The goal for this project is to develop a reliable, accessible, and actionable test to identify dogs at risk for hemangiosarcoma during the earliest stages of disease and to use a strategic, rationally designed approach to prevent its occurrence in these high-risk dogs before it becomes clinically detrimental and life-threatening. The study has two objectives. The first is to determine the most reasonable duration of an SOS test result. In other words, how long can a low-risk SOS test result be trusted and how much time might elapse between a high-risk SOS test result and the development of hemangiosarcoma. The second aim is to continue periodic testing for dogs previously enrolled in the Shine On study whose test result would have placed them in a high-risk category for development of hemangiosarcoma, and to provide eBAT as a strategy for prevention.
To complete the first objective, we conducted surveys to determine the health status of every dog enrolled in Shine On phase-3 (SO3, the early detection phase) at 6-month intervals.
To complete the second objective, we finalized the analysis of the data from Shine On phase-1 (SO1) (used as the “training set” for SOS test) and applied those results to dogs from SO3 to select candidates for continued, periodic testing. We enrolled almost 70 dogs into the Shine On continuation phase (SOC). Owners of dogs that were assigned to the high-risk category were given information about available screening, the opportunity for their dogs to complete screening, and if eligible, to enroll in eBAT prevention. We have screened 40 dogs. The original intent was to enroll 12 dogs in the interception arm of the study. Based on our promising data, we increased the size of this group to enroll up to 20 dogs. Thirteen have enrolled and received eBAT uneventfully; three are scheduled for screening; and the remainder are being recruited from a pool of applicants that have passed the initial screens. At this point, additional enrollments are on hold and the costs are being borne through discretionary sources available to the investigators (individual donations to the project) Sixteen have been eligible for eBAT prevention. The emerging data are extremely encouraging, suggesting that dogs receiving eBAT interception have approximately 4-fold lower risk of developing cancer than dogs assigned to the high-risk group that did not receive eBAT in the SO3 phase.
The project has also been extremely successful in training the next generation of researchers with specific interest in canine health.
Publications: Grant Number: 2806-MOU Principal Investigator: Modiano, Jaime F Date: 03/07/2025 Sarver AL, Makielski KM, DePauw TA, Schulte AJ, Modiano JF. (2022). Increased risk of cancer in dogs and humans: a consequence of recent extension of lifespan beyond evolutionarily determined limitations? (Perspective). Aging and Cancer, 3(1), 3-19. PMID: 35993010. PMCID: PMC9387675
Dicovitsky R, Schappa JT, Schulte AJ, Lang HP, Kuerbitz E, Roberts S, DePauw T, Lewellen M, Winter AL, Stuebner K, Buettner M, Reid K, Bergsrud K, Pracht S, Chehadeh A, Feiock C, O’Sullivan GO, Carlson T, Armstrong AR, Meritet D, Henson MS, Weigel BJ, Modiano JF, Borgatti A, Vallera DA. (2024). Toxicity profile of eBAT, a bispecific ligand targeted toxin directed to EGFR and uPAR, in mice and a clinical dog model. Toxins, 16, 376. doi.org/10.3390/toxins16090376
DePauw TA, Schulte AJ, Khammanivong A, Dicovitsky R, Lewellen M, Stuebner KM, Winter AL, Burt LE, Bergsrud K, Pracht S, Ober C, Anderson KL, Nell E, Sarver AL, Kim JH, Henson MS, Dickerson EB, Borgatti A, Vallera DA, Cutter GR, Modiano JF. Impact of Breed (Ancestry) and Age in Cancer Risk Assessment and Interception in a Prospective Cohort of Companion Dogs: A Feasibility Study. Manuscript in preparation.
Li T, Khammanivong A, DePauw TA, Schulte AJ, Modiano JF. Liquid biopsy testing to monitor remission and anticipate relapse of canine hemangiosarcoma. Manuscript in preparation. DePauw TA, Schulte AJ, Khammanivong A, Lewellen M, Stuebner KM, Luethke R, Winter AL, Burt LE, Bergsrud K, Pracht S, Sarver AL, Kim JH, Henson MS, Dickerson EB, Borgatti A, Spector LG, Vallera DA, Cutter GR, Modiano JF. Lifespan and cancer risk differences in boxers golden retrievers and Portuguese Water Dogs: a prospective cohort study. Manuscript in preparation.
