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Ross - ET Overview


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University of Maryland Baltimore
Experimental Therapeutics Symposium 2009

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Ross - ET Overview

  1. 1. Program Leader Douglas D. Ross, MD, PhD Clinical Program Leader Martin J. Edelman, MD Experimental Therapeutics Molecular & Structural Biology Hormone Responsive Cancers Viral Oncology (Developing) Tumor Immunology (Developing) X-Ray Crystallography Clinical Research Proteomics Flow Cytometry Experimental Therapeutics Biopolymer Tissue/ Biorepository Translational Biostatistics
  2. 2. Welcome to the 10 th annual ET retreat! <ul><li>Thanks to Bonita Chandler and Kimbrick Knox…and staff! </li></ul><ul><li>Give Kent your presentations before session starts if possible…stay on schedule </li></ul><ul><li>Please fill out the evaluations at the end of retreat – give them to Bonita </li></ul><ul><li>Booklet of presentations pending… </li></ul>
  3. 3. ET Program Aims <ul><li>Identify mechanisms of drug action/resistance , and new targets/pathways for anticancer therapy using innovative basic and clinical research methods. </li></ul><ul><li>Investigate treatment outcome disparities in cancer using innovative basic and clinical research methods. </li></ul><ul><li>Discover and validate novel cancer therapeutics and innovative preclinical models for clinical trials and drug development </li></ul>
  4. 4. Members and Aims Clinical trials Badros, Baer, Bauer, Edelman, Garofalo, Gojo, Kleinberg, Greenwald, Hess, Ross, Zimrin, Tian, Suntha, Sausville, Regine Outcome disparities Baquet, Gordon, Edelman, Carter-Pokras, Tracy, Mullins, McGuire, Davidoff, Holt, Badros, Meiller, Baer AIM 2 Preclinical Models, Novel therapeutics Coop, Sadowska, Bryant, Fang/Tan, Ross, Gerratana, Seley, MacKerell, Edelman, Hosmane, Daniel AIM 3 Drug mechanisms/resistance HR Alexander, Varghese, Baer, Cullen, Fenselau, H. Wang, Nakanishi, Ross, Civin Targets / pathways Aurelian, Bauer, Black, Carey, Farber, Feldman, Yarowsky, J-Y Wang, J-B Wang, Stass, Sausville, Jiang AIM 1
  5. 5. ET Program Statistics 2009 (without TII and VO) <ul><li>Total Membership 56 </li></ul><ul><ul><li>40 Full Members, 16 Associate Members </li></ul></ul><ul><li>19+ Full Members with peer-reviewed funding 50% </li></ul><ul><li>Total annual cancer funding $6.6M </li></ul><ul><ul><li>Peer-reviewed NCI $2.6M </li></ul></ul><ul><ul><li>Peer-reviewed NIH or other $1.9M </li></ul></ul><ul><ul><li>Other cancer funding $2.1M </li></ul></ul><ul><li>Program focused publications 992 </li></ul><ul><li>(past 5 yrs – 8.6 % are Intraprogrammatic) </li></ul>
  6. 6. Aim 1: New targets and pathways and drug resistance <ul><li>Targeting the cell cycle </li></ul><ul><ul><li>UCN-01, other cell cycle active agents (Sausville, Edelman, Gojo) </li></ul></ul><ul><li>Novel heat shock protein </li></ul><ul><ul><li>H11 protein (Aurelian) </li></ul></ul><ul><li>Eicosanoid pathway </li></ul><ul><ul><li>COX-2 (Edelman, Horiba, Fulton) </li></ul></ul><ul><li>Drug sensitivity and resistance </li></ul><ul><ul><li>Control of BCRP expression and clinical drug resistance (Ross) </li></ul></ul><ul><ul><li>Mitochondrial basis for cisplatin activity (Cullen) </li></ul></ul><ul><ul><li>mTOR and resistance in AML (Baer) </li></ul></ul><ul><li>Collaboration with TI program: Immunologic barriers (Strome, Rapoport, Ostrand-Rosenberg) </li></ul>
  7. 7. Aim 2: Epidemiological and Biological Basis for Disparities <ul><li>Genetic polymorphisms in AML (Baer) </li></ul><ul><li>Racial differences in H&N outcomes (Cullen) </li></ul><ul><li>Racial differences in esophageal cancer epidemiology (Mishra, Baquet) </li></ul><ul><li>Different toxicities for bortezomib, zometa in myeloma (Badros) </li></ul>
  8. 8. Aim 3: Novel cancer therapeutics and Preclinical Development <ul><li>Hosmane: fat nucleosides </li></ul><ul><li>MacKerell: cad design/screening </li></ul><ul><li>Fang: SynStat drug interaction software (R01 submitted) </li></ul><ul><li>Sadwoska/Lapidus/Edelman/Ross: preclinical modeling – testing novel agents </li></ul><ul><li>Daniel: nanoparticles for drug delivery </li></ul><ul><li>Gerratana: novel synthetic methods </li></ul><ul><li>Edelman: anti-telomerase therapies </li></ul>
