The Use of Antiangiogenic Factors in the Treatment

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The Use of Anti-angiogenic Factors in the Treatment of Oncologic Disease Kyle Treesh, PA-S

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?

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

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

What is angiogenesis? • Think way back to pathophysiology… • Angiogenesis is the formation of blood vessels in a tissue initiated by VEGF and bf. GF • 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

Anti-angiogenesis factors • Protein anti-angiogenic agents • Monoclonal antibody anti-angiogenic agents • Metronomic chemotherapy

Bevacizumab/Avastin • 1 st FDA-approved Angiogenesis Inhibitor • Approved for use with chemotherapy in

Bevacizumab/Avastin • 1 st 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

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

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 therapies? • Over 50 angiogenesis inhibitors in ongoing clinical trials

The bottom line… • Angiogenesis inhibitors have the potential to prolong cancer patients’ quantity

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

For more information: • The American Cancer Society www. cancer. org • The National Cancer Institute www. cancer. gov

Questions?

Questions?

References: 1. Jemal A, Murray T, Ward E, Samuels A, Tiwari R, Ghafoor A,

References: 1. Jemal A, Murray T, Ward E, Samuels A, Tiwari R, Ghafoor A, et al. Cancer Statistics, 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_4 X_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_4 X_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_4 X_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_4 X_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_4 X_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_4 x_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. 14. Siemann DW and Shi W. Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. 2004. International Journal of Radiation Oncology*Biology*Physics 60: 1233 -1240. 15. Klement G, Huang P, Mayer B, Green SK, Man S, Bohlen P, et al. Differences in therapeutic indexes of combination metronomic 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.