Cancer Stem Cell Research: May Be The Link To Why Cancer Reoccurs
One of the greatest challenges in veterinary oncology (and human oncology) is experiencing successful treatment outcomes and finding out some time later that the cancer returns or a different cancer appears.
Depending on the type of cancer, recurrence rates in dogs and cats treated with conventional therapies (surgery, chemo and radiation) can vary considerably. For example:
- Mast cell tumors may recur in approximately 20–50% of cases, depending on tumor grade, surgical margins and biological behavior.
- Soft tissue sarcomas have reported local recurrence rates ranging from 7–75%, largely influenced by tumor grade and the completeness of surgical removal.
- Osteosarcoma has a high likelihood of metastatic recurrence, with more than 90% of dogs developing metastatic disease if treated with surgery alone.
- Hemangiosarcoma is also associated with a high recurrence rate because microscopic metastatic disease is often present before diagnosis.
- Lymphoma, while frequently achieving remission with chemotherapy, commonly relapses, with many dogs experiencing recurrence within months after completing treatment.
It is important to recognize that cancer is not a single disease and every tumor behaves differently.
One area receiving increasing attention is the study of cancer stem cells. I recently read an excellent article by my friend and respected researcher, Sylvie Beljanski, whose work explores the potential role these specialized cells may play in cancer progression and recurrence.
Cancer stem cells represent a relatively small population of cells within some tumors that appear to behave differently from the majority of cancer cells. Laboratory studies suggest they may have the ability to:
- Self-renew
- Remain dormant for extended periods
- Resist certain therapies
- Generate new tumor cells under appropriate conditions
One way to think about cancer stem cells is to imagine a garden.
Removing a visible weed eliminates what you can see above the soil. However, if seeds remain in the ground, new weeds may eventually appear if the conditions (the terrain) that encouraged the growth remain.
If the biological terrain that allowed the cancer to develop remains unchanged, residual cancer stem cells may persist. The terrain is influenced by genetics (5% of dis-ease expression comes from gene expression) and epigenetics (95% of dis-ease expression comes from environmental influences). Though we can not change the genes, we can change the epigenetic influences, creating conditions that are not favorable for renewed tumor growth or recurrence.
The Tumor Microenvironment
Scientists now recognize that the environment surrounding cancer cells, often referred to as the tumor microenvironment, can influence how cancers grow, spread and respond to treatment. This concept has become one of the most active areas of cancer research in both human and veterinary medicine.
In integrative veterinary medicine, we often discuss the broader concept of the body’s biological terrain. While terminology may differ, both perspectives recognize that factors throughout the body can influence overall health and disease processes.
Areas that continue to receive scientific attention include:
- Nutrition and metabolic health
- Immune system function
- Chronic inflammation
- Oxidative stress
- Oxygen delivery to tissues
- The gut microbiome
- Environmental exposures
- Cellular energy production
The emotional environment and the human-animal bond – Research continues to explore the effects of stress, emotional state and belief systems on physiology, immune regulation, and healing. In companion animals, there is growing interest in how pets may become physiologically and behaviorally attuned to the emotional state of their caregivers through processes such as emotional contagion and entrainment, making the well-being of both the pet and the pet parent an important consideration.
These factors do not necessarily cause or prevent cancer on their own. Rather, researchers are working to better understand how they may influence disease progression, treatment response and long-term health.
One of the most fascinating aspects of oncology is that two pets with the same diagnosis may experience very different outcomes.
Age, genetics, tumor biology, overall health, immune function, nutrition, environmental exposures and many other variables can all influence how a patient responds to treatment. Consequently, appropriate diagnostics and individualized treatment plans have become increasingly important in both conventional and integrative cancer care.
Emerging Areas Of Research
Sylvie Beljanski also discussed research supported by The Beljanski Foundation examining naturally derived compounds such as Pao Pereira and Rauwolfia vomitoria.
Early laboratory studies suggest these botanicals may influence biological pathways associated with cancer stem cells, including those involved in self-renewal and metastatic potential. Although these findings are encouraging, additional preclinical and clinical research is needed before the role of these botanicals in veterinary cancer care can be fully understood. Pasco Veterinary Medical Center is privileged to participate in ongoing clinical research evaluating these botanicals in canine cancer patients, with study products provided for eligible cases. This reflects a broader trend in oncology: researchers are increasingly exploring therapies that target not only the visible tumor, but also the biological mechanisms that contribute to recurrence.