  9. 9. Clinical Trials (partial list) <ul><li>Aim 1: </li></ul><ul><ul><li>mTOR inhibition in AML- GCC 0706 (Baer) </li></ul></ul><ul><ul><li>Radiotherapy to sensitize to chemotherapy (Regine) </li></ul></ul><ul><ul><li>UCN-01/perifosine (Gojo) Phase I/II SNS025 Myeloma: (Badros) </li></ul></ul><ul><ul><li>Phase 2 R-Roscovitine in lung (Edelman) </li></ul></ul><ul><ul><li>Phase 1 AZD7762 / Gemcitabine in solid tumors (Sausville) </li></ul></ul><ul><ul><li>Anticipated SCH727965 Phase I: Heme malignancies (Gojo) </li></ul></ul><ul><ul><li>Planned SCH727965 Phase IIs </li></ul></ul><ul><ul><ul><li>Lung / Breast : Edelman / Tkaczuk </li></ul></ul></ul><ul><ul><ul><li>Melanoma: Sausvillle </li></ul></ul></ul><ul><ul><li>Eicosanoids </li></ul></ul><ul><ul><ul><li>UMGCC 08XX: Apricoxib and MDSCs in NSCLC (Horiba) </li></ul></ul></ul><ul><ul><ul><li>UMGCC 08XX: Randomized phase II trial of chemotherapy + apricoxib in recurrent NSCLC. </li></ul></ul></ul><ul><li>Aim 2: </li></ul><ul><ul><li>Baltimore City Program (Garrett-Ray) </li></ul></ul><ul><ul><li>COX-2 and race in aerodigestive tract malignancies (Horiba) </li></ul></ul><ul><li>Aim 3: </li></ul><ul><ul><li>KML-001/cisplatin phase I (Edelman), R21 </li></ul></ul><ul><ul><li>S100 directed therapy with pentamidine (Sausville), R21 </li></ul></ul>
  10. 10. Multi-Investigator Grants <ul><li>U01 (with Wayne State) </li></ul><ul><ul><li>Gojo – Phase I trial of in AML </li></ul></ul><ul><li>N01 (with U. Chicago) </li></ul><ul><ul><li>Chumsri – </li></ul></ul><ul><ul><li>Edelman – LOI – Topotecan + ABT-737 in SCLC </li></ul></ul><ul><li>P30 (Dorsey) </li></ul><ul><li>SPORE (with TI, Cullen, Suntha) </li></ul><ul><li>Nanotechnology – Swaan et. al. </li></ul>
  11. 11. Progam Meetings <ul><li>Third Tuesday of each month </li></ul><ul><li>4:00 PM-5:00 PM </li></ul><ul><li>9 th Floor Bressler Conference Room (BRB 9-031) </li></ul><ul><li>Please mark your ca </li></ul><ul><li>Calendars! </li></ul>
  12. 12. New Pilot Grant Competition <ul><li>P30 supplement – Funds for pilot grants </li></ul><ul><li>9-1-09 to 8-31-11; $100K from NIH to be matched by $100K from UMGCC </li></ul><ul><li>$40,000 to each program over 2 years </li></ul><ul><ul><li>1 award of $20,000 per year </li></ul></ul><ul><li>Pilot grant applications must utilize one of the UMGCC developing shared services: </li></ul><ul><ul><li>Flow Cytometry </li></ul></ul><ul><ul><li>X-ray Crystallography </li></ul></ul><ul><ul><li>High Throughput Screening </li></ul></ul><ul><ul><li>Pathology Biorepository (Tissue Bank) </li></ul></ul>
  13. 13. Time to Renew P30 – Already!! <ul><li>Timetable for ET: </li></ul><ul><ul><li>April 15, 2010 – first draft due for external review </li></ul></ul><ul><ul><li>June 15, 2010 – revised draft due </li></ul></ul><ul><ul><li>Sept 25, 2010 – final grant to NIH!!! </li></ul></ul><ul><li>How you can help – respond to requests to provide: </li></ul><ul><ul><li>Updated funding information </li></ul></ul><ul><ul><li>Updated collaborative publications – with ET members and other programs </li></ul></ul><ul><ul><li>Descriptions of your research and important recent findings </li></ul></ul><ul><ul><li>Attend program meetings – make your voice heard! </li></ul></ul>
  14. 14. Clinical Leader <ul><li>Dr. Edelman </li></ul>
  15. 16. New Recruitments <ul><li>Li Mao – New co-leader of ET program </li></ul><ul><li>Curt Civin – Stem cell program </li></ul>
  16. 17. P30 Critique – Summary <ul><li>Broad programmatic effort without adequate focus on: </li></ul><ul><ul><ul><li>Target </li></ul></ul></ul><ul><ul><ul><li>Methodological approach </li></ul></ul></ul><ul><ul><ul><li>Preclinical model assessment </li></ul></ul></ul><ul><ul><ul><li>Drug discovery in clinical trials </li></ul></ul></ul><ul><ul><li>Need for increased investigator-initiated clinical trials that derive from the laboratories of the Program </li></ul></ul><ul><ul><li>“… Program leaders [have not] guided the membership towards coordinated approaches that will lead to multi-investigator scientific initiatives and grants” </li></ul></ul><ul><ul><li>“ It is not convincing that the Program will make significant progress in the near future or add considerably to the national effort in discovery and development of important anti-cancer drugs.” </li></ul></ul>