Division Of Cancer Prevention Research Articles

NCI Resources for Cancer Immunoprevention Research.

Cancer prevention and early detection, the first two of the eight primary goals of the National Cancer Plan released in April 2023, are at the forefront of the nation's strategic efforts to reduce cancer incidence and mortality. The Division of Cancer Prevention (DCP) of the NCI is the federal government's principal component devoted to promoting and supporting innovative cancer prevention research. Recent advances in tumor immunology, cancer immunotherapy, and vaccinology strongly suggest that the host immune system can be effectively harnessed to elicit protective immunity against the development of cancer, that is, cancer immunoprevention. Cancer immunoprevention may be most effective if the intervention is given before or early in the carcinogenic process while the immune system remains relatively uncompromised. DCP has increased the emphasis on immunoprevention research in recent years and continues to expand program resources and interagency collaborations designed to facilitate research in the immunoprevention field. These resources support a wide array of basic, translational, and clinical research activities, including discovery, development, and validation of biomarkers for cancer risk assessment and early detection (Early Detection Research Network), elucidation of biological and pathophysiological mechanistic determinants of precancer growth and its control (Translational and Basic Science Research in Early Lesions), spatiotemporal multiomics characterization of precancerous lesions (Human Tumor Atlas Network/Pre-Cancer Atlas), discovery of immunoprevention pathways and immune targets (Cancer Immunoprevention Network), and preclinical and clinical development of novel agents for immunoprevention and interception (Cancer Prevention-Interception Targeted Agent Discovery Program, PREVENT Cancer Preclinical Drug Development Program, and Cancer Prevention Clinical Trials Network).

Natural Products for Cancer Prevention and Interception: Preclinical and Clinical Studies and Funding Opportunities.

Multiple agents derived from natural products (NPs) have been evaluated for cancer prevention and interception, either alone or in combination. The National Cancer Institute (NCI) is very interested in advancing research to identify additional agents that, alone or in combination, may prove useful in cancer prevention. Below, we provide an overview of NP studies in cancer prevention and interception, both individual agents and combination interventions. Given that findings from many preclinical studies evaluating individual agents have generally not been confirmed in human studies, our focus with individual NPs in this review is on studies involving humans, especially clinical trials. Fewer combination intervention studies have been conducted, so we have broadened our review to include preclinical studies. We conclude with how the Division of Cancer Prevention (DCP) within the NCI is providing funding to encourage the research community to propose natural product studies in cancer prevention and interception to advance the field.

Consensus-based framework for evaluating data modernization initiatives: the case of cancer registration and electronic reporting.

As part of its data modernization initiative (DMI), the Centers for Disease Control and Prevention, Division of Cancer Prevention and Control is testing and implementing innovative solutions to improve cancer surveillance data quality and timeliness. We describe a consensus-based effort to create a framework to guide the evaluation of cancer surveillance modernization efforts by addressing specific context, processes, and costs related to cancer registration. We drew on prior theories, consulted with experts, and sought feedback from cancer registry staff. We developed the cancer surveillance systems, context, outcomes, and process evaluation (CS-SCOPE) framework to explain the ways in which cancer registry data quality, timeliness, and efficiency are impacted by external and internal contextual factors and interrelated process and content factors. The framework includes implementation measures to understand acceptability of process changes along with outcome measures to assess DMI initiation and ongoing sustainability. The framework's components and structures can be tailored for use in other DMI evaluations.

Lynch syndrome: toward an increasingly complex picture. The case of PMS2.

Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, Milan, Italy Received 28 February 2023 Accepted 28 February 2023. Correspondence to Mariarosaria Calvello, Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, Milan, Italy, E-mail: [email protected]

Lessons from the Failure to Complete a Trial of Denosumab in Women With a Pathogenic BRCA1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy.

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes.

PLCOjs, a FAIR GWAS web SDK for the NCI Prostate, Lung, Colorectal and Ovarian Cancer Genetic Atlas project.