Presentations:
DePauw TA, Khammanivong A, Modiano JF. (2020). Machine Learning for Early Detection of Hemangiosarcoma. Annual Meeting of the Veterinary Cancer Society, Oct. 15-17, 2020 (Conference was conducted virtually due to COVID-19). Abstract was selected for an oral platform presentation by Ms. Taylor DePauw
Modiano JF, DePauw TA, Khammanivong A, Schulte AJ, Winter AL, Kim JH, Stuebner K, Fahrenkrug AM, Vallera DA, Borgatti A, Dickerson EB, Henson MS. (2020). Early detection for strategic prevention of a terminal canine cancer: A model to reduce the impact of cancer in our society. (Abstract 4592, presented in pre-recorded format in the virtual poster session). Annual Meeting of the American Association for Cancer Research, April 27-29, 2020 (Conference was conducted virtually due to COVID-19)
DePauw T, Khammanivong A, Lewellen M, Schulte A, Kim JH, Winter AL, Bergsrud K, Chehade A, Pracht S, Stuebner KM, Daniel J, Wolf-Ringwall A, Husbands B, Henson MS, Dickerson EB, Cutter GR, Vallera DA, Borgatti A, Modiano JF. (2021). The Shine On Program for Early Detection and Prevention of Canine Hemangiosarcoma (presented in pre-recorded format in the virtual poster session). Annual Meeting of the Veterinary Cancer Society, Nov. 4-7, 2021 (Conference was conducted virtually due to COVID-19)
Modiano JF. (2021). Cellular Origin and Molecular Vulnerabilities of Canine Hemangiosarcoma – the Next Chapter in Treatment and Prevention (oral platform presentation in the hemangiosarcoma session Page 25 Grant Number: 2806-MOU Principal Investigator: Modiano, Jaime F Date: 03/07/2025 chaired by Dr. Modiano). Annual Meeting of the Veterinary Cancer Society, Nov. 4-7, 2021 (Conference was conducted virtually due to COVID-19)
Modiano JF. (2021). Early Detection and Strategic Prevention of Canine Hemangiosarcoma: An Update on the Shine-On Project (live webinar). A free University of Minnesota/Animal Cancer Care and Research Program Webinar, November 9, 2021 (virtual lecture)
Modiano JF. (2021). Changing Our Approach to Cancer: Why Cancer Happens and How Early Detection and Strategic Prevention Will Help Us Defeat It (in-person presentation). Fetch DVM360 Conference. December 4, 2021, San Diego, CA 2021
Modiano JF. (2021). How We Can Change the Cancer Landscape (in-person presentation). Fetch DVM360 Conference. December 5, 2021, San Diego, CA 2021
Modiano JF. (2021). Changing the Face of Cancer through Effective Prevention (in-person presentation). Fetch DVM360 Conference. December 5, 2021, San Diego, CA 2021
Modiano JF. (2021). What Is New, Exciting, and Encouraging in Canine Hemangiosarcoma? (In-person presentation) Fetch DVM360 Conference. December 5, 2021, San Diego, CA 2021
Modiano JF. (2021). One Pathologist’s Dream: Detecting Cancer Before It Starts and Killing It Before It Forms (virtual, live seminar). Department of Laboratory Medicine and Pathology Grand Rounds, University of Minnesota School of Medicine, December 2, 2021, Minneapolis, MN
Modiano JF. (2022). The Apparent Cancer Epidemic: Why is cancer so common in dogs and humans? (Virtual live lecture)Minnesota Dog Breeders Association Annual Meeting, February 6, 2022
Modiano JF. (2022). Demystifying Cancer: Why cancer happens and what we can do about it (virtual live lecture). American Association of University Women Seminar Series, February 7, 2022
Dicovitsky, R (2022). Shine-On Prevention of Canine Hemangiosarcoma: Lifetime Follow-up (virtual live seminar). Department of Veterinary Clinical Sciences Grand Rounds, University of Minnesota College of Veterinary Medicine February 24, 2022, Minneapolis, MN
