Cancer Drug Discovery Fascinating Anecdotes of Oncology Medicine

History is an erudite teacher, from which we can learn invaluable lessons, both positive and negative. This is especially true for drug discovery and development. While creativity demands we think outside of the box, past successes and failures in creating medicines are gifts that keep on giving. Creation of human medicines involves so many scientific and medical disciplines and history is our indispensable resource of institutional knowledge. This volume in a new series sheds light on successes to emulate and pitfalls to avoid in oncology drug discovery. The series editor blends education with engaging content for aspiring drug developers and helps to foster a deeper understanding.

Key Features

• It aims to integrate biology, chemistry, medicine, and history, which mirrors the multidisciplinary nature of drug development.
• By targeting the next generation drug developers and making efforts to include narrative and historical elements, it differentiates itself from pure technical texts.
• Using history to contextualize drug discovery helps readers to understand why certain strategies worked or failed.
• The inclusion of chemical structures in Chapter 8 makes the book more substantial for scientists with a chemistry background.
• The focus on novel approaches enhances the relevance of the book for the future.

Chapter 1       The Origins of Cancer

1.1       The Carcinogen Theory

            1.1.1    Percival Pott and Scrotal Cancer

            1.1.2    Katsusaburo Yamagiwa and Bunny Ears

            1.1.3 Bruce Ames and Mutagens

1.2        The Worm Theory

1.3       Cancer-Causing Viruses

1.4       Oncogenes

            1.4.1    Gregor Mendel’s Peas

            1.4.2    Thomas Morgan’s Fruit Flies

            1.4.3    Oswald Avery’s DNA

            1.4.4    Rosalind Franklin and Watson‒Crick’s Double Helix

            1.4.5    Michael Bishop and Harold Varmus’s Proto-Oncogenes

             1.4.6    Robert Weinberg’s Ras Oncogene

1.5       Tumor Suppressor Genes

            1.5.1    Henry Harris’s Cell Fusion

            1.5.2.   Alfred Knudsen’s “Two-Hit” Hypothesis

            1.5.3.   Dryja and Friend’s Cloning of the RB Gene

            1.5.4    The True Face of TP53

1.6       Tumor Biomarkers

            1.6.1    History of Tumor Biomarkers

            1.6.2    Advances in Tumor Biomarkers

            1.6.3    The Future of Biomarkers

17.       Summary

Chapter 2       Chemotherapies: Pyrrhic Victory

2.1       Old Is Gold: DNA-Targeting Anticancer Drugs

            2.1.1    Nitrogen Mustards, Beginning of An Era

            2.1.2    Temozolomide: A Blockbuster Chemotherapeutic

            2.1.3    A Drug from a Sea Squirt in the Caribbean

            2.1.4    A Noble Metal for a Noble Cause: Platinum Cancer Drugs

            2.1.5    Epigenetic Cancer Drugs

2.2       Natural Products as Cancer Chemotherapeutics

            2.2.1    Mitomycin C from Japan

             2.2.2    Bleomycin from Japan

             2.2.3    Doxorubicin from Italy

2.3       Microtubule Inhibitors

             2.3.1    Vinca Alkaloids

             2.3.2    Eribulin, the Most Complex Man-Made Drug

             2.3.3    Taxanes 

             2.3.4.   Epothilones

2.4       Antimetabolites

            2.4.1    Methotrexate and Antifolates

            2.4.2    From Bad to Good: 5-FU to Capecitabine

            2.4.3    6-Mercaptopurine (6-MP), a Biphasic Medicine

2.5       Anti-Hormone Cancer Drugs

            2.5.1    Charles Higgins: So Much Owed by So Many to So Few

