A Beginner's Guide to Targeted Cancer Treatments

Standards Information Network (Verlag)
  • 1. Auflage
  • |
  • erschienen am 9. Mai 2018
  • |
  • 360 Seiten
E-Book | ePUB mit Adobe-DRM | Systemvoraussetzungen
978-1-119-12682-9 (ISBN)
Highly Commended in the category of Oncology at the British Medical Association Awards 2019

The accessible guide to the principles behind new, more targeted drug treatments for cancer

Written for anyone who encounters cancer patients, cancer data or cancer terminology, but have no more than a passing knowledge of cell biology. A Beginner's Guide to Targeted Cancer Treatments provides an understanding of how cancer works and the many new treatments available.

Using over 100 original illustrations, this accessible handbook covers the biology and mechanisms behind a huge range of targeted drug treatments, including many new immunotherapies. Dr Vickers translates a complex and often overwhelming topic into something digestible and easily understood. She also explains what cancer is, how it behaves and how our understanding of cancer has changed in recent years.

Each chapter takes the reader through how new cancer drugs work and their benefits and limitations. With the help of this book, readers will be able to better understand more complex, in-depth articles in journals and books and develop their knowledge. This vital resource:

Offers the latest insights into cancer biology
Provides a broad understanding of how targeted cancer treatments work
Describes many of the new immunotherapy approaches to cancer treatment, such as checkpoint inhibitors and CAR-modified T cells
Helps readers feel confident discussing treatment options with colleagues and patients
Provides an overview of which treatments are relevant to each of the most common solid tumours and haematological cancers, and the rationale behind them
Demystifies the jargon - terms such as the EMT, cancer stem cells, monoclonal antibodies, kinase inhibitors, angiogenesis inhibitors etc.
Explains the resistance mechanisms to many new treatments, including issues such as the way cancer cells diversify and evolve and the complex environment in which they live
1. Auflage
  • Englisch
  • USA
John Wiley & Sons Inc
  • Für Beruf und Forschung
  • Reflowable
  • 26,36 MB
978-1-119-12682-9 (9781119126829)

weitere Ausgaben werden ermittelt
DR. ELAINE VICKERS is the Founder of Science Communicated Ltd, an independent company creating courses and educational materials that explain cancer biology and the science behind targeted cancer treatments. In partnership with numerous hospitals, institutes, charities, companies and clinical trials units, her teaching reaches many hundreds of nurses, doctors, pharmacists and clinical trials coordinators each year. Dr. Vickers has a degree in Medical Science from the University of Birmingham and a PhD in Molecular Biology from the University of Manchester. She has been working as a science educator and writer for over fifteen years.
Acknowledgments vii

About the Author ix

How to Use This Book xi

Chapter 1 An Introduction to Cancer Cell Biology and Genetics 1

1.1 Introduction 1

1.2 DNA Damage is the Cause of Every Cancer 2

1.3 The Defining Features (Hallmarks) of Cancer Cells 15

1.4 Genetic Variation among Cancer Cells in a Single Tumor 16

1.5 The Cancer Microenvironment 17

1.6 Cancer Spread/Metastasis 19

1.7 Cancer Stem Cells 23

1.8 Obstacles That Prevent us from Curing Cancer 24

1.9 Final Thoughts 28

Chapter 2 Introducing Targeted Cancer Treatments 33

2.1 Introduction 34

2.2 Monoclonal Antibodies 36

2.3 Kinase Inhibitors 48

2.4 Final Thoughts 60

Chapter 3 Treatments That Block Proteins Involved in Cell Communication 65

3.1 Introduction 65

3.2 Introducing Growth Factor Receptors 67

3.3 Drugs That Target EGFR 75

3.4 Drugs That Target HER2 81

3.5 Drugs That Block Other Growth Factor Receptors 85

3.6 Introduction to Signaling Pathways as a Target for Cancer Therapy 86

3.7 Targeting the MAPK Signaling Pathway 87

3.8 Targeting the PI3K/AKT/mTOR Signaling Pathway 94

3.9 Targeting the JAK-STAT Pathway 100

3.10 Final Thoughts 103

Chapter 4 Drugs That Target: Angiogenesis, Fusion Proteins, PARP, Hedgehog Signaling, and CDKs 111