Modiano JF. (2022). The Minnesota Solution to Cancer: Find It Before It Starts; Kill It Before It Forms (virtual live seminar). Hormel Institute Seminar Series, March 2, 2022, Austin, MN
Modiano JF. (2022). Why Cancer Happens: A Story of Success and Unintended Consequences (virtual live seminar). Australia and New Zealand College of Veterinary Scientists Science Week 2022, June 25, 2022, The Star, Broadbeach, Queensland, Australia
Modiano JF. (2022). Reducing the Impact of Cancer on our Society through Risk Assessment and Strategic Prevention (virtual live seminar). Australia and New Zealand College of Veterinary Scientists Science Week 2022, June 25, 2022, The Star, Broadbeach, Queensland, Australia
Modiano JF. (2022). Taming Canine Hemangiosarcoma: New, Exciting, and Encouraging Developments in Our Ability to Manage a Dreadful Cancer (virtual live seminar). Australia and New Zealand College of Veterinary Scientists Science Week 2022, June 25, 2022, The Star, Broadbeach, Queensland, Australia
Li T, Khammanivong A, DePauw T, Schulte A, Modiano J. (2022). Monitoring Hemangiosarcoma Treatment Success with A Peripheral Blood Test (in-person poster presentation). National Veterinary Summer Scholars Symposium, August 4-6, 2022, Minneapolis, MN
Modiano JF. (2022). Comparative Oncology: Challenges and Opportunities for the Coming Decade. Oncology Breakout Session (in-person seminar). National Veterinary Summer Scholars’ Symposium, August 5, 2022, St. Paul, MN
Modiano JF. (2022). Risk Assessment for Cancer – Find It Before It’s there, Kill it Before It Forms (virtual live seminar). Department of Veterinary Clinical Sciences Grand Rounds, University of Minnesota College of Veterinary Medicine, September 22, 2022, St. Paul, MN
Modiano JF. (2022). Principles of Cancer Immunotherapy (virtual recorded lecture). The Science of Veterinary Oncology Lecture Series, American College of Veterinary Internal Medicine, an Online Resource, 2022
Modiano JF. (2022). Burn Down the Mission – Creating an Inhospitable Environment to Improve Cancer Outcomes. RAR Seminar Series, University of Minnesota, September 30, 2022, Minneapolis, MN
Modiano JF. (2022). Two+ Decades of Progress on Canine Hemangiosarcoma (virtual live presentation, also available on YouTube as Ottertalk #25). Otterhound Club of America Ottertalk, November 1, 2022
Modiano JF, Schulte AJ, DePauw TA, Khammanivong A, Kim JH, Sarver AL, Cutter GR, Lindquist E, Makielski KM. (2022). Identification and characterization of the cancer permissive environment in companion dogs (in-person poster presentation and invited oral platform presentation). Inaugural AACR Aging and Cancer Meeting, November 17-20, 2022, San Diego, CA
Modiano JF. (2022). What is Hemangiosarcoma Anyway? (Virtual live presentation) UC Davis Veterinary Student Rounds, December 18, 2022
Borgatti A, Dickerson EB, Modiano JF, Diehl K. (2022). New Thoughts on Hemangiosarcoma in Dogs (pre-recorded podcast). Fresh Scoop Podcast (#52), Morris Animal Foundation, December 20, 2022
Modiano JF, Dickerson EB, Borgatti A. (2023). What Do We Really Know About Canine Hemangiosarcoma?” Veterinary Cancer Society Oncology Connections, May 9, 2023
Modiano JF. (2023). Liquid Biopsies in Diagnostic Pathology: A Brief History and Current and Future Applications. Keynote Address: Annual Meeting of the European Society of Veterinary Oncology (ESVONC), Alicante, Spain, May 27, 2023
