Chapter 10

Cancer cells have other distinctive properties that set them apart and