The Division of Cancer Epidemiology and Genetics (DCEG) and the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) have recently generated genome-wide association study (GWAS) data for multiple traits in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Genomic Atlas project. The GWAS included 110000 participants. The dissemination of the genetic association data through a data portal called GWAS Explorer, in a manner that addresses the modern expectations of FAIR reusability by data scientists and engineers, is the main motivation for the development of the open-source JavaScript software development kit (SDK) reported here. The PLCO GWAS Explorer resource relies on a public stateless HTTP application programming interface (API) deployed as the sole backend service for both the landing page's web application and third-party analytical workflows. The core PLCOjs SDK is mapped to each of the API methods, and also to each of the reference graphic visualizations in the GWAS Explorer. A few additional visualization methods extend it. As is the norm with web SDKs, no download or installation is needed and modularization supports targeted code injection for web applications, reactive notebooks (Observable) and node-based web services. code at https://github.com/episphere/plco; project page at https://episphere.github.io/plco.

Lessons Learned from the Impact of COVID-19 on NCI-sponsored Cancer Prevention Clinical Trials: Moving Toward Participant-centric Study Designs.

The COVID-19 pandemic overloaded health care systems around the globe and brought travel restrictions and other mandates. These effects critically impacted cancer care and conduct of clinical trials, and required medical and research communities to incorporate changes and novel flexible workflows within clinical trials and regulations to improve efficiency. We report the impact of the pandemic on cancer prevention clinical trials managed by the Division of Cancer Prevention within the NCI, focusing on participant-centric, study staff-centric and regulatory elements. Learning lessons from this challenging period, the cancer prevention community has the opportunity to incorporate many of these necessitated novel approaches to future design of clinical trials, to streamline and improve clinical trial efficiency and impact.

Report from an NCI Roundtable: Cancer Prevention in Primary Care.

The Division of Cancer Prevention in the NCI sponsored a Roundtable with primary care providers (PCP) to determine barriers for integrating cancer prevention within primary care and discuss potential opportunities to overcome these barriers. The goals were to: (i) assess the cancer risk assessment tools available to PCPs; (ii) gather information on use of cancer prevention resources; and (iii) understand the needs of PCPs to facilitate the implementation of cancer prevention interventions beyond routine screening and interventions. The Roundtable discussion focused on challenges and potential research opportunities related to: (i) cancer risk assessment and management of high-risk individuals; (ii) cancer prevention interventions for risk reduction; (iii) electronic health records/electronic medical records; and (iv) patient engagement and information dissemination. Time constraints and inconsistent/evolving clinical guidelines are major barriers to effective implementation of cancer prevention within primary care. Social determinants of health are important factors that influence patients' adoption of recommended preventive interventions. Research is needed to determine the best means for implementation of cancer prevention across various communities and clinical settings. Additional studies are needed to develop tools that can help providers collect clinical data that can enable them to assess patients' cancer risk and implement appropriate preventive interventions.

Computable Guidelines and Clinical Decision Support for Cervical Cancer Screening and Management to Improve Outcomes and Health Equity.

Cervical cancer is highly preventable when precancerous lesions are detected early and appropriately managed. However, the complexity of and frequent updates to existing evidence-based clinical guidelines make it challenging for clinicians to stay abreast of the latest recommendations. In addition, limited availability and accessibility to information technology (IT) decision supports make it difficult for groups who are medically underserved to receive screening or receive the appropriate follow-up care. The Centers for Disease Control and Prevention (CDC), Division of Cancer Prevention and Control (DCPC), is leading a multiyear initiative to develop computer-interpretable ("computable") version of already existing evidence-based guidelines to support clinician awareness and adoption of the most up-to-date cervical cancer screening and management guidelines. DCPC is collaborating with the MITRE Corporation, leading scientists from the National Cancer Institute, and other CDC subject matter experts to translate existing narrative guidelines into computable format and develop clinical decision support tools for integration into health IT systems such as electronic health records with the ultimate goal of improving patient outcomes and decreasing disparities in cervical cancer outcomes among populations that are medically underserved. This initiative meets the challenges and opportunities highlighted by the President's Cancer Panel and the President's Cancer Moonshot 2.0 to nearly eliminate cervical cancer.

