The Great DiseasesA collaborative approach to real world science in the classroom

Revati Masilamani, Ravi Subramanian and Karina Meiri

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Infectious Disease Neurological Disorders Metabolic Disease Cancer

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CancerStudent Workbook

Unit 1: What is cancer and why should we care? 4Lesson 1.1 5Lesson 1.2 12Lesson 1.3 19Lesson 1.4 27Lesson 1.5 35

Unit 2: What does it mean to be a 'normal' cell? 42Lesson 2.1 43Lesson 2.2 50Lesson 2.3 57Lesson 2.4 65Lesson 2.5 72

Unit 3: How do normal cells become cancerous? 79Lesson 3.1 80Lesson 3.2 88Lesson 3.3 95Lesson 3.4 101Lesson 3.5 107

Unit 4: How does cancer make us sick? 114Lesson 4.1 115Lesson 4.2 122Lesson 4.3 129Lesson 4.4 136

Unit 5 : How do we treat cancer? 143Lesson 5.1 144Lesson 5.2 153Lesson 5.3 160Lesson 5.4 168Lesson 5.5 175Lesson 5.6 182

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Throughout this module, you’ll have not only class lessons, but also this workbook to guide you through your exploration of Cancer. This workbook is designed to provide you with readings to complement your class lessons. We have helped make your reading of this workbook interactive by encouraging you to take notes and answer questions throughout.

This module focuses on understanding cancer as a disease and the challenges of diagnosing and treating it. The Cancer Module has five units, each of which builds upon the others that came before it. The goal of each unit is to answer a new question about cancer, and what this means for our health.

• Unit 1: What is cancer and why should we care?• Unit 2: What does it mean to be a normal cell?• Unit 3: How do normal cells become cancerous?• Unit 4: How does cancer make us sick?• Unit 5: How do we treat cancer?

In Unit 1, we’ll begin our discussion by investigating how our understand-ing of what cancer is has changed over time, and what we currently understand about the role of random mutation in causing cancer. From there, in Unit 2, we’ll focus on how normal cells behave in their tissue communities, and in particular their vulnerabilities to mutation. Then, in Unit 3, we’ll zoom in on how cell function is disrupted in cancer. Next, in Unit 4, we’ll take a broader approach and examine cancer as a disease and the challenges of diagnosis. Finally, in Unit 5, we'll look at how we diagnose and treat cancer and the challenges and opportunities for designing better screens and treatments in the future.

Welcome to theCancer Module!

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Unit 1:Where are we heading?Unit 1: What is cancer and why should we care?

Unit 2: What does it mean to be a 'normal' cell?

Unit 3: How does a normal cell become cancerous?

Unit 4: How does cancer make us sick?

Unit 5: How is cancer diagnosed and treated?

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Unit 1 focuses on what we currently understand about cancer and how our perception of cancer has changed over time.

Lesson 1.1 engages you with the idea that cancer is relevant to you, and is not simply a disease of old age. Lesson 1.2 explores how the historical context has always influenced how cancer has been understood and will investigate the technological breakthroughs that have led to our current understanding of cancer biology. Lesson 1.3 investigates how the three main theories of how cancer is caused were reconciled when we finally understood that cancer is a disease of DNA damage. Lesson 1.4 grapples with the challenges of estab-lishing causation rather than correlation when dealing with diseases of unknown and complex origins such as cancer. Lesson 1.5 will explore how to assess the risk of developing cancer in order to make informed choices about how to minimize that risk.

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W o r k b o o kLesson 1.1

DEFINITIONS OF TERMS

Mortality rate – The rate at which people die from a specific

cancer.

For a complete list of defined terms, see the Glossary.

Notes: ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Why should I care about cancer?

About 8.2 million people die of cancer each year, making cancer the leading cause of death worldwide, and the second leading cause of death in the United States (behind heart disease).

Many people believe that cancer is a disease of elderly people, and it is - if we confine our discussion to clinical symptoms, which most typically appear at around 60 years of age. Even so, about 72,000 cases of cancer are diagnosed in adolescents and young adults each year. Unfortunately while mortality rates (frequency that people die from a particular cancer) have declined in older patients, they remain largely unchanged in the 15-39 age group.

This is largely due to misdiagnosis: young adults are simply not expected to develop cancer, so symptoms may be left untreated for longer periods than in the elderly. As we will see, early identification of cancer is the key to survival.

LESSON 1.1 WORKBOOKWhy should we care about cancer?

The first lesson focuses on two key issues you will encounter as you move through the module: First, cancer is not solely a disease of old age: Although cancers usually reveal clinical symptoms in older patients, they may have originated when that patient was quite young. Second, a tumor that has originated in a young person and spread from its primary location soon after it develops will cause significant mortality if it escapes detection and evolves to resist treatment. For effective preven-tion we need to identify which tumors will evolve to spread before they actually do so, as we shall see in this lesson about Steve Jobs.

LESSON READINGS

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W o r k b o o kLesson 1.1

DEFINITIONS OF TERMS

Carcinogen – An agent able to cause cancer.

