Download Kyle Treesh - University of Kentucky

The Use of Anti-angiogenic
Factors in the Treatment of
Oncologic Disease
Kyle Treesh, PA-S
Bob Hadley, Ph.D., PA-C, Advisor
University of Kentucky
Learning Objectives
• Why do we need new cancer treatments?
• What is angiogenesis?
• What are the anti-angiogenesis agents?
• What agents are FDA-approved?
• What combinations of treatment are best?
• What does the future hold for these
therapies?
U.S. Cancer Statistics
• Cancer is a major public health problem!
• One in four deaths is due to cancer
(570,280 deaths in 2005)
• 1,372,910 new cancer cases in 2005
• Lung and bronchus, and colon and rectum
equal 25% of total cancer deaths
• Breast and Prostate cancers are prevalent
in their respective sexes
What is angiogenesis?
• Think way back to pathophysiology…
• Angiogenesis is the formation of blood vessels in a tissue initiated
by VEGF and bfGF
• Angiogenesis aids in the healing of wounds, proliferates the
endometrium, and is a vital part of pregnancy
• Tumors can also cause angiogenesis to occur in order to bring
oxygen and nutrients to the tumor for growth
• These new blood vessels are the vehicle for metastasis
Anti-angiogenesis factors
• Protein anti-angiogenic agents
• Monoclonal antibody anti-angiogenic
agents
• Metronomic chemotherapy
Bevacizumab/Avastin
• 1st FDA-approved Angiogenesis Inhibitor
• Approved for use with chemotherapy in
the treatment of colorectal cancer
• Prolonged lives 5 months compared to
standard treatment
• No additional side effects!
• Not expected to be a cure, but provides
hope for a longer life
Combination Therapies with Antiangiogenesis agents:
• With Chemotherapy
• With Radiation
• With other anti-angiogenesis agents
• With Vascular Disrupting Agents
• Metronomic Chemotherapy
• Trimodal Therapy
Into the Future…
• What are the limitations of these therapies?
• Can these agents work in all cancer sites?
• Could these agents be used for prevention of a recurrent
cancer (e.g. Breast CA)?
• Will clinicians use these therapies?
• Over 50 angiogenesis inhibitors in ongoing clinical trials
The bottom line…
• Angiogenesis inhibitors have the
potential to prolong cancer
patients’ quantity of life without
diminishing their quality of life
For more information:
• The American Cancer Society
www.cancer.org
• The National Cancer Institute
www.cancer.gov
Questions?
References:
1. Jemal A, Murray T, Ward E, Samuels A, Tiwari R, Ghafoor A, et al. Cancer Statistics, 2005. 2005; CA: A Cancer Journal for Clinicians 55:
10-30.
2. Wittekind C, and Neid N. Cancer Invasion and Metastasis. 2005; Oncology 69: 14-16.
3. ACS, What is antiangiogenesis therapy? 2 April 2005, available at:
http://www.cancer.org/docroot/ETO/content/ETO_1_4X_What_Is_Antiangiogenesis_Therapy.asp?sitearea=ETO. Accessed 3 Nov 2005.
4. Isayeva T, Kumar S, and Ponnazhagan S. Anti-angiogenic gene therapy for cancer (review). 2004: International Journal of Oncology 25:
335-343.
5. ACS, Why do tumors need their own blood supply? 2 April 2005, available at:
http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Why_Do_Tumors_Need_Their_Own_Blood_Supply.asp?sitearea=ETO. Accessed 3
Nov 2005.
6. ACS, How different antiangiogenesis drugs work. 2 April 2005, available at:
http://www.cancer.org/docroot/ETO/content/ETO_1_4X_The_Details_How_Antiangiogenesis_Drugs_Work.asp?sitearea=ETO. Accessed 3 Nov
2005.
7. NCI, Understanding cancer series: angiogenesis. 28 Jan 2005, available at:
http://www.cancer.gov/cancertopics/understandingcancer/angiogenesis. Accessed 3 Nov 2005.
8. ACS, Possible pros and cons of antiangiogenesis drugs. 2 April 2005, available at:
http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Advantages_of_Antiangiogenesis_Drugs.asp?sitearea=ETO. Accessed 3 Nov 2005.
9. Ma L, Giulio F, Viloria-Petit A, Hicklin DJ, du Manior J, Rak J, et al. In vitro procoagulant activity induced in endotelial calls by
chemotherapy and antiangiogenic drug combinations: modulation by lower-dose chemotherapy. 2005; Cancer Research 65: 5365-5373.
10. Hurwitz H, and Kabbinavar F. Bevacizumab combined with standard fluoropyrimidine-based chemotherapy regimens to treat colorectal
cancer. 2005; Oncology 69: 17-24.
11. ACS, Recent research in antiangiogenesis therapy. 2 April 2005, available at:
http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Recent_and_Current_Research_in_Antiangiogenesis_Therapy.asp?sitearea=ETO.
Accessed 3 Nov 2005.
12. ACS, The future of antiangiogenesis. 2 April 2005, available at:
http://www.cancer.org/docroot/ETO/content/ETO_1_4x_The_Future_of_Antiangiogenesis.asp?sitearea=ETO. Accessed 3 Nov 2005.
13. Huber PE, Bischof M, Jenne J, Heiland S, Peschke P, Saffrich R, et al. Trimodal cancer treatment: beneficial effects of combined
antiangiogenesis, radiation, and chemotherapy. 2005; Cancer Research 65: 3645-3655.
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chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. 2002; Clinical Cancer Research 8: 221232.
16. NCI, Angiogenesis inhibitors in the treatment of cancer. 20 May 2002, available at:
http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors. Accessed 3 Nov 2005.