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January 2005 Newsletter of the Canine Cancer Program at AMC and the University of Colorado Health Sciences Center Download a PDF version of this page here.
NewsAnother Rocky Mountain winter has brought forth
a New Year. We hope it is healthy and happy for all! It is hard to believe that it has been almost two years since the Modiano lab at AMC joined the Integrated Department of Immunology at the University of Colorado Health Sciences Center (UCHSC) and National Jewish Medical and Research Center. Although the details of the affiliation continue to be negotiated, our lab has benefited greatly from the joint association with AMC and UCHSC. It has allowed us to solidify existing collaborations, begin new ones, and has provided us improved access to the resources available through the University of Colorado Cancer Center (the only National Cancer Institute designated comprehensive cancer center in the Rocky Mountain Region). This year saw the departure of Dr. Ashley Frazer-Abel, who left the lab after 4 years to take a position as Instructor in the Department of Medicine at UCHSC. Dr. Angela Lamerato joined our program in the summer as a post-doctoral fellow to work on cancer immunotherapy and canine hemangiosarcoma. It is safe to say that 2004 was a banner year for canine health research. This year saw the completion of the canine genome sequence and several important papers that defined evolutionary relationships among dog breeds. This new information will provide unique resources to define the significance of heritable risk factors in cancer. Through the collaborations we have forged, we anticipate continued progress and new discoveries that will be useful in our fight to prevent and treat cancer in dogs and people. As always, we thank all of you who have contributed to our studies financially, and by allowing your pets to participate. Your support makes our work possible. Sincerely, New and Ongoing StudiesFunds from the “Cancer Initiative” of the AKC
Canine Health Foundation have supported the research
project “Heritable and Sporadic Genetic Lesions
in Canine Lymphoma and Osteosarcoma” (AKC CHF
Grant 2254) since 2002. This collaborative project
between our lab and Dr. Matthew Breen’s group at
North Carolina State University seeks to determine how
genes impact the development and behavior of
lymphoma and bone cancer in dogs.
We have renewed our efforts to understand the
genetics of canine hemangiosarcoma and to develop
improved methods for diagnosis and treatment. This
project will continue with new anticipated funding from
the AKC Canine Health Foundation (“Tailored
Antitumor Vaccines for Canine Hemangiosarcoma”).
We also await news on funding decisions for various
grant applications to other agencies. For eligibility
criteria and recruitment details about ongoing studies,
please contact Dr. Modiano by electronic mail or by
telephone. Updated details about every facet of our
research programs will be available on our lab web site,
which should up and running this spring. Research Progress: Bone CancerOsteosarcoma is the most common type of primary
bone cancer in dogs accounting for up to 85% of tumors
that originate in the skeletal system. It is estimated that at
least 6,000 new cases, and perhaps even more than 8,000,
are diagnosed in dogs each year in the United States.
Osteosarcomas are seen most often in the appendicular
skeleton (long bones of the limbs), most often “near the
knee” and “away from the elbow.” However, these
tumors can also affect the axial skeleton (cranium, spinal
column, ribs). Large and giant breed dogs are at higher
risk for bone cancer, especially of the long bones. For
example, it is estimated that the relative risk to develop
this disease in giant breeds such as Scottish Deerhounds
and Great Danes may be as much as 200-times higher
than in small and toy breeds. Among dogs at high risk, we
also include Rottweilers, Great Pyrenees, Greyhounds,
Mastiffs, and others. The disease usually becomes evident during middle age (~7-10 yr), although bone cancer can affect dogs under 1 year of age. We believe that the first series of genetic changes (mutations) that lead to malignant transformation of bone cells occur early in life, when cell division is ongoing at a rapid pace in the growth plates of the long bones. These changes are sufficient to provide the affected cells with a growth advantage in their environment, but additional mutations are necessary to produce clinical disease. Therefore, the disease is “dormant” until the accumulation of mutations leads to a “crisis” where cells undergo uncontrolled proliferation. The age when the disease becomes evident in any individual, thus, will depend on that individual’s predisposition for mutations and the rate at which they accumulate until the “crisis” stage is reached. Most of the mutations are probably secondary to errors that occur during the normal process of cell division, but heritable factors may influence the number and type of mutations seen, accounting for differences in risk among breeds that are more susceptible to the disease simply because their bone cells must divide more to attain a large bone size. Factors that affect growth rate, such as diets that promote rapid growth in puppies, may also influence risk (or the rate at which mutations accumulate). Bone cancer also happens in people, primarily in children and adolescents under 20 years old, although it is less common than in dogs (approximately 2,500 to 3,000 new cases are diagnosed yearly in the United States). Given the genetic similarities and the shared environment between dogs and people, it is perhaps not surprising that bone tumors share genetic and biochemical defects that contribute to the origin