"Angiogenesis and Metastasis" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 3; Number 27; August 2, 2002. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! ANNOUNCEMENTS Did you know that Doxycycline has properties that inhibit a cellular enzyme responsible for new blood vessel formation and cancer metastasis? Check our web site regularly for additional information and updates. Subscribe to our weekly email newsletter online! Call any of our 3 Oncologists (Hahn, King, Carreras), 2 Oncology Residents (Freeman, Turner) or our Oncology Nurses Monday-Friday or email Dr. Hahn for more information and patient consultations. ============================================ THIS WEEK'S TUMOR TIDBIT: ANGIOGENESIS AND METASTASIS ============================================ SUSTAINED ANGIOGENESIS Angiogenesis describes the generation or recruitment of new blood vessels. In normal organs angiogenesis is tightly regulated and in most tissues is not necessary. It appears that new blood vessel development is essential for tumors to grow beyond a size of 1 mm and essential to the process of metastasis. In order to be successful at angiogenesis, tumors must enter complex interactions with their local microenvironment and shift the balance of angiogenesis control towards new blood vessel formation. Clinical implication: If new blood vessel formation or recruitment can be inhibited a tumor should not be able to progress beyond this 1 mm size and should not metastasize. Such therapies may lack normal tissue toxicity since most adult tissues do not require new blood vessel formation. Several human and veterinary clinical trials are currently underway to evaluate the activity of antiangiogenic agents. Preliminary experience with thalidomide as an anti-angiogenic treatment for dogs with measurable disease has been disappointing. The Animal Cancer Institute recently reported significant antitumor responses against measurable tumors using antiangiogenic thrombospondin-I peptides in dogs with lymphoma, head and neck carcinomas, and sarcomas. Current studies are underway to evaluate these peptides in combination with chemotherapy in dogs with lymphoma. TISSUE INVASION AND METASTASIS The process of cancer invasion within tissues and across tissue boundaries (basement membranes) is essential for cancer progression. The process of metastasis requires a number of distinct sub-processes that include invasion, adherence, extravasation, evasion of immune attack, arrest, and angiogenesis. A cancer cell must acquire the ability to perform each sub-process before successful metastases can be seen. Clinical implication: The recent understanding of the determinants for invasion by cancer cells has lead to the development of a number of agents that inhibit cancer invasion. Matrix metalloproteinases (MMPs) have been identified as critical enzymes that facilitate tumor invasion. Several classes of MMP inhibitors are currently under investigation in pre-clinical models and in veterinary cancer patients. No data on the effectiveness of these agents in veterinary patients has been published. Novel metastasis genes and pathways are being examined as potential therapeutic targets. Progress that has been made in our understanding of the basic biology of cancer has uncovered several opportunities for the treatment of cancer. The improved knowledge of cancer biology has allowed differences between cancer cells and normal cells to be identified and has uncovered important interactions that occur between cancer cells the host. In the very near future we can expect novel therapeutic options for cancer to be combined with conventional cancer treatments in the management of human and our veterinary cancer patients. WHAT DO WE DO FOR OUR PATIENTS AT GULF COAST? As part of the cancer care process, we recommend the combination of various agents in an attempt to inhibit blood vessel formation and cancer cell metastasis. Although verified in laboratory studies and not in well- controlled clinical trials, we believe our 'recipe' provides significant control in the growth and spread of cancer in patients with 'high grade' cancers with minimal risk to quality of life. We use a combination of Doxycycline (an antibiotic that inhibits collagenase - an enzyme that allows cells to 'eat' through tissue barriers thus allowing blood vessel cells and cancer cells to migrate to other locations), Piroxicam (a non-steroidal anti- inflammatory drug that inhibits cyclooxygenase - an enzyme overproduced by various cancer cells that allows the formation of a prostaglandin(s) that inhibit the function of the immune system against the cancer), and Cytoxan (a chemotherapy agent that at low and regular dosages inhibits the reproductive capacity of cancer cells and has possible antiangiogenic properties). SUGGESTED READING * The Hallmarks of Cancer and Their Clinical Implications. By Khanna C. Proceedings of the American College of Veterinary Internal Medicine, 2002 (www.acvim.org). * Veterinary Oncology, From "The Practical Veterinarian Series". By Hahn KA. Butterworth-Heinemann Press, 2002. ============================================ I hope this info helps and don't hesitate to call or email us at Gulf Coast Veterinary Oncology! Kevin Kevin A. Hahn, DVM, PhD Diplomate American College of Veterinary Internal Medicine (Oncology) & Overall Nice Guy Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: www.gcvs.com Email: drhahn@gcvs.com