4.1 Angiogenesis Inhibitors: Introduction 112

4.2 Drugs That Block Fusion Proteins: Bcr-Abl, ALK, RET, and ROS1 122

4.3 PARP Inhibitors 127

4.4 Hedgehog Pathway Inhibitors 134

4.5 Cyclin-Dependent Kinase (CDK) Inhibitors 139

4.6 Final Thoughts 145

Chapter 5 Immunotherapies for Cancer 151

5.1 Introduction 152

5.2 A Bit About Cancer and the Immune System 154

5.3 Checkpoint Inhibitors 160

5.4 Adoptive Cell Transfer 168

5.5 Modified Bi-specific Antibodies 175

5.6 Therapeutic Cancer Vaccines 176

5.7 The Future of Immunotherapy 181

Chapter 6 Targeted Treatments for Common Solid Tumors 187

6.1 Introduction 188

6.2 Targeted Treatments for Breast Cancer 188

6.3 Targeted Treatments for Prostate Cancer 200

6.4 Targeted Treatments for Lung Cancer 204

6.5 Targeted Treatments for Bowel Cancer 214

6.6 Targeted Treatments for Malignant Melanoma Skin Cancer 220

6.7 Targeted Treatments for Kidney Cancer 225

6.8 Targeted Treatments for Head and Neck Cancer 231

6.9 Targeted Treatments for Brain Tumors 235

6.10 Targeted Treatments for Bladder Cancer 236

6.11 Targeted Treatments for Pancreatic Cancer 240

6.12 Final Thoughts 244

Chapter 7 Targeted Treatments for Hematological Cancers 259

7.1 Introduction 259

7.2 A Bit About Hematological Cancers 260

7.3 Antibody-Based Treatments That Target CD Antigens 274

7.4 Drugs That Block B Cell Receptor Signaling 287

7.5 Bcr-Abl Inhibitors 292

7.6 Drugs That Block the Proteasome 294

7.7 Thalidomide and its Derivatives 297

7.8 JAK2 Inhibitors 298

7.9 Bcl-2 Inhibitors 299

7.10 FLT3 and KIT Inhibitors 301

7.11 IDH2 Inhibitors 304

7.12 CAR-Modified T Cell Therapy 304

7.13 Final Thoughts 304

Appendix 313

Glossary of Terms 315

Index 329

An Introduction to Cancer Cell Biology and Genetics


It is impossible to describe targeted cancer treatments without mentioning what it is they target. And when I try to explain what it is they target, I find myself going back to the beginning and explaining where cancers come from, what faults they contain, and why they behave as they do. And in order to explain that, I need explain concepts such as different types of DNA damage, oncogenes and tumor suppressor genes, and the hallmarks of cancer cells.

Hence, in this chapter, I provide an overview of the causes and consequences of DNA mutations in cells. And I describe how even just a handful of key mutations can force a healthy cell to become a cancer cell.

I also describe the cancer microenvironment - the cells and structures that cancer cells live among. Cancer cells have the ability to exploit their microenvironment and in many instances manipulate it. I explain what impact this has when doctors come to treat people with the disease.

In addition, I tackle topics such as genomic instability and intratumoral heterogeneity. Perhaps these are topics that right now don't mean anything to you, and you're unsure of why you need to know about them. But it's only through understanding these concepts that you can appreciate the limitations of targeted (and standard) cancer treatments and the promise of immunotherapy. It is also important to understand why cancer spreads and how cancers evolve and change over time.

Finally, I wrap up the chapter with a brief overview of why cancer is so difficult to treat successfully and why so many people currently cannot be cured.


This book is all about the science behind targeted cancer treatments. And, almost without exception, all targeted cancer treatments work by targeting proteins that are either inside or on the surface of cancer cells or the cells around them. So in order to explain how targeted cancer treatments work, I need to describe the proteins found in cancer cells and how they differ from those in healthy cells. In order to do this, I need to explain the different types of DNA damage that cancer cells contain, because a cell's DNA is its instruction manual telling it how to make proteins. If we know what DNA damage a cell contains, this will tell us what faulty proteins it's making. And if we know what faulty proteins it's making, we will know which targeted treatments might work against it.

A general understanding of the DNA damage that cancer cells contain, and what impact this has on cancer cells, should help you make sense of why some treatments are applicable to some cancer patients and not others. It should also help you understand why it can be helpful to test a patient's cancer cells for the presence or absence of various DNA mutations.

So this chapter is all about cancer cells, DNA, and proteins. And, along with the chapter that follows (which is all about the two main groups of targeted cancer treatments: monoclonal antibodies and kinase inhibitors), this chapter will hopefully provide you with all the background information you need to make sense of the rest of the book.

However, even in this chapter, I've made some assumptions about what you do and don't know. For example, I've assumed that you have a rough idea of what DNA is and how cells use their DNA to make proteins. I'm also assuming that you know what proteins are and a bit about what some of them do. If you're not familiar with these concepts, I would recommend first of all taking a look at the Appendix, which contains a list of reading material about cells, DNA, chromosomes, genes, and proteins. When you've had a look at that, you'll be ready to read further.


Our cells' DNA is essentially a huge instruction manual telling our cells what proteins to make, how to make them, when to make them, what to do with them, and when to destroy them. In turn, the proteins our cells make dictate their behavior. For this reason, if you damage a cell's DNA, you also end up with damaged proteins, leading to abnormal behavior.

A cancer starts to develop when a single cell accumulates DNA damage that causes it to make various faulty proteins that force it to behave abnormally. This normally doesn't happen. A cell that finds its DNA is damaged usually either tries to repair the damage, or it self-destructs through a process called apoptosis.1 But, if a cell doesn't notice the damage and survives and later accumulates more damage, it might ultimately become a cancer cell.

