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 16.30 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 16.12 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 16.24 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 16.35 The Biology of Cancer (© Garland Science 2007)

Velcade & Multiple Myeloma

Figure 16.37 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