer at Johns Hopkins University) since day one, and today five distinct PSMA PET agents exist. I find the advances using PSMA for imaging and therapy exciting and encouraging for other cancers. You get to know the phenotype of the tumor and microenvironment and how to personalize medication.

I have worked on studies with the NCI Division of Cancer Prevention on screening and with NCORP to help determine how to intensify or de-intensify therapy. Some cancers can be more indolent, and we can decrease therapy to reduce the side effects from radiation — how amazing! Similar improvements in MRI with functional imaging help to show tumor vascularization and aggressiveness.

For the future, NCI, the American Society of Clinical Oncology, FDA, and others are striving to improve the ease for patients to be part of clinical trials. Emphasis is on collaborating with professional societies, such as SNMI, to educate imaging physicians about advanced imaging for trials and its value for clinical care. For NCI studies, our patients wouldn’t have to travel far to cancer centers but could go to local diagnostic clinics if advanced imaging were accessible at local hospitals. The American College of Radiology has established levels of excellence for certification for breast MR and for prostate MR so sites can be qualified. I find it heartwarming to see improvement in community oncology practices where work has extended to the NCI Center for Global Health.

What advice would you give to someone aspiring to follow in your footsteps?

A degree in medicine, training in molecular imaging, and an interest in research are important. You should also have a sense of research fundamentals and be open and imaginative to forge partnerships to improve the patient experience.

SPOTLIGHT: Phase 2 Trial in the Developmental Therapeutics Clinic Informs FDA Approval of Nirogacestat

NCI’s Developmental Therapeutics Clinic (DTC) conducted a pivotal phase 2 trial that examined nirogacestat (PF-03084014; a gamma-secretase inhibitor) in patients with rare desmoid tumors. Desmoid tumors arise from connective tissue cells or fibroblasts and are slow growing, locally invasive, and difficult-to-treat. In the DTC trial, five of 17 (29%) patients experienced a confirmed partial response (~50% reduction of the tumor) as their best response, and another five had prolonged stable disease when treated with PF-03084014 (Kummar, 2017 ). The clinically beneficial phase 2 results propelled the 2019 launch of a phase 3 trial conducted outside of the DTC. In the phase 3 trial, patients experienced improved progression-free survival, and the objective response rate was 41% with nirogacestat versus 8% with placebo (p<0.001) using the RECIST v1.1 criteria. In November 2023, nirogacestat became the first FDA approved treatment for adult patients with progressing desmoid tumors who require systemic treatment. the last day to ll be tested in the modernized NCI-60 HTS384 screen.

SPOTLIGHT — DCTD’s Public Webinar Series

NCI Imaging Community Webinar Series

The NCI Cancer Imaging Program (CIP) hosts a monthly webinar series that serves as a community gathering point for scientists and clinicians interested in advances in cancer imaging. The webinars are open to the public and are typically held on the first Monday of each month from 1:00 to 2:00 pm ET. The webinar recordings are posted after the event.

The goals of the series are to provide a forum for engagement, raise awareness, and accelerate a path for innovative thinking that has the potential to transform research for the benefit of patients with cancer and their caregivers. The webinars seek to showcase current research directions in the field and stimulate interdisciplinary dialog on selected cancer imaging topics.

Webinar topics of interest will include, but are not limited to:

• New imaging technologies for cancer diagnosis
• Advances in nanotechnology to improve cancer diagnosis and treatment
• Artificial Intelligence to improve research and clinical imaging workflow
• Deep learning integration and analysis of medical imaging data for patient outcome assessment
• Intraoperative procedures to improve cancer surgical outcome
• Improvements in image guided therapies
• Molecular imaging to understand current concepts in cancer tumor biology
• Molecular imaging of cellular therapy response
• Imaging data integration with genetics/proteomics/other biological data to understand cancer biology

For more information on the webinar series, please contact Dr. J. Manuel Perez (jmanuel.perez@nih.gov).

Biobanking for Precision Medicine Seminar Series

NCI’s Biorepositories and Biospecimen Research Branch (BBRB), CDP, hosts the Biobanking for Precision Medicine seminar series, which is open to the public.

In the era of precision medicine, high quality biospecimens are central to understanding complex diseases, biomarker discovery, and unraveling the mechanisms of resistance to therapies. The seminar series addresses current topics in biobanking science, policy, and operations, with the goal of improving awareness of best practices for the collection of biospecimens and associated data as well as expanding research participation through biobanking.