MC Questions:

1. Which of the following is NOT a reason high-schoolers should care about cancer?

.a Cancer is often misdiagnosed for people age 15-39;

.b Cancer is the leading cause of death in the US;

.c Cancer mortality rates have not decreased for young adults; or

.d Choices made in high school can affect the risk of developing cancer later.

2. Which of the following might increase your risk of developing cancer?

.a Heavy metals.

.b Smoking.

.c Excessive tanning.

.d All of the above.

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A further issue that has only recently become apparent is that there may be a significant delay between when a cancer develops and when symptoms appear. During this time, as we will see, the cancer is evolving so that it can resist the treatments we currently have available. It follows then that it is critical to minimize the risks of cancer developing in the first place, and this means becoming aware of what these risks are. Some are undoubtedly genetic and thus beyond our control, but others, such as exposure to cancer-causing agents – carcinogens - are often avoidable. Thus, you may have choices now that will profoundly impact your health in the future. As we will, see minimizing cancer risks means being aware of what those choices are.

We don’t have to look far for examples: Celebrities, who are under constant media scrutiny, provide numerous instances of choices made that turn out to have unfortunate consequences. Sometimes are inadvertent: Steve Jobs was diagnosed with pancreatic cancer in 2003, and died 8 years later at only 56, a relatively young age. As we all know, Jobs spent his teens and twenties developing computer hardware, in the process exposing himself to heavy metals such as cadmium and lead, which are now, but were not at the time, appreciated to be carcinogens. Did this exposure increase his chances of developing cancer?

Another example seems more clear-cut. Patrick Swayze also died of pancreatic cancer at a young age - 57. Swayze regularly smoked more than 60-80 cigarettes a day, expos-ing himself to tar compounds that have been well-known carcinogens for over 70 years. While cigarette smoking is linked primarily to lung cancer, it also leads to increased risk of cancer in the throat, colon, breast, and other organs, such as the pancreas. As a nicotine addict, could Swayze have chosen to stop smoking?

Figure 1: Steve Jobs died of pancreatic cancer at the age of 56. Building computers with heavy metals increased his exposure to cancer-causing materials.

Figure 2: Patrick Swayze also died of pancreatic cancer. He exposed himself to cigarette smoke almost 100 times a day – another well-known cancer causing agent.

LESSON READINGS

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W o r k b o o kLesson 1.1

MC Questions:

3. What is true about cancer?.a It is a fatal disease..c It is an infectious disease..d It is a disease of abnormal cells..d All of the above.

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DEFINITIONS OF TERMS

Cancer – a disease caused by an overgrowth of abnormal cells

with the capacity to spread to other parts of the body.

Oncology – the study of cancer as a disease.

Like many teenagers in the 60’s Diane Keaton, the Oscar-winning actress, describes herself as being “tan-obsessed”. She was undoubtedly not helped by tanning creams and lotions that were designed to increase sun exposure rather than protect from it. It is only as the ozone layer has become compromised that we have become aware how much UV radiation from the sun contributes to skin cancer developing. Diane Keaton paid the price for our lack of understanding when she was making critical choices that would impact her later health, but fortunately we all now have access to the informa-tion that sun exposure can be a cancer risk factor.

So even though cancer symptoms most frequently appear in older people, cancer can, and often does, originate when we are young. Fortunately we can make choices now that can influ-ence the later outcome. The challenge is to identify all the risk factors for cancer, so we can understand what all these choices might be, and to develop effective treatments for when a choice cannot be made.

What is cancer?

It was the Greek physician Hippocrates (of Hippocratic Oath fame) who came up with the name 'cancer'. Some of his patients had large red swellings under the skin with swollen blood vessels protruding from the bulge. Hippocrates thought that these swellings looked just like a crab digging into sand, so he called them karkinos, which was later modified to the Latin cancer. The study of cancer as a disease is called 'oncology' from the Greek word 'onkos', meaning 'swelling' or burden.

Figure 4: Advanced tumors such as the adrenal tumor above (left) are fed by swollen tubes of blood that look like legs on a crab (right: Blue King Crab). Our modern term 'cancer' is Latin for crab.

Figure 3: Diane Keaton was diagnosed with skin cancer at age 21. At that time sun creams promoted expo-sure to UV radiation rather than protecting from it.

LESSON READINGS

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W o r k b o o kLesson 1.1

MC Questions:

4. Which is the first stage of developing cancer?

.a Benign tumor;

.b Malignant tumor; or

.c Metastatic tumor.________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

5. True or false: Benign tumors always become metastatic tumors

.a True.

.b False.

DEFINITIONS OF TERMS

Tumor – a mass of rapidly growing cells.

Benign tumor – a tumor that is localized to a specific area of the

body and is not harmful.

Malignant tumor – a tumor that is capable of spreading to

surrounding tissues and organs and will cause disease.

Lymphatic system – the system of vessels that moves immune cells throughout the body. Like

the blood stream, but just for white blood cells.

