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The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma Introduction George D. Demetri, MD Dana-Farber Cancer Institute Harvard Medical.

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Presentation on theme: "The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma Introduction George D. Demetri, MD Dana-Farber Cancer Institute Harvard Medical."— Presentation transcript:

1 The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma Introduction George D. Demetri, MD Dana-Farber Cancer Institute Harvard Medical School Ludwig Institute for Cancer Research

2 Developmental Therapeutics in Sarcomas Sarcomas are now recognized as important models for rational drug discovery and accelerated clinical developmentSarcomas are now recognized as important models for rational drug discovery and accelerated clinical development Our field needs to expand this beyond targeted therapies for GISTOur field needs to expand this beyond targeted therapies for GIST

3 Developmental Therapeutics in Sarcomas Today’s Topic: Expanding the preclinical and clinical collaborations to accelerate discovery and application in sarcoma researchToday’s Topic: Expanding the preclinical and clinical collaborations to accelerate discovery and application in sarcoma research –Peter Houghton, PhD: cancer modeling –Rich Gorlick, MD: osteosarcoma frontiers –Antony Tolcher, MD: phase I to sarcomas –Chand Khanna, PhD, DVM: sarcoma research is going to the dogs

4 The Question What is the next great target for a specific subtype of sarcoma?

5 Which are the BEST Molecular Targets in Sarcomas? Receptor Tyrosine Kinase RAS-GDP RAF-1 SHC BAD SOS GRB-2 14-3-3 Nucleus BCLX LMitochondria SRC P STAT1+3 P RAS-GTP SAPK P AKT 14-3-3 BAD P RAS-GAP DOK ? MYC PI3K MEK1/2 P P P P P MAPK mTOR P P

6 Which are the BEST Molecular Targets in Sarcomas? Receptor Tyrosine Kinase RAS-GDP RAF-1 SHC BAD SOS GRB-2 14-3-3 Nucleus BCLX LMitochondria SRC P STAT1+3 P RAS-GTP SAPK P AKT 14-3-3 BAD P RAS-GAP DOK ? MYC PI3K MEK1/2 P P P P P MAPK mTOR P Sutent (Pfizer) P Gleevec (Novartis)

7 Molecular Targets in SARCOMAS Receptor Tyrosine Kinase RAS-GDP RAF-1 SHC BAD SOS GRB-2 14-3-3 Nucleus BCLX LMitochondria SRC P STAT1+3 P RAS-GTP SAPK P AKT 14-3-3 BAD P RAS-GAP DOK ? MYC PI3K MEK1/2 P P P P P MAPK mTOR P Sutent (Pfizer) P Zarnestra (JNJ) P PI3kI (PIRAMED) P RAD001 (Novartis) CCI779 (Wyeth) AP23573 (ARIAD) P SORAFENIB (Bayer) Imatinib (Novartis) P BMS354825 (Bristol-MS)

8 Molecular Targets in SARCOMAS Receptor Tyrosine Kinase RAS-GDP RAF-1 SHC BAD SOS GRB-2 14-3-3 Nucleus BCLX LMitochondria SRC P STAT1+3 P RAS-GTP SAPK P AKT 14-3-3 BAD P RAS-GAP DOK ? MYC PI3K MEK1/2 P P P P P MAPK mTOR P Sutent (Pfizer) P Zarnestra (JNJ) P PI3kI (PIRAMED) P RAD001 (Novartis) CCI779 (Wyeth) AP23573 (ARIAD) P SORAFENIB (Bayer) Imatinib (Novartis) P BMS354825 (Bristol-MS) DRUG X DRUG Y DRUG Z DRUG BDRUG C DRUG D

9 Molecular Targets in SARCOMAS Receptor Tyrosine Kinase RAS-GDP RAF-1 SHC BAD SOS GRB-2 14-3-3 Nucleus BCLX LMitochondria SRC P STAT1+3 P RAS-GTP SAPK P AKT 14-3-3 BAD P RAS-GAP DOK ? MYC PI3K MEK1/2 P P P P P MAPK mTOR P Sutent (Pfizer) P Zarnestra (JNJ) P PI3kI (PIRAMED) P RAD001 (Novartis) CCI779 (Wyeth) AP23573 (ARIAD) P SORAFENIB (Bayer) Imatinib (Novartis) P BMS354825 (Bristol-MS) DRUG X DRUG Y DRUG Z DRUG BDRUG C DRUG D DRUG X DRUG Z N DRUG Z X DRUG Z y DRUG Z N DRUG Z A DRUG Z N DRUG Z Z DRUG Z N

10 SARC CTOS Building Effective Collaborations with SARC and others to Answer These Important Questions International Sarcoma Research Groups US Govt ResearchMechanisms Sarcoma Intergroups Individual Investigators Patient Advocacy Groups

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