The fall 2023 series encompassed four seminars focused on the theme of data sharing in biobanking studies and research that uses biospecimens. The 2024 series will focus on Biospecimen Science, and the webinar recordings for many previous sessions are available to view. For more information on the webinar series, please contact Dr. Veena Gopalakrishnan (veena.gopalakrishnan@nih.gov) in BBRB.

DCTD Diversity, Equity, Inclusion, and Accessibility (DEIA) Update

By Leah Hubbard, PhD, DCTD Chief Diversity Officer

In 2023, we focused our goals in three major areas to improve DEIA in our division:

• Implementing career development tools for DCTD staff.
• Implementing new procedures to promote transparency and equity in DCTD staff promotion and awards.
• Incorporating our DEIA mission and commitments on the DCTD website.

We were able to accomplish these goals and more, including:

• Launching the DCTD Individual Development Plan (IDP) for DCTD employees to explore relevant training opportunities and map out professional goals, either independently or with support from their supervisor.
• Collaborating with the Administrative Resource Center (ARC) to implement new benchmark procedures for GS-15 Health Scientist Administrator (601) positions and administrative staff award nominations.
• Collaborating with DCTD OD Communications to launch the DCTD DEIA webpage and to recognize staff contributions and participation in commemorative month celebrations in our newsletter and on social media.
• Convening regular DEIA meetings with DCTD leadership and the ARC to assess the workplace climate, evaluate recruitment/hiring procedures, identify areas for improvement, and implement new initiatives.
• Collaborating with the NCI Equity and Inclusion Program Working Group 3 to develop an NCI hiring best practices toolkit/training as well as formal recommendations to improve operational efficiencies in the NCI hiring process.

In 2024, we will continue to build upon these efforts and focus on implementing best practices to promote DEIA in our division’s recruitment and hiring process. If you have any questions, feedback, or would like more information on how to support DCTD DEIA, please contact Dr. Leah Hubbard (leah.hubbard@nih.gov), DCTD Chief Diversity Officer. Please visit DCTD’s DEIA webpage for additional resources.

Staff Commemorative Month Celebrations

We are pleased to honor Hispanic Heritage Month (HHM), National Disability Employment Awareness Month (NDEAM), and Native American Heritage Month in this newsletter edition.

In honor of HHM, John Giraldes, Program Manager for the NCI Experimental Therapeutics (NExT) Program, shares how his heritage shaped his value system and eventual career path to the NCI.

My father’s side of the family is an even mix of Hispanic and Latino heritage. From a young age, my grandfather (third-generation Spanish) and grandmother (second-generation Mexican) experienced discrimination because of their background. In response, they reacted with shame and dismissal of their heritage, particularly so with my grandfather. He allowed the shame to bleed into his children and grandchildren, ultimately resulting inSpanish not being passed down and the loss of communication with our extended family — folks I would never know. My last name (Giraldes) was one area that could not be extricated, although the influence of such shame still manifested as a need to Americanize the pronunciation to “JIR-AL-DES” instead of “HE-rrrAL-DEZ,” the correct Spanish pronunciation. I learned my last name originated from a 12th century minaret, and later, a belltower in Seville Spain, called the Giralda tower. Named after the sculpture (known as the Giraldillo) atop the belltower, the Giralda tower was regarded as a symbol of strength, faith, and hope. This landmark would serve as an icon from which to base surnames. It was somewhat ironic that a name’s meaning could impart such a diametric feeling in me.

As I began learning more about science and medicine in college, I came across a disease called Non-Alcoholic Fatty Liver Disease (NAFLD), and its more severe case, Nonalcoholic steatohepatitis (NASH). I learned that NAFLD and NASH tended to disproportionately affect the Hispanic/Latino populations, the cause of which was a variant in the Palatin-like phospholipase domain-containing protein 3 (PNPLA3) gene prevalent in people of Hispanic origin. Liver disease was no stranger to my family, as I had lost my father at 12 years old due to the disease. As time progressed, liver disease was eventually displaced by yet another disease with the loss of my mother and three of my four grandparents in my early 20s to cancer.This left little question about what I would pursue as a career. Now, as a cancer drug research chemist, I found passion in addressing the shortage of quality cancer treatments by helping to develop new drug treatment options for cancer patients. The call was there. I just had to answer it.

When asked what working at the NCI means to me, I say “EVERYTHING.” It means taking my experiences from academic and private sectors and pairing this with knowledge from other talented NCI researchers to treat cancer and improve quality of life. It means using the soft skills and experiences that have shaped my life to shepherd and foster research projects with an eye towards the bigger message. And most of all, it means addressing my mission to alleviate suffering from cancer and disease, so no one endures such hardships. These mantras drove me while in the private sector and continue to drive me at the NCI and within the DCTD. In the DCTD, I see a collection of individuals that can impact and shape the way we treat disease and directly improve quality of life through science. How could this not mean everything?