Hospital-based ovarian cancer patient traceback program results in minimal genetic testing uptake

ObjectiveTo determine the feasibility of hospital-based genetic counseling and testing (GC/T) Traceback for Ovarian Cancer (OC) patients, as proposed by the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute. MethodsLiving patients with OC were sent a letter explaining the availability of guideline-supported GC/T for at least BRCA1/2 and surrogates of deceased patients were called on the telephone. Outcomes of contact attempts were systematically recorded and statistically described. Results598 Traceback-eligible OC patients diagnosed from 2006 to 2016 were identified (163 presumed-living and 435 deceased). Two living patients called our office and scheduled an appointment for GC/T after receiving a letter. For surrogates of prior patients, successful contact occurred in 25% of call attempts. Fourteen individuals (2 living patients and 12 surrogates) underwent genetic counseling. Of those 14, 10 individuals consented to genetic testing and 5 followed through with sample collection. None of these individuals had pathogenic variants (PVs). When surrogate call notes were reviewed, 58% reflected positive responses to contact, however 42% were noted to have negative or indifferent responses, which were most common among spouses. Total time spent for hospital-based Traceback was 109 h. ConclusionsOverall, hospital-based Traceback via letter and telephone contact of surrogates is time-intensive and results in minimal uptake of GC/T. To practically execute this type of outreach program, health systems should consider collection of alternative contact information to allow for electronic communication of patient surrogates. Our study also underscores the importance of timely GC/T while patients are in active cancer care.

Translational Advances in Cancer Prevention Agent Development (TACPAD) Virtual Workshop on Immunomodulatory Agents: Report.

The National Cancer Institute (NCI) Division of Cancer Prevention (DCP) convened the “Translational Advances in Cancer Prevention Agent Development (TACPAD) Workshop on Immunomodulatory Agents” as a virtual 2-day workshop on September 13 to 14, 2021. The main goals of this workshop were to foster the exchange of ideas and potentially new collaborative interactions among leading cancer immunoprevention researchers from basic and clinical research and highlight new and emerging trends in immunoprevention. The workshop included an overview of the mechanistic classes of immunomodulatory agents and three sessions covering the gamut from preclinical to clinical studies. The workshop convened individuals working in immunology and cancer prevention to discuss trends in discovery and development of immunomodulatory agents individually and in combination with other chemopreventive agents or vaccines.

Hospital-based traceback program for prior ovarian cancer patients results in minimal uptake of genetic counseling and testing

<h3>Objectives:</h3> Objective: To determine the feasibility of a hospital-based approach to implementation of a genetic testing traceback program for ovarian cancer patients <h3>Methods:</h3> The Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute (NCI) recognized the opportunity lost by the lack of genetic counseling and/or testing (GC/T) for <i>BRCA1</i> and <i>BRCA2</i> in previously diagnosed women with ovarian cancer (OC). During a 2016 workshop, they coined the term ‘traceback' to describe the concept of offering GC/T to these patients and families that should have been offered services previously. We identified traceback-eligible patients and patient-designated surrogates (emergency contacts, medical power-of-attorney designees, family members) using tumor registry and electronic medical record data. Eligible patients had histology-confirmed epithelial malignancies of ovarian, fallopian tube, or peritoneal origin. All living patients were sent a letter explaining the availability of GC/T and surrogates of deceased patients were called on the telephone. Outcomes of contact attempts were systematically recorded and statistically described. <h3>Results:</h3> We identified 176 presumed-living and 441 deceased trace-back-eligible OC patients diagnosed between 2006-2016. For living patients, 6% (n=11) of letters were returned without forwarding address and 1% (n=2) contacted our office upon receipt of the letter and scheduled genetic counseling visits. Telephone numbers but no other contact information details were available for at least one surrogate for 91% (n=401) of deceased patients. The most commonly listed primary surrogates were spouses (41%) followed by daughters (21%). Approximately 20% (n=.77) of contact attempts to primary surrogates have resulted in a phone conversation about the availability of GC/T. More than half (64%) have required more than one call. Of the primary surrogates successfully contacted, 40% have previously heard of GC/T for OC before, 28% have discussed GC/T with their healthcare providers, 9% had already had GC/T and 13% were interested in GC/T at this time. Phone numbers were invalid for 20% of primary contacts. Overall, hospital-based traceback resulted in GC/T for 2% of those patients and surrogates contacted. <h3>Conclusions:</h3> While feasible, telephone-based contact of patient-designated surrogates is time-intensive and results in minimal uptake of GC/T. To practically execute this type of outreach program, health systems should consider collection of alternative contact information details like email addresses for surrogates and should consider the development of family registries for future contact.