Modiano JF. (2023). Defining the Cancer Permissive Environment and Its Applications in Early Detection, Risk Assessment, and Strategic Prevention of Cancer. Annual Meeting of the European Society of Veterinary Oncology (ESVONC), Alicante, Spain, May 27, 2023
Kappenman I, Spielman R, Modiano J, Schulte A. (2023). Optimizing flow cytometry antibody panel for the Shine On Suspicion project protocol. National Veterinary Scholars Symposium, San Juan, PR, August 3-5, 2023
Spielman R, Kappenman I, Modiano J, Schulte A. (2023). Optimizing lysis of canine red blood cells for flow cytometry. National Veterinary Scholars Symposium, San Juan, PR, August 3-5, 2023
Schulte AJ, DePauw TA, Khammanivong A, Winter AL, Stuebner K, Kappenman I, Spielman R, Burt LE, Lewellen M, Borgatti A, Feiock C, Dicovitsky R, Henson MS, Dickerson EB, Chehadeh A, Pracht S, Bergsrud K, Reid K, Espejo-Freire A, Murugan P, Linden MA, Cutter GR, Weigel BJ, Sarver AL, Vallera DA, Modiano JF. (2023). Optimization and translation of a flow cytometry protocol for cancer risk prediction in dogs. Masonic Cancer Center Research Symposium, October 30, 2023, Minneapolis, MN
Modiano JF. (2024). “Cambiando Nuestro Enfoque del Cáncer: Porqué Ocurre el Cáncer y Como la Detección Temprana y la Prevención Estratégica Nos Ayudarán a Derrotarlo” (Changing Our Approach to Cancer: Why Cancer Happens and How Early Detection and Strategic Prevention Will Help Us Defeat It”), 3-hours of lecture at the SLOVET (Sociedad Latinoamericana de Oncologia Veterinaria) Virtual Meeting (Mexico), January 20, 2024
Makielski KM and Modiano JF. (2024). Liquid Biopsies for Cancer Detection: Are We Pawsitive We Know What We Are Doing? Annual Meeting of the Minnesota Veterinary Medical Association, Minneapolis, MN, February 8, 2024
Makielski KM and Modiano JF. (2024). Liquid Biopsies in Veterinary Medicine. Annual Meeting of the Minnesota Association of Veterinary Technicians, Minneapolis, MN, February 9, 2024
Modiano J (2024). From Furry Friends to Fossil Giants: What We Can Learn by Studying Cancer across the History of Life on Earth.” The Animal Health Education Series, University of Minnesota College of Veterinary Medicine, St. Paul, MN, February 6, 2024
Modiano JF. (2024). What Do We Really Know about Canine Hemangiosarcoma? Italian Society for Vet Oncology Hemangiosarcoma Symposium (virtual event), February 10, 2024
Modiano J. (2024). Early Detection, Risk Assessment and Strategic Prevention: A New Recipe to Manage Hemangiosarcoma and Other Life-Threatening Cancers. Italian Society for Vet Oncology Hemangiosarcoma Symposium (virtual event), February 10, 2024
Modiano JF, Schulte AJ, Dicovitsky R, DePauw TA, Khammanivong A, Lewellen M, Burt LE, Vallera DA, Cutter GR, Winter AL, Stuebner KM, Chehadeh A, Pracht S, Borgatti A, Henson MS, Dickerson EB, Ober C, Anderson KL, Nell E, Sarver AL. (2024). Risk assessment, early detection, and strategic prevention of naturally occurring cancers in companion dogs (Abstract 5176). Annual Meeting of the American Association for Cancer Research, San Diego, CA, April 5-10, 2024
Modiano J. (2024). Evolution, Aging, and Cancer: How Dogs can Help Us Understand and Manage the Perceived Cancer Epidemic. Invited platform presentation for the Educational Session on Spontaneous Cancers of Companion Animals as Clinically Relevant Models for Advancing Human Oncology. Annual Meeting of the American Association for Cancer Research, San Diego, CA, April 6, 2024
