Figure 16.45a The Biology of Cancer (© Garland Science 2007)

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Presentation transcript:

Figure 16.45a The Biology of Cancer (© Garland Science 2007)

Figure 16.21c The Biology of Cancer (© Garland Science 2007)

EGF-R Molecular Evaluation of Biopsy Samples Can Provide Indications of Drug Delivery and Efficacy I

EGF-R pEGF-R ?? Molecular Evaluation of Biopsy Samples Can Provide Indications of Drug Delivery and Efficacy II

Figure The Biology of Cancer (© Garland Science 2007) The Issue of Cancer Stem Cells

Reversal of Tumor Growth by Induction of Redifferentiation Acute Promyelocytic Leukemia reverted to Neutrophils (stem-like) (ATRA) Possible Mechanism: Proteosome-mediated destruction of PML-RAR protein Also note: 13-cis-retinoic acid delays progression of premalignant mouth & throat to frank head-and- neck cancers. Creation by 15:17 translocation

Induction of Apoptosis

Shutting Down Instigating Oncogene Sometimes But Not Always Achieves Permanent Regression of the Tumor Failure

Figure 16.11a The Biology of Cancer (© Garland Science 2007) Blockade of Key Protein – Protein Interactions Case 1: MDM2/P53

A Component of Green Tea Blocks Key Hydrophobic pockets of the Apototic Inhibitory Proteins Bcl-XL & Bcl-2

Blockade of the Apoototic Protein –Binding Site of Bcl-XL Promotes Apoptosis

Figure The Biology of Cancer (© Garland Science 2007) A Family Tree of The 518 Members of the Set of Human Protein Kinases

Figure 16.16a The Biology of Cancer (© Garland Science 2007) An Ingenious Approach to Screenng Candidate Compunds for Kinase Activity

Figure The Biology of Cancer (© Garland Science 2007) The 9:22 Translocation & CML

Figure 16.17a The Biology of Cancer (© Garland Science 2007) Cell-Based Assay of BCR-ABL Inhibitors

Figure 16.10a The Biology of Cancer (© Garland Science 2007) Gleevec – The Poster Child of Rationale Anti-Cancer Drug Design

Figure 16.25b The Biology of Cancer (© Garland Science 2007) Molecular & Cellular Demonstrations of Gleevec’s Efficacy Molecular Cytological

Table 16.2 The Biology of Cancer (© Garland Science 2007)

Figure 16.26c The Biology of Cancer (© Garland Science 2007) Emergence of Resistance to Gleevec

Isolation and Characterization of Gleevec-Resistant BCR-ABL Mutants

Figure 16.31a The Biology of Cancer (© Garland Science 2007) EGF-Receptor Tyrosine Kinase Receptor Inhibitors Iressa & Tarceva

Figure 16.33b The Biology of Cancer (© Garland Science 2007) Resistance to EGF-Receptor Tyrosine Kinase Inhibitors

Figure 16.8 The Biology of Cancer (© Garland Science 2007)

Figure The Biology of Cancer (© Garland Science 2007) Velcade & Multiple Myeloma

Figure The Biology of Cancer (© Garland Science 2007) Velcade Interferes With the NF-Kb Pathway

Figure 16.38b The Biology of Cancer (© Garland Science 2007) EMSA Shows Importance of NF-Kb Signalling in MM and Dramatic Reduction of NF-Kb Levels by Velcade Gel Shift Proof with DN

Figure 16.36b The Biology of Cancer (© Garland Science 2007) Combination Therapy

Figure 16.40a The Biology of Cancer (© Garland Science 2007) The Hedgehogs (Sonic, indian & Desert) are Involved in the Many Cancers esp. Pancreatic Cancer, Gliomas and Basal Cell Carcinoma

Figure 16.40d The Biology of Cancer (© Garland Science 2007) Expression of Patched and Hedgehog – an Autocrine Loop Effect of HH Neutralizing Antibody

Figure 16.42b The Biology of Cancer (© Garland Science 2007) A Inhibitor of Smoothened, HhAntag, Shows Promise in a Mouse Medulloblastoma Model

Rapamycin Inhibits mTOR, a Key Regulator of Growth An immunosuppressive that inhibits tumor formation Shrinkage and reduced angiogenesis in transplanted colon adenocarcinoma Anti-Osteosarcoma effect in humans