Cancer is a disease caused by the rapid growth of abnormal cells which may initially form a swelling or tumor, but which eventually spread throughout the body. By the end of this module we will understand more clearly what causes drives the "abnormal" behavior.

What is the difference between cancer and a tumor?

It is important from the outset to understand that there is a critical distinction between a “tumor” and “cancer”. A tumor is simply an overgrowth of cells that form a mass. Tumors are quite common and remain local-ized in one place without causing disease. This kind of tumor is called a benign tumor. A clear example of a benign tumor is a wart or a mole.

On the other hand cancers are tumors that have evolved so they are now able to spread to other parts of the body. These mobile tumors are called malignant tumors. It is important to note that even malignant tumors are not necessarily life threatening. Some malignant cancers are not very mobile, and only spread a little within the tissue, behaving essentially like benign tumors. These kinds of tumors are detectable and

if the whole tumor is removed, the patient will be cured. It is tumors that migrate far away from the primary site so that they escape detection that are the most problematic.

Once cancers enter the blood stream or lymphatic system (the system that moves immune cells throughout the body) they are able to spread extensively throughout the body. This movement is called metastasis, from the Greek word for “next place”, and cancers that have acquired this ability are called metastatic tumors. Thus while all cancers are tumors, but not all tumors are cancers.

Figure 5: Warts (left) and moles (right) are two examples of benign tumors. They are localized and don’t cause severe disease.

Figure 6: Tumors can progress from benign (not harmful) to metastatic (cancer causing), but not all do. The challenge is identifying which benign tumors will become malignant.

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W o r k b o o kLesson 1.1

LESSON READINGSMC Questions:

6. Why is cancer so hard to treat?.a We haven’t spent enough money

on research;.b Scientists are lazy; or.c We don’t know what causes

cancer to spread.

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7. What is the most important question remaining in our understanding of cancer?

.a What causes cancer?

.b What causes tumors to spread?

.c What causes tumors to form?

.d All of the above are important.

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DEFINITIONS OF TERMS

Metastasis – the spread of ma-lignant tumor cells from the site of the primary tumor through blood/

lymph vessels.

Metastatic tumor – a cancer that has acquired the ability to enter the blood or lymph, and

spread through the body.

Why is cancer so hard to treat?

In 1971, President Nixon a plan to cure cancer within the next 30 years. Fifty years later after billions of dollars spent in research, we have made significant progress in the “War on Cancer” but by no means do we have a cure. Has the American public got value for money? Why has cancer been such a challenge?

We can only begin to answer this question if we have a clear idea how much our ideas about what cancer actually is have developed over the last fifty years. In fact the very notion that cancer as a disease evolves over time – benign tumors acquire the ability to become mobile and metastasize, becoming malignant in the process – is relatively recent. For more than thirty years our efforts focused almost exclusively on the primary tumors, failing to appreciate how insidious metastases can develop very early and become resistant to treatment. Thanks to the evolution in our understanding we can now appreciate that in order to treat a cancer successfully we need to have answers two fundamental questions:

■ When did the tumor first from?

■ When did the tumor spread?

It is not enough to be able to locate the primary tumor. Often times we first notice a tumor indirectly because it has disrupted bodily functions and caused symptoms such as breathlessness, pain and nausea. But at this point the tumor has often already metastasized and become resistant to treatment. It is critical to be able to identify a cancer before it metastasizes, which is often before it becomes symptomatic.

The notion that it is critical to understand the progression from benign tumor to metastasis raises another critical question: “How do we know which benign tumor will become metastatic?” We don’t need to treat benign tumors that will never be problematic. Conversely we also don’t want to ignore a tumor that might become metastatic. As we shall see in the next lesson (and in rest of the module), while our understand-ing of cancer as a disease has evolved significantly, until we can identify what causes a tumor to spread, the ultimate challenge – of curing cancer will remain.

STUDENT RESPONSES

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W o r k b o o kLesson 1.1

Remember to identify your sources

List 3-4 behaviors that you have heard that increase the risk of developing cancer, and what types of cancer they are linked to. To what extent are these behaviors under our control?

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W o r k b o o kLesson 1.1

TERMS

TERM DEFINITION

Benign tumor A tumor that is localized to a specific area of the body and is not harmful.

Cancer A disease caused by an overgrowth of abnormal cells with the capacity to spread to other parts of the body.

Lymphatic system The system of vessels that moves immune cells throughout the body. Like the blood stream, but for white blood cells.

Malignant tumor A tumor that is capable of spreading to surrounding tissues and organs and will cause disease.

Metastasis The spread of malignant tumor cells from the site of the primary tumor through blood/lymph vessels.

Metastatic tumor A cancer that has acquired the ability to enter the blood or lymph and spread through the body.

Mortality rate The rate at which people will die from a specific cancer.

Oncology The study of cancer as a disease.

Tumor A mass of rapidly growing cells in the body.

For a complete list of defined terms, see the Glossary.