Because of my Hispanic heritage, I am where I am today. I was able to redefine what being of Hispanic heritage means to me and not adopt the negative association my grandfather experienced. I was able to redirect those experiences into a positive message embodying strength, faith, and hope — the meaning from which my family name was drawn — and build a legacy that will shape my children and others around me.

Hispanic Heritage Month

With a national theme of “Latinos: Driving Prosperity, Power, and Progress in America,” NIH recognized HHM from September 15th – October 15th to celebrate the culture and contributions of Latino and Hispanic Americans. Beginning in 1968 as Hispanic Heritage Week under President Johnson, the commemoration was expanded in 1988 by President Reagan to a full month celebration. September 15th is an important date, as it commemorates independence days for Costa Rica, El Salvador, Guatemala, Honduras, and Nicaragua. Further underscoring the mid-month commencement of HHM, September 16th marks the beginning of the Mexican War of Independence, and September 18th commemorates the independence of Chile from Spain.

National Disability Employment Awareness Month

October marks NDEAM, which recognizes the contributions people with disabilities bring to the workforce. The 2023 theme of “Advancing Access and Equity” was highlighted across NIH in a series of events, including the NCI Center for Cancer Research’s (CCR) “Celebrating National Disability Employment Awareness Seminar Series.” The series featured several talks on Navigating Biomedical Research and Creating an Inclusive Environment and a talk on Best Practices in Mentoring Deaf Scientists presented by Dr. Derek Braun, Professor in the School of Science, Technology, Accessibility, Mathematics, & Public Health at Gallaudet University. In addition, the NIH Office of Equity, Diversity, and Inclusion featured a number of NDEAM articles, including a story about two NCI CCR scientists who are deaf.

Native American Heritage Month

With the earliest commemorations beginning in 1915 as First Americans Day, November was officially designated as National American Indian Heritage Month in 1990 to highlight the culture, perseverance, and contributions of the nation’s original inhabitants and their descendants, including Alaska Native, Native Hawaiian, and affiliated Island communities. In celebration of Native American Heritage Month (NAHM), NIH established the theme, “Indigenous Resilience and Cultural Revitalization” and supported a number of events across DHHS. This included an NCI Division of Cancer Control and Population Sciences talk entitled, Beyond Survivance: Thrivance Among American Indian and Alaska Native Cancer Survivors, presented by Dr. Karina L. Walters, Director of the NIH Tribal Health Research Office. Dr. Walters highlighted cancer burden and challenges in screening, diagnosis, and treatment in the American Indian and Alaska Native population. NIH’s 2023 NAHM celebration also marked the establishment of the Indigenous at NIH Employee Resource Group (ERG) dedicated to improving cultural competency, enhancing recruitment efforts, and identifying funding opportunities for Tribal Colleges and Universities. To join the Indigenous at NIH ERG, contact edi.native@mail.nih.gov.

NEWS ACROSS DCTD

From NCI’s Cancer Currents Blog — What Comes afterNCI-MATCH? NCI’s New Precision Medicine Cancer Trials

More than 8 years ago, NCI launched NCI-MATCH, a first-of-its-kind precision medicine cancer clinical trial. NCI-MATCH tested different targeted therapies in people with cancer whose tumors had specific genetic changes. This year, three second-generation precision medicine trials — ComboMATCH, MyeloMATCH, and iMATCH — are getting underway to build on the knowledge generated by NCI-MATCH and other NCI precision oncology initiatives. In this Cancer Currents blog, DCTD Director James H. Doroshow, MD reflects on the accomplishments of NCI-MATCH and offers an overview of these three successor trials.

The Translational Research Program (TRP) Announces Fiscal Year 2023 SPORE Grantees

TRP recently announced its successfully competed FY2023 SPORE grantees. The SPORE program uses the P50 and U54 grant funding mechanisms to promote collaborative, interdisciplinary, translational cancer multi-project research. SPOREs are primarily focused on organ site disease, but also on themes that cut across organ sites. Read about the grantees and their projects.

Dr. Lisa McShane Participates in Friends of Cancer Research (Friends) Panel

Dr. Lisa McShane, Associate Director, Research Program participated in a panel at the Friends’ February 1, 2024 workshop: The Future of Diagnostic Tests: New Data & Modern Policy. The panel was in Session 1: Aligning on Approaches to Measuring Homologous Recombination Deficiency (HRD): Findings from the HRD Harmonization Project. Learn more on the Homologous Recombination Harmonization Project , in which Dr. McShane has been involved. Watch the meeting recording .