            2.5.2    Prostate Cancer Drugs

            2.5.3.   Breast Cancer Drugs

2.6       Summary

Chapter 3       Targeted Cancer Therapy: Protein Kinase Inhibitors

3.1       Protein Kinases

            3.1.1    Protein Kinases and Their Discovery

            3.3.2    Classes of Protein Kinases

            3.3.3    Functions of Protein Kinases

3.4       Gleevec Changed the Paradigm

            3.4.1    Chronic Myeloid Leukemia (CML)

            3.4.2    The Philadelphia Chromosome

            3.4.3    Discovery of Gleevec

            3.4.4    Development of Gleevec

            3.4.4    Beyond Gleevec

3.5       Bruton’s Tyrosine Kinase Inhibitors

            3.5.1    Discovery of Ibrutinib (Imbruvica)

            3.5.2.   Development of Ibrutinib (Imbruvica)

            3.5.3.   Acerta and Second-Generation BTK Inhibitors

3.5.4    Third-Generation BTK Inhibitors

3.6       MEK Inhibitors

            3.6.1    Parke-Davis Paved the Way

            3.6.2    MEK Inhibitors on the Market

            3.6.3    Renaissance of the Old Drug from Parke-Davis

3.7       Kinase Inhibitors Today

Chapter 4       Biologic Cancer Drugs

4.1       Introduction

           4.1.1    Antibodies

           4.1.2    Monoclonal Antibodies

4.2       Her-2 and Trastuzumab, Monoclonal Antibodies Came of Age

            4.2.1    Rita Levi-Montalcini and Stanley Cohen

            4.2.2    Axel Ullrich and Dennis Slamon

            4.2.3    From 4D5 to Trastuzumab

            4.2.4    From Trastuzumab to Herceptin

            4.2.5    Beyond Herceptin

4.3       Mendelsohn and Erbitux

            4.3.1    The Murine Monoclonal Antibody

            4.3.2    Humanized Monoclonal Antibody

            4.3.3    The Fate of Sam Waksal

            4.3.4    The Fate of Erbitux

            4.3.5    Small Molecule EGFR Inhibitors

4.4       Monoclonal Antibody Cancer Drugs Today

4.5       Antibody-Drug Conjugates (ADCs)

            4.5.1    Mylotarg, the First ADC

            4.5.2    Resurgence of ADCs

            4.5.3    The China Factor

4.6       Cancer Vaccines: The Holy Grail

            4.6.1    Vaccines for Cervical Cancer

            4.6.2    Vaccines for Liver Cancers

            4.6.3    More Cancer Vaccines in the Market

            4.6.4    Cancer Vaccines Today

4.7       Oncolytic Viruses

Chapter 5       New Modalities of Cancer Treatments

5.1       Molecular Glue Degraders

            5.1.1    Schreiber and Liu at Harvard

            5.1.2    Ubiquitin: A Nobel Protein

            5.1.3    Old Drugs, New Glues

5.2       PROTACs

5.3       Immunotherapy for Cancer

            5.3.1.   William Coley and St. Anthony’s Fire

            5.3.2.   Prelude to Immuno-Oncology (IO)

            5.3.3.   James Alison and Immune Checkpoint Inhibitors

            5.3.4.   Honjo and Programmed Cell Death-1 (PD-1)

5.4       Cell and Gene Therapy

5.4.1    Cell Therapy: CAR T

5.4.2    Gene Therapy

Chapter 6       Artificial Intelligence in Cancer Medicine

6.1       AI in Cancer Diagnosis

6.2       AI in Cancer Drug Discovery

            6.2.1    Target Identification and Validation

            6.2.2    Drug–Target Interaction Prediction

            6.2.3    Personalized Medicine

            6.2.4    Drug Repurposing

            6.2.5    Drug Safety Evaluation

6.3.      AI in Cancer Drug Development

6.4       Summary

Chapter 7       Reflections

7.1       Hallmarks of Cancer

7.2       Cancer Chemotherapies

7.3.      Kinase Inhibitors

7.4       Biologic Cancer Drugs

Chapter 8       Chemical Structures of Key Cancer Drugs

Index