and progression of the disease in both species. The treatment for bone cancer is similar in dogs and in children. The tumors are very aggressive and metastatic, so it is a fair assumption that at the time of diagnosis the disease will have already spread beyond the primary site. For this reason, the standard-of-care for bone cancer includes surgery to remove the primary tumor, followed by adjuvant chemotherapy to attack the cells that have left the site. In dogs, approximately 50% survive one year with standard-of-care, less than 30% survive 2 years, and less than 10% reach 3 years. These statistics are tempered when we consider that one year is approximately 10% of a canine lifetime; however, we feel that new therapies designed to exploit the genetic and biochemical abnormalities of the tumors will help us improve the outcome of dogs with this disease. Through our ongoing studies, we have developed a
large bank of resources that will help improve our
understanding of bone cancer. Our work with Dr. Breen
and new data from Dr. Cheryl London at the University
of California, Davis may allow us to define genetic
abnormalities that are peculiar to specific breeds. We
similarly look forward to working with Dr. Kerstin
Lindblad-Toh (Broad institute, MIT) and Dr. Kenine
Comstock (University of Michigan) in their newly
funded project that seeks to map heritable risk factors
for bone cancer in Rottweilers and other dog breeds.
Finally, we are continuing research with Dr. Susan
Lana and Dr. Nicole Ehrhart of the Colorado State
University Animal Cancer Center to develop novel
treatment options for bone cancer using gene therapy,
which we hope will improve survival for dogs and
people affected with this disease. Research Progress: HemangiosarcomaCanine hemangiosarcoma is an incurable tumor of cells that line blood vessels. Based on current estimates of the lifetime risk of cancer in dogs and the prevalence of hemangiosarcoma, we predict that of 65 million pet dogs living in the United States today, as many as two million may get this cancer and die from it. Although dogs of any age and breed are susceptible to hemangiosarcoma, it occurs more commonly in dogs beyond middle age, and in breeds such as Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, and Skye Terriers, among others. Hemangiosarcoma is extremely indolent – that is, it develops slowly and is essentially painless – so clinical signs are usually not evident until the advanced stages when the tumors are resistant to most treatments. Less than 50% of dogs treated with standard-of-care of care for this tumor (surgery and intensive chemotherapy) survive more than six months. Many dogs die from severe internal bleeding before there is an opportunity to institute treatment. When we consider the severity of this disease and the lack of effective treatment options, it is easy to see how methods for early detection would be useful. Early detection might improve the outcome of dogs treated with standard-of-care, but also allow us to design novel treatment options that have better odds of eradicating the tumor. We recently published a method that improves our ability to diagnose hemangiosarcoma in tissue biopsies. Based on this, we have pursued development of a blood test that will provide early detection of canine hemangiosarcoma in dogs at risk (application No. 60/608,745 submitted to the U.S. Patent Office). Although the test still requires further refinement, our results to date are encouraging and we hope that it will soon be available for use by practicing veterinarians. An advantage
of early diagnosis is that tumors at this stage are more amenable to
treatment. A newly approved research project, which will be conducted in
collaboration with Dr. Donald Bellgrau and Dr. Jill
Slansky at UCHSC, will seek to develop customized
tumor vaccines to treat dogs with hemangiosarcoma that
are diagnosed in the early stages of the disease. Research Progress: LymphomaWe previously dedicated a research focus to canine
lymphoma. Many of our colleagues and supporters have
had to deal with this disease first hand, and so recognize
its severe consequences. Even since then, there has been
significant progress in our understanding of this
disease, or rather, group of diseases. We also have shown that the rates of B cell lymphoma and T cell lymphoma (these are tumors derived from “T cells” or cells that are in charge of regulating the immune system and killing infected or abnormal cells) differ among various dog breeds. An interesting observation is that there appear to be shared heritable risk factors for some types of lymphoma that may predate the development of modern breeds; and then there appear to be heritable or breed-specific risk factors for other types of lymphoma that may have been acquired during the process of breed development. Finally, as part of our work with Dr. Breen, we
have shown that canine lymphomas share various
genetic and biochemical features with their human
counterparts, offering new evidence that diseases that
afflict us and our dogs have common evolutionary
roots. Thanks to ContributorsWe are grateful to the agencies, foundations, and individuals who have sponsored our work: 2005
2004
2003
2002
Colorful CaninesWe want to introduce you to two special dogs. They are special as every
dog is to their family, but they are also
special because of the lessons we can learn from them. Willie and Nathan
are cancer survivors, but they don’t know
that. All they know is that the sun rises in the morning and they get
to be with the people they love, and cancer did
not change that for them. The same is true for their families. Remissions
are never predictable, so they have learned
to live each day to its fullest potential and to take nothing for granted.