Over the past 40 years or so, scientists have been gradually discovering what DNA damage cancer cells contain and how this affects their proteins. The scientists' primary focus has been to study the DNA that contains the instructions to make proteins - our cells' genes. This protein-coding DNA only takes up about 1% or so of our cells' total DNA [1]. (What exactly the other 99% of our cells' DNA is for is a matter of continued debate among scientists.)

Through initiatives such as The Cancer Genome Atlas [2] and the International Cancer Genome Consortium [3], hundreds of scientists have amassed an incredible catalog of information about the thousands of different DNA mutations cancer cells contain [4]. They've also discovered that different types of cancer differ from one another in terms of the mutations they contain and the treatments they respond to. And as well as the differences, we know that important similarities can exist between cancers that arise in different organs. For example, some breast cancer patients may have tumors that overproduce2 a protein called HER2, as do the tumors of some patients with stomach cancer [5].

Box 1.1 The names of genes and their proteins

As you read this book you might notice that protein names are written normally but that gene names are written in italics. For example, the HER2 gene contains the instructions for making HER2 protein. You might also notice that sometimes the gene and protein have different names. An example of this is the TP53 gene, which contains the instructions for making a protein called p53. It's also possible for a gene to contain the instructions for making more than one protein. For instance, the CDKN2A gene (sometimes referred to as the CDKN2A locus) contains the instructions for making several proteins, two of which are called p16INK4a and p14ARF.

To add to the confusion, some genes and proteins have more than one name. For example, the HER2 gene is also called ErbB2 and NEU. The reasons behind the various names often have a lot to do with what organism or group of cells the gene/protein was discovered in; if it's similar to another gene/protein that has already been discovered; what role the gene/protein is thought to play in the cells or organism it was found in; and whether or not abnormalities in the gene/protein cause disease. For example, HER2 stands for human epidermal growth factor receptor-2, because it's similar in structure to HER1 (although we usually refer to HER1 as the EGF-Receptor). HER2 is also called ErbB2 because a very similar gene, called Erb-b, was discovered in a disease-causing virus called the avian erythroblastosis virus. And HER2 is also called NEU because a faulty version of it can cause a cancer called neuroblastoma in rodents.

A final point to note is that gene names are often written in capital letters, whereas protein names aren't. But this convention isn't always adhered to.

Because there is lots to say about the DNA mutations in cancer cells, I'm going to split it up into different topics. First, I'll talk about what causes the DNA mutations found in cancer cells (Section 1.2.1). Then I'll describe what types of mutation occur (see Section 1.2.2), how the number of mutations in cancer cells varies (see Section 1.2.3), and which mutations have the greatest effect on cell behavior (see Section 1.2.4). Then I'll talk about some of the most common gene mutations in cancer cells and what impact they have (Section 1.2.5).

Later in the chapter, we will look at the defining characteristics of cancer cells (Section 1.3), how cancer cells in a tumor can be genetically different from one another (Section 1.4); how they interact with and influence the non-cancer cells that live alongside them (Section 1.5), and how they invade and spread (Section 1.6).

All of this information is gradually helping scientists create new, more targeted cancer treatments, which are the subject of the rest of this book.

1.2.1 Causes of DNA Mutations

There are many different reasons why our cells' DNA gets damaged. Some of this damage is natural and unavoidable, whereas some of it is down to our lifestyle, behaviors, exposures, geographical location, and even...

Dateiformat: ePUB
Kopierschutz: Adobe-DRM (Digital Rights Management)


Computer (Windows; MacOS X; Linux): Installieren Sie bereits vor dem Download die kostenlose Software Adobe Digital Editions (siehe E-Book Hilfe).

Tablet/Smartphone (Android; iOS): Installieren Sie bereits vor dem Download die kostenlose App Adobe Digital Editions (siehe E-Book Hilfe).

E-Book-Reader: Bookeen, Kobo, Pocketbook, Sony, Tolino u.v.a.m. (nicht Kindle)

Das Dateiformat ePUB ist sehr gut für Romane und Sachbücher geeignet - also für "fließenden" Text ohne komplexes Layout. Bei E-Readern oder Smartphones passt sich der Zeilen- und Seitenumbruch automatisch den kleinen Displays an. Mit Adobe-DRM wird hier ein "harter" Kopierschutz verwendet. Wenn die notwendigen Voraussetzungen nicht vorliegen, können Sie das E-Book leider nicht öffnen. Daher müssen Sie bereits vor dem Download Ihre Lese-Hardware vorbereiten.

Bitte beachten Sie bei der Verwendung der Lese-Software Adobe Digital Editions: wir empfehlen Ihnen unbedingt nach Installation der Lese-Software diese mit Ihrer persönlichen Adobe-ID zu autorisieren!

Weitere Informationen finden Sie in unserer E-Book Hilfe.

Download (sofort verfügbar)

40,99 €
inkl. 7% MwSt.
Download / Einzel-Lizenz
ePUB mit Adobe-DRM
siehe Systemvoraussetzungen
E-Book bestellen