An Integrative Perspective
In my practice, cancer care is not focused on a single treatment. Instead, it involves developing a comprehensive plan tailored to each patient.
Depending on the individual case, this begins with appropriate diagnostics to fully characterize the disease and identify underlying factors that may influence healing. This may include evaluating nutrient deficiencies, toxic burdens, metabolic imbalances, microbiome health, immune function, and other comorbidities that can affect the patient’s overall health and response to treatment.
Based on these findings, treatment may include surgery, targeted nutritional support, immune modulation, photodynamic therapy, hyperbaric oxygen therapy, ozone therapy, targeted chemotherapy based on gene mutations, and many other supportive approaches. The goal is to improve quality of life while supporting the patient throughout treatment and recovery, while addressing the underlying terrain that influences long-term health.
As our understanding of cancer biology continues to evolve, it is becoming increasingly clear that successful cancer management involves more than reducing tumor size alone. Long-term outcomes may also depend on understanding the complex interactions between tumor biology, the immune system, metabolism and the body’s internal environment (the terrain) and our emotions/belief systems.
Cancer stem cell research represents one of many exciting areas that may help us better understand why some cancers return and how future therapies may continue to improve outcomes for both people and pets.
As always, continued research will be essential to translating these discoveries into safe, effective and affordable treatments that benefit our patients.
FurEver Grateful,
Dr. Marlene Siegel
Inspired by the work of Sylvie Beljanski and the ongoing research supported by The Beljanski Foundation.
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Read MoreSources:
- Mast cell tumors may recur in approximately 20–50% of cases, depending on tumor grade, surgical margins, location, and biological behavior.
Citations:- Blackwood L, Murphy S, Buracco P, et al. European consensus document on mast cell tumours in dogs and cats. Veterinary and Comparative Oncology. 2012;10(3):e1-e29.
- Kiupel M, Webster JD, Bailey KL, et al. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors. Veterinary Pathology. 2011;48(1):147-155.
- Soft tissue sarcomas have reported local recurrence rates ranging from approximately 7–75%, largely influenced by tumor grade, tumor location, and the completeness of surgical excision.
Citations:- Bray JP, Polton GA, McSporran KD, Bridges JP, Whitbread TM. Canine soft tissue sarcoma managed with marginal excision: recurrence, metastasis and survival. Journal of Small Animal Practice. 2014;55(12):627-631.
- Dernell WS, Withrow SJ, Kuntz CA, Powers BE. Principles of treatment for soft tissue sarcoma. Clinical Techniques in Small Animal Practice. 1998;13(1):59-64.
- Osteosarcoma has a very high likelihood of metastatic recurrence, with more than 90% of dogs developing metastatic disease if treated with surgery alone, indicating that microscopic metastases are usually present at diagnosis.
Citations:- Withrow SJ, Powers BE, Straw RC, Wilkins RM. Comparative aspects of osteosarcoma. Dog versus man. Clinical Orthopaedics and Related Research. 1991;(270):159-168.
- Boston SE, Ehrhart NP, Dernell WS, et al. Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment. Journal of the American Veterinary Medical Association. 2006;228(12):1905-1908.
- Hemangiosarcoma is associated with a high recurrence rate and rapid metastatic progression because microscopic metastatic disease is frequently present before the primary tumor is detected.
Citations:- Clifford CA, Mackin AJ, Henry CJ. Treatment of canine hemangiosarcoma: 2000 and beyond. Journal of Veterinary Internal Medicine. 2000;14(5):479-485.
- Brown NO, Patnaik AK, MacEwen EG. Canine hemangiosarcoma: retrospective analysis of 104 cases. Journal of the American Veterinary Medical Association. 1985;186(1):56-58.
- Lymphoma, while often achieving remission with chemotherapy, commonly relapses, with many dogs experiencing recurrence within months after completing treatment.
Citations:- Vail DM, Pinkerton ME, Young KM. Canine lymphoma and lymphoid leukemias. In: Withrow & MacEwen’s Small Animal Clinical Oncology. 6th ed. Elsevier; 2020.
- Garrett LD, Thamm DH, Chun R, Dudley R, Vail DM. Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma. Journal of Veterinary Internal Medicine. 2002;16(6):704-709.
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