Meanwhile, we continue to learn from Willie
and Nathan. What is it that made them respond favorably to their treatments,
when other dogs do not? What is it
about them, their environment, their treatment, and their lifestyle that
has led them to enjoy a high quality of life
with their disease? These are some of the questions we hope to answer
with our research as we strive to help other
families deal with cancer in their midst. Meet WillieThere is only one-way to describe Willie: Willie is a Golden! Willie has multiple AKC, UKC, and USDAA agility titles, including an Excellent Jumpers title and a Master Agility Excellent title that he earned with his 10th qualifying perfect score less than a month after his initial diagnosis. Despite having little formal field training, Willie has always loved to retrieve birds. He has earned an AKC Junior Hunter title and several Golden Retriever Club of America Working Certificates. But his favorite pastimes have always been swimming in the pool and hanging at the beach with human and canine pals alike. After much debate and consideration, Willie’s human family opted for “benign neglect.” In other words, they decided to observe the enlarged lymph node (and the rest of Willie) very closely and only start treatment when he showed clinical signs. For fourteen months, there appeared to be no change, but then several of Willie’s lymph nodes seemed to get bigger. Additional diagnostics showed that a subset of the tumor cells was trying to grow out, and at that point, Willie started treatment with the chemotherapy protocol that seemed most appropriate for his type of lymphoma. Willie’s primary care veterinarian, his oncologist, and Dr. Modiano
had anticipated that the tumor would grow slowly, but none of them knew
how Willie would respond to treatment once a dominant population of malignant
cells became established. To everyone’s delight, Willie responded
exceptionally well. He is now more than twelve years old, and he has
been on therapy for more than 18 months. Although a step slower due to
age and a touch of arthritis, he still gives the new pups at home a run
for their money, especially in the pool. Recently Willie’s owners
said “We
anticipate that some time in the not too distant future, either the effects
of the medicines or simply his age will affect him, but we are thrilled
that his quality of life has not suffered even one day since this odyssey
began; and when he finally leaves us, we will be comforted by the fact
that he lived so fully to the end.” Well, here’s to many
more years for Willie to enjoy life in the company of friends. Meet NathanNathan is a dignified champion. Like most Rottweilers, he is handsome and rugged, but he is also a loveable companion. Nathan is an American and Canadian Champion, a multiple Best of Breed winner and winner of multiple group placements. He has been an Award of Merit recipient multiple times at Rottweiler Club Specialty Shows. He retired from a show career to participate in agility and herding events. He obtained his AKC Agility Excellent and Agility Excellent Jumpers titles, as well as an AKC Herding Started title (with all three qualifying legs coming with placements!) Nathan also served as a demonstration dog to teach children how to be safe around dogs. For four years, Nathan visited approximately a dozen libraries each summer and presented a program developed by the AKC called “Safety around Dogs.” Nathan’s owner says, “With all of Nathan's accomplishments, accolades and titles, he was and still is my buddy.” Nathan was three qualifying runs away from having an AKC Friends who were not sure amputation was the right choice have seen Nathan since and remarked that amputation was exactly the right thing to do. Nathan is healthy and happy. He certainly does not know anything is different; he walks, he jumps in the car, he jumps on the bed and he hikes his leg in a manner that puts most boy dogs to shame! He still competes with his granddaughter on the weave poles in the back yard. Nathan also had six rounds of carboplatin chemotherapy. There were a few choices, but carboplatin had less side effects. He tolerated the treatment exceptionally well. It is now 18 months since Nathan was diagnosed and started treatment. He is one of those 20-30% of dogs that surpass the odds and survive more than a year. We hope he will be among those that make it three years and beyond from the time of diagnosis. More importantly, though, for Nathan, every day with cancer has simply been another day. He does not know he is sick and he does not consider himself a hero. He is simply a lucky dog that has a family who loves him, and that is just fine by him! Nathan’s picture was taken at a “glamour" studio about