Abstract 110: Planned versus observed effect sizes in early phase chemoprevention trials

Abstract Early phase chemoprevention trials are designed to demonstrate safety, tolerability, feasibility, and signals of efficacy. Yet it is often observed that most trials fail to detect intervention effects. The purpose of this review was to analyze intervention effects in such trials by comparing planned vs observed effect sizes. Single or multi-arm efficacy and biomarker chemoprevention trials conducted under the Phase 0-II Cancer Prevention Clinical Trial Program of the Division of Cancer Prevention, National Cancer Institute between 2003 and 2019 were evaluated. Protocols were reviewed to gather information regarding study design, primary endpoint(s), analysis plan, analysis population(s), and sample size justifications with planned effect sizes. Reports and manuscripts were reviewed to obtain study results information. Intervention effects for differences were quantified by calculating standardized Cohen's d effect sizes. In studies where only p-values were reported without effect sizes, observed effect sizes were estimated using p-values and sample size information. Planned effect sizes were compared to observed effect sizes and post-hoc power calculations were conducted. Of a total of 59 trials reviewed, twenty-four trials were efficacy or biomarker studies with complete information on planned and observed effect sizes. Organ sites of focus included 5 (21%) breast, 6 (25%) prostate, 4 (17%) lung, and 9 (38%) gastrointestinal and other sites. The majority of the trials (n=18) were multi-arm randomized studies of which 15 trials were blinded. The median planned effect size for detecting an intervention effect was 0.75 (range 0.2-1.14), while the median planned sample size per arm was n=30 (range 11-101). The planned effect sizes were larger than the observed effects sizes in the majority of the studies (88%). The observed effect sizes in most studies were small with a median of 0.34 (range 0-0.66). The median difference between planned vs observed effect size was -0.37. A low level of concordance between planned vs observed effect size was observed with an intra-class correlation coefficient 0.18 (95% CI: -0.1-0.50). The median post-hoc power for detecting the observed effect sizes was only 0.29 (range 0.03-0.93). There were no significant differences detected between planned vs observed effect sizes when stratified by accrual goals, analysis populations, or study design (multi-arm randomized vs single arm). The results indicate that the majority of early phase chemoprevention trials have much smaller observed effect sizes than planned. Sample size calculations for such trials need to balance the known attributes of the study endpoints, e.g. the potential detectable effect sizes in populations that can be realistically and cost-effectively accrued, with the need to detect only effect sizes large enough to justify subsequent phase III trials. Utilization of interim analyses for futility may be considered. Citation Format: Jens C. Eickhoff, Jen Birstler, Guanhua Chen, Zhumin Zhang, Vikrant Sahasrabuddhe, Eva Szabo, KyungMann Kim. Planned versus observed effect sizes in early phase chemoprevention trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 110.