Modiano j. (2024). What Animals Can Teach Us. Breakout Session – One Health: People, Animals, and the Planet. Joint presentation with Barbara Natterson-Horowitz and Samuel Ramsey moderated by Nicholas St. Fleur. Aspen Ideas Health, Aspen, CO, June 22, 2024
Schulte AJ, DePauw TA, Khammanivong A, Lewellen M, Burt L, Dicovitsky R, Winter AL, Stuebner KM, Chehadeh A, Pracht S, Ober C, Anderson KL, Esther N, Borgatti A, Henson MS, Dickerson EB, Sarver AL, Vallera DA, Cutter GR, Modiano JF. (2024). Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs (Abstract A066). American Association for Cancer Research Special Conference in Cancer Research: Liquid Biopsy: From Discovery to Clinical Implementation, San Diego, CA, November 13-16, 2024
Schulte AJ, Dicovitsky R, DePauw TA, Winter AL, Stuebner KL, Chehadeh A, Pracht S, Borgatti A, Khammanivong A, Lewellen M, Burt LE, Vallera DA, Henson MS, Dickerson EB, Ober C, Anderson KL, Nell E, Sarver AL, Cutter GR, Modiano JF. (2025). Active interception to modulate the systemic cancerpermissive microenvironment and reduce cancer incidence in companion dogs with elevated cancer risk. (Abstract 7495). Annual Meeting of the American Association for Cancer Research, Chicago, IL, April 25-30, 2025
No Cost Extension Request: N/A
Requests for CHF Assistance: N/A
Literature Cited:
Sarver, A. L., Makielski, K. M., DePauw, T. A., Schulte, A. J. & Modiano, J. F. Increased risk of cancer in dogs and humans: a consequence of recent extension of lifespan beyond evolutionarily-determined limitations? Aging Cancer 3, 3-19, doi:10.1002/aac2.12046 (2022).
Nam, Y. et al. Dog size and patterns of disease history across the canine age spectrum: Results from the Dog Aging Project. PLoS One 19, e0295840, doi:10.1371/journal.pone.0295840 (2024).
Rozhok, A. & DeGregori, J. A generalized theory of age-dependent carcinogenesis. Elife 8, doi:10.7554/eLife.39950 (2019).
Rozhok, A. I. & DeGregori, J. The evolution of lifespan and age-dependent cancer risk. Trends Cancer 2, 552-560, doi:10.1016/j.trecan.2016.09.004 (2016).
Kent, M. S., Burton, J. H., Dank, G., Bannasch, D. L. & Rebhun, R. B. Association of cancerrelated mortality, age and gonadectomy in golden retriever dogs at a veterinary academic center (1989-2016). PLoS One 13, e0192578, doi:10.1371/journal.pone.0192578 (2018).
Cooley, D. M., Schlittler, D. L., Glickman, L. T., Hayek, M. & Waters, D. J. Exceptional longevity in pet dogs is accompanied by cancer resistance and delayed onset of major diseases. J Gerontol A Biol Sci Med Sci 58, B1078-1084, doi:10.1093/gerona/58.12.b1078 (2003).
Zhuang, X. et al. Aging limits stemness and tumorigenesis in the lung by reprogramming iron homeostasis. bioRxiv, doi:10.1101/2024.06.23.600305 (2024).
Shuldiner, E. G. et al. Aging represses lung tumorigenesis and alters tumor suppression. bioRxiv, doi:10.1101/2024.05.28.596319 (2024).
Labadie, J. et al. Cohort profile: The Golden Retriever Lifetime Study (GRLS). PLoS One 17, e0269425, doi:10.1371/journal.pone.0269425 (2022).
Club, A. B. Health Survey Report. (http://americanboxerclub.org/ABC-Health-Report-Aug2012.pdf, 2012). Glickman, L., Glickman, N. & Thorpe, R. The Golden Retriever Club of America National Health Survey, <http://www.grca.org/healthsurvey.pdf> (2000). 12 13
Slater, M. The 2005 Portuguese Water Dog Health Survey: Final Report, <http://www.pwdca.org/health/surveys/2005/2005PWDHealthSurveyReport.pdf> (2006).
Kim, J. H. et al. Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion. Cancer Res Commun 4, 1467-1480, doi:10.1158/2767-9764.CRC-23-0441 (2024).