six months after his amputation. Nathan’s “Mom” wanted
to include it to let readers know how much she appreciates him, and how
truly special Nathan is to her. If you have a story about your family’s battle with cancer that you would like to see printed in a future newsletter or posted on our web site, please send it to us in a letter (~500 words). We will try to post new stories as time and space permit. Download a PDF version of this page here. |
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University of Minnesota College of Veterinary Medicine | University of Minnesota Cancer Center • © 2004-2023 Modiano Lab Site Design by © Klein Buendel Inc. Updated April, 2023 |
To
date, we have
recruited more than 100 dogs with lymphoma and
leukemia and more than 60 dogs with bone cancer for
this project. Along with their unaffected relatives and
other control dogs, this project now includes more than
400 participants. We will continue to accrue cases for
this project through the remainder of the year,
especially as samples from dogs enrolled in this project
will be shared with other investigators who have
recently received funding from the AKC Canine Health
Foundation to map heritable factors that influence bone
cancer. We are especially grateful to all the families
that have allowed their dogs to participate, and to all of
our colleagues in the veterinary profession who have so
graciously given their time to help us with our
recruitment efforts.
In
particular, our
group documented recently that a major group of
canine lymphomas, specifically those derived from “B
cells” or the cells that make antibodies, express a
protein called “CD20”. This protein has offered an
exceptional target for treatment of various types of
lymphoma in people. The characterization of the
canine equivalent for this protein offers an opportunity
to develop equivalent reagents (antibodies directed
against the canine CD20) to treat canine B cell
lymphoma.
When
Willie was just over 9 years old (and still actively running in various
agility venues), he developed an enlarged lymph node in his neck that his
veterinarian did not think looked quite right. For the most part, lymphoma
is a relatively straightforward disease to diagnose, but Willie’s
case was different. It took several pathologists, a highly sensitive DNA
test, and extensive discussion among oncology specialists at a national
meeting to come to a consensus that, not only did Willie have lymphoma,
but it originated from “T cells,” a form that often does not
respond very well to treatment. However, this was only the beginning. Willie’s
family then had to consider what was the right thing to do for him. There
were various treatment options, but there seemed to be as many reasons to
treat him as not. For example, Willie did not have severe clinical signs
- in fact, other than the enlarged node in his neck, he showed virtually
no effects from the disease. By itself, this was not unusual, as many dogs
with lymphoma don’t show signs of illness (and by-and-large, these
dogs respond better to treatment). What was more unusual was the fact that
the disease did not seem to have spread to other lymph nodes throughout
his body (as most lymphomas do by the time they are diagnosed); and the
appearance of the cells under the microscope, which had in part made the
diagnosis challenging, suggested that this was a slowly progressing tumor.
On the other hand, cancer is unpredictable, and it turned out that other
members of Willie’s family had been diagnosed in the past with similar
types of lymphoma.
Masters
Agility title (which requires 10 qualifying legs) and would have been the
first Champion Rottweiler in the history of the breed to have an MX title,
when his family noticed that he seemed to be giving a bit less than 100%
in performance events. He was just under 9 years old at the time, and that
was simply not like him. It was then that he was diagnosed with bone cancer.
Unfortunately, Nathan’s human family had dealt with this disease before,
but their experience had been good. To them, there was no question about
pursuing treatment, which included amputating the leg and following up with
chemotherapy. Without this treatment, Nathan would have had a 50% chance
of living an additional 4 months. Other people commented a dog like Nathan,
who was so noble, dignified, active and athletic would lose his dignity
if he had a leg amputated; but Nathan’s family responded by saying
that “a dead dog would have nothing at all.”