The NCI Formulary Expands to Offer Six Additional Agents

The NCI Formulary is a public-private partnership between NCI and pharmaceutical and biotechnology companies that offers investigators at NCI-audited clinical research centers in the United States who are main member sites of the NCI National Clinical Trials Network (NCTN) and the Experimental Therapeutics Clinical Trials Network (ET CTN) rapid access to agents for clinical research or to any U.S. investigators for preclinical research.

The following six agents from Genentech were added to the NCI Formulary in fall 2023:
Giredestrant
Glofitamab
Inavolisib
Pertuzumab/trastuzumab/hyaluronidase-zzxf
Tiragolumab
Trastuzumab and hyaluronidase-oysk

The availability of agents through the NCI Formulary expedites the start of clinical trials by alleviating the lengthy agreement negotiation process — sometimes up to 18 months — required for investigators to access such agents on their own.

Following company approval, investigators can obtain NCI Formulary agents and test them in new preclinical or clinical studies, including combination studies of Formulary agents from different companies. For more information, contact NCIFormulary@mail.nih.gov.

Podcasts, Selected Recent Publications, and NCI Cancer Currents Blog Posts

Listen to the Cancer Healthcast featuring Dr. Lyndsay Harris, Associate Director, CDP, DCTD, and Dr. Peter O’Dwyer, Group Chair, ECOG-ACRIN: The Profound Impacts of Precision Medicine, Genomic Sequencing on Cancer Care; September 25, 2023

Liu Q, Zhang J, Guo C, et al. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell. 2024 Jan 4;187(1):184-203.e28. PubMed

Cecchini M, Cleary JM, Shyr Y, et al. NCI10066: A phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma. Br J Cancer. 2023 Dec 22. Online ahead of print. PubMed

Mittra A, O’Sullivan Coyne GH, Zlott J, et al. Pharmacodynamic effects of the PARP inhibitor talazoparib (MDV3800, BMN 673) in patients with BRCA-mutated advanced solid tumors. Cancer Chemother Pharmacol. 2023 Nov 27. Online ahead of print. 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 Oct 2;22(10):1144-1153. PubMed

Bewersdorf JP, Shallis RM, Sharon, E, et al. A multi-phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Ann Hematol. 2024 Jan;103(1):105-116. PubMed

Zhao, Y, Yuan Y, Korn EL, and Freidlin B. Backfilling patients in phase I dose escalation trials using Bayesian optimal interval design (BOIN). Clin Cancer Res. 2023 Dec 1. Online ahead of print. PubMed

Toner K, Allen CE, Jain S, et al. Overcoming barriers to drug development and enrollment in clinical trials for adolescents and young adults with lymphoma. EJHaem. 2023 Sep 7;4(4):921-926. PubMed

Virtual mind-body fitness classes show unexpected benefit in people with cancer; December 15, 2023

What comes after NCI-MATCH? NCI’s new precision medicine cancer trials; December 6, 2023

Trial results confirm effectiveness of atezolizumab against a rare sarcoma; October 20, 2023

 

FUNDING UPDATES

Title	Announcement Number	Closing Date	Activity Code
Cancer Adoptive Cellular Therapy Network (Can-ACT for Pediatric Cancers (Clinical Trial Required)	RFA-CA-24-021	March 7, 2024	UG3/UG4
Notice of Special Interest (NOSI): Administrative Supplements to Support the Development of Digital Twins in Radiation Oncology (DTRO) Recording from January pre-application webinar	NOT-CA-24-015	March 22, 2024	NOSI
NCI’s Investigator-Initiated Early Phase Clinical Trials for Cancer Treatment and Diagnosis (Clinical Trial Required)	PAR-24-085	January 8, 2027	R01
Notice of Special Interest (NOSI): Quantum Sensing Technologies in Biomedical Applications	NOT-EB-23-022	January 27, 2027	NOSI
Notice of Special Interest (NOSI): Research Projects to Develop Oncoaging Models for Cancer Research	NOT-CA-23-092	July 31, 2027	NOSI
Notice of Intent to Publish a Notice of Funding Opportunity for NCI’s Specialized Programs of Research Excellence (SPOREs) in Cancer Health Disparities and Minority Health (Clinical Trial Optional)	NOT-CA-24-008	First estimated Application Due Date: September 25, 2024