Report of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development–sponsored workshop: gynecology and women’s health–benign conditions and cancer

The Division of Cancer Prevention and the Division of Cancer Biology at the National Cancer Institute and the Gynecologic Health and Disease Branch in the National Institute of Child Health and Human Development organized a workshop in April 2019 to explore current insights into the progression of gynecologic cancers from benign conditions. Working groups were formed based on 3 gynecologic disease types: (1) Endometriosis or Endometrial Cancer and Endometrial-Associated Ovarian Cancer, (2) Uterine Fibroids (Leiomyoma) or Leiomyosarcoma, and (3) Adenomyosis or Adenocarcinoma. In this report, we highlight the key questions and current challenges that emerged from the working group discussions and present potential research opportunities that may advance our understanding of the progression of gynecologic benign conditions to cancer.

Abstract C62: The Alliance of Ppancreatic Cancer Consortia for Biomarkers for Early Detection

Abstract Pancreatic cancer is the fourth leading cause of cancer death in the United States and the 5-year relative survival for patients diagnosed with pancreatic cancer is less than 10%. Early intervention is the key to a better survival outcome. Currently, there are no biomarkers that can reliably detect pancreatic cancer at an early stage or identify precursors that are destined to progress to malignancy. The Alliance of Pancreatic Cancer Consortia for Biomarkers for Early Detection was formed under the auspices of a workshop organized by the National Cancer Institute in partnership with the Kenner Family Research Fund and the Pancreatic Cancer Action Network (December 5, 2016). The second, biannual workshop of the Alliance was convened December 12, 2018. The organizers of this workshop included Drs. Ralph Hruban, Kenneth Kinzler, Stephen Pandol, Brian Wolpin, Walter Park, Samir Hanash, and Anirban Maitra. Investigators from four NCI-supported consortia on pancreatic cancer detection, including the Pancreatic Cancer Detection Consortium (PCDC), the Early Detection Research Network (EDRN), the Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC), and the Consortium for Molecular and Cellular Characterization of Screen-Detected Lesions (MCL), were invited to participate in the workshop. Other invited participants included members of the Kenner Family Research Fund, the Pancreatic Cancer Action Network, investigators from industry, and biostatisticians from NCI‘s Division of Cancer Prevention, Biometry Research Group, and from the EDRN. The keynote speakers included Dr. Ralph Hruban from Johns Hopkins University who spoke about the challenges in pancreatic cancer research, and Dr. James Abbruzzese from Duke Cancer Institute who provided an updated report from NCI’s Scientific Framework for Pancreatic Ductal Adenocarcinoma (PDAC), which met shortly before the workshop. The focus of the workshop included discussion of the molecular characterization of PDAC and its precursors and methodologies for early detection of pancreatic cancer, new imaging applications and artificial intelligence for mining big data, development and utilization of new methods for biomarker validation, and biospecimen science and resources. The members of the workshop agreed that the Alliance should immediately begin working on the development of a repository for images collected prior to the diagnosis of pancreatic cancer. These images could be shared with the Alliance members and would be useful for development of imaging biomarkers. Working with the NCI, the Alliance has begun establishing the common data elements (CDE) needed to develop a repository of pancreatic cancer images. The Alliance of Pancreatic Cancer Consortia provides a valuable forum for investigators and collaborators to discuss and address early detection of pancreatic cancer. Citation Format: Matthew R. Young, Natalie Abrams, Sharmistha Ghosh-Janjigian, Guillermo Marquez, Jo Ann Rinaudo, Sudhir Srivastava. The Alliance of Ppancreatic Cancer Consortia for Biomarkers for Early Detection [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C62.

Abstract C21: Investing in public-private partnerships to address breast cancer disparities among African-American women (low-income) within a non-Medicaid ACA expansion state and Appalachian region

Abstract The purpose of this presentation is to demonstrate how a national network can address breast cancer disparities among low socioeconomic status (SES) female populations by investing in local infrastructure, and innovative public-private partnerships in a state (non-Medicaid expansion) located within the Appalachian region. Public Health Significance: Medically underserved populations are more likely to be diagnosed with a late-stage disease (e.g., cancer). Breast cancer incidence and mortality rates continue to vary by race, ethnicity, age, and geography along with socioeconomic status factors (e.g., level of education, household income, health insurance coverage, etc.). Breast cancer mortality rates among women continue to remain higher in specific regions (including the Appalachian and Southern regions). Among women, African-American (Black) women possess the highest breast-cancer mortality rates. Moreover, studies have revealed that Memphis, Tennessee is one of the 25 largest cities in the United States characterized by racial disparities associated with high breast-cancer mortality rates among African-American (Black/non-Hispanic) women. In an effort to address breast cancer disparities through partnerships, capacity-building, and ultimately stronger community-clinical linkages, SelfMade Health Network (SMHN)'s multidimensional approach involves an investment in some regions disproportionately characterized by high rates of breast cancer incidence or mortality. SMHN is the most recent member of the Centers for Disease Control and Prevention (CDC) Consortium of National Networks established to advance prevention efforts related to tobacco-related and cancer health disparities. With a specific focus on populations with low socioeconomic status (SES) characteristics, SMHN is jointly funded by the Division of Cancer Prevention and Control (DCPC) and Office on Smoking and Health (OSH) and is intended to complement other CDC-funded chronic disease program activities. One example of SMHN's strategic approach to address breast cancer disparities (late-stage) among female adult populations with low SES characteristics included the establishment of a SMHN Regional Resource Lead Organization (RRLO) in a non-Medicaid expansion state located within the Appalachian region. One of the SMHN Regional Resource Lead Organizations (RRLOs) is Meharry Medical College located in Nashville, Tennessee. Description of Methods or Approaches: Meharry Medical College RRLO's approach involved increased local infrastructure, capacity, and coordination through the establishment of innovative partnerships coupled with the adoption of community-based interventions and utilization of data (e.g., Geographic Information System, etc.) as well as community engagement (including a series of focus groups and roundtables). It also involved coordination among several counties to address breast cancer disparities, specifically among low-income and low-resourced women (primarily African-American). Data Summary: As a result of adopting this multifaceted approach, more than 40 organizations representing a diverse array of organizations (e.g., Breast Cancer Survivor Group, Vanderbilt-Ingram Cancer Center, Goodwill Industries, Nashville Career College, Men's Health Network, etc.) and sectors (including public health partners) committed to the development of a Multiregional Community Outreach and Engagement Plan. In addition to establishing new public-private partnerships, the initial findings from Meharry Medical College RRLO's approach resulted in the development of proposed recommendations as well as the identification of gaps, opportunities, and challenges. Conclusions: The initial results from Meharry Medical College RRLO's approach can potentially serve as a foundation and pathway for how to transform multilevel strategies into future strategic planning efforts (culturally and geographically relevant) relative to breast cancer disparities along the cancer continuum. Citation Format: Dwana “Dee” Calhoun, Patricia Matthews-Juarez. Investing in public-private partnerships to address breast cancer disparities among African-American women (low-income) within a non-Medicaid ACA expansion state and Appalachian region [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C21.

Abstract B48: Animal models in use by the NCI PREVENT Cancer Preclinical Drug Development Program

Abstract The Chemopreventive Agent Development Research Group in the Division of Cancer Prevention at the National Cancer Institute administers the PREVENT Program to facilitate the development of cancer preventive interventions, including chemical and immunologic agents, and biomarkers for potential use in clinical trials (https://prevention.cancer.gov/major-programs/prevent-cancer-preclinical). Recent technologic advances have enabled generation of newer preclinical animal models, which recapitulate the tumorigenic process of human cancers and have become the mainstay for translational research, as these models may be more likely to provide clinically translatable observations. Several carcinogen-induced rat and mouse models, along with genetically engineered mouse (GEM) and other transgenic animal models, are at the forefront of evaluating cancer-preventive efficacy of drugs and vaccines in various organ sites. A wide array of organ-specific animal cancer models is in use for agent efficacy and toxicity evaluations through the PREVENT program. Key characteristics of these animal models adopted by PREVENT studies include relevance to human cancers such as organ site pathology, involvement of genetic or carcinogenic drivers, and transformation of precursor lesions, as well as a consistent tumor burden within a well-defined time period. Examples of organ site–specific animal models employed by the PREVENT studies include GEM/transgenic models: BRCA1ex11, TgMMTV-neu, TgN(C3-1-TAg)cJeg, MMTV-PPARδ BRCA1co/co, MMTVCre+/+, p53 (breast); APCMin/+, B6-Msh2loxP/loxP,Tg(Vil-Cre), AKRMin/+, ApcMin/FCCC, PIRC (Rat) (colon); AJp53wt/A135V, Trp53F2-10/F2-10, Rb1F19/F19, Adeno-Cre, A/J-ULp53, FVB-CCSPKrasG12D, B6-CCSP-EGFRL858R (lung); Asc−/−, Nf2+/−,Cdkn2a+/− (mesothelioma); LSL-KrasG12D/+ , p48Cre/+, Pdx1Cre, Ptf1Cre, SMAD4-/-, Trp53R172H, Ptf1aCreERTM, hMuc1, LSL-KrasG12V, ROSA_rtTA, p53L/+, iKRasG12D/+ (pancreas); TRAMP, PtenKO, Ptenflox/flox.R26ERG(CreERT2) (prostate); Dicer-/-, Pten-/-, Amhr2+/-, Ad-mCherry-Cre (ovarian); and the carcinogen induced cancer models: MNU, DMBA (breast); OH-BBN (bladder); AOM (colon); NNK, B[a]p, NTCU (lung); asbestos (mesothelioma), MNU (prostate); and 4NQO (head and neck). Agents/drugs that have been or are being evaluated for cancer-preventive efficacy using these models include chemoprevention agents: A438079, AR-509, AZ10606120, Aspirin, Atorvastatin, Bazedoxifene, Bexarotene, Brevail, Budesonide, Ciclesonide, ED-71, ERB-041, Erlotinib, Gefitinib, GLG-302, Gugglesterone, GW274150, INT-747, JNJ-26070109, Lapatinib, Licofelone, LFA9, LY500307, Metformin, Naproxen, Omeprazole, Onc-201, Pioglitazone, PX-102, Rapamycin, SC144, SD-6010, ShetA2, Selumitenib, SR-3029, Sulindac, YS-121, XL-147 and YF476; and immuno-prevention vaccines (DNA, peptide, protein): Plac1, α-enolase, Neu, IGF-1R, IGFBP-2, anti-Fusobacterium nucleatum vaccine, TERT, multivalent-peptide, DLK1, KRAS, EGFR, Muc1, α-enolase, and mesothelin vaccines. Results from these studies will provide important data that will inform “go/no go” decisions in terms of advancing agents towards clinical trials targeting high-risk populations at the early stages of cancer development. Through the PREVENT program, different strategies including alternative dosing, lower dose drug combinations, and drug/vaccine combinations are being developed with the goal to minimize toxicity and improve efficacy. Importantly, the next generation of organ-site-specific inducible GEM models may allow for agent intervention at different stages of cancer development in adult animals representing human pathologies. We will present selected efficacy and mechanistic data for various chemopreventive agents/vaccines tested using these preclinical animal models. Acknowledgments: These studies have been conducted by academic/industrial contract Principal Investigators as part of the NCI PREVENT Program. Citation Format: Altaf Mohammed, Mark Steven Miller, Elizabeth Glaze, Romaine I. Fernando, Jennifer Fox, Ronald A. Lubet, Shizuko Sei, Robert H. Shoemaker. Animal models in use by the NCI PREVENT Cancer Preclinical Drug Development Program [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B48.

Cancer Prevention During Early Adulthood: Highlights From a Meeting of Experts

Using a life course approach, the Centers for Disease Control and Prevention’s Division of Cancer Prevention and Control and the National Association of Chronic Disease Directors co-hosted a 2-day meeting with 15 multidisciplinary experts to consider evidence linking factors in early adulthood to subsequent cancer risk and strategies for putting that evidence into practice to reduce cancer incidence. This paper provides an overview of key themes from those meeting discussions, drawing attention to the influence that early adulthood can have on lifetime cancer risk and potential strategies for intervention during this phase of life. A number of social, behavioral, and environmental factors during early adulthood influence cancer risk, including dietary patterns, physical inactivity, medical conditions (e.g., obesity, diabetes, viral infections), circadian rhythm disruption, chronic stress, and targeted marketing of cancer-causing products (e.g., tobacco, alcohol). Suggestions for translating research into practice are framed in the context of the four strategic directions of the National Prevention Strategy: building healthy and safe community environments; expanding quality preventive services in clinical and community settings; empowering people to make healthy choices; and eliminating health disparities. Promising strategies for prevention among young adults include collaborating with a variety of community sectors as well as mobilizing young adults to serve as advocates for change. Young adults are a heterogeneous demographic group, and targeted efforts are needed to address the unique needs of population subgroups that are often underserved and under-represented in research studies.

Traceback: A Proposed Framework to Increase Identification and Genetic Counseling of BRCA1 and BRCA2 Mutation Carriers Through Family-Based Outreach.

In May 2016, the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute, convened a workshop to discuss a conceptual framework for identifying and genetically testing previously diagnosed but unreferred patients with ovarian cancer and other unrecognized BRCA1 or BRCA2 mutation carriers to improve the detection of families at risk for breast or ovarian cancer. The concept, designated Traceback, was prompted by the recognition that although BRCA1 and BRCA2 mutations are frequent in women with ovarian cancer, many such women have not been tested, especially if their diagnosis predated changes in testing guidelines. The failure to identify mutation carriers among probands represents a lost opportunity to prevent cancer in unsuspecting relatives through risk-reduction intervention in mutation carriers and to provide appropriate reassurances to noncarriers. The Traceback program could provide an important opportunity to reach families from racial, ethnic, and socioeconomic groups who historically have not sought or been offered genetic counseling and testing and thereby contribute to a reduction in health disparities in women with germline BRCA mutations. To achieve an interdisciplinary perspective, the workshop assembled international experts in genetics, medical and gynecologic oncology, clinical psychology, epidemiology, genomics, cost-effectiveness modeling, pathology, bioethics, and patient advocacy to identify factors to consider when undertaking a Traceback program. This report highlights the workshop deliberations with the goal of stimulating research and providing a framework for pilot studies to assess the feasibility and ethical and logistical considerations related to the development of best practices for implementation of Traceback studies.

Workshop Report: Modulation of Antitumor Immune Responses by Dietary and Microbial Metabolites.

The human microbiota maintains an enormous and diverse capacity to produce a diet-dependent metabolome that impacts both host tissue and microbial community homeostasis. Recent discoveries support a growing appreciation that microbial metabolites derived from bioactive foods are also important regulators of host immune and metabolic functions. To gain a better understanding of the current evidence for the roles of dietary and microbial metabolites in tumor immunity, the Division of Cancer Biology and the Division of Cancer Prevention, National Cancer Institute, cosponsored a workshop on August 31 and September 1, 2016, in Bethesda, Maryland. Workshop participants examined several lines of converging science that link nutrition, microbiology, and tumor immunology and identified key concepts and research opportunities that will accelerate our understanding of these interactions. In addition, the participants identified some of the critical gaps and research challenges that could be addressed through interdisciplinary collaborations, including future opportunities for translating new information into novel cancer prevention and treatment strategies based on targeting host immune functions that are altered by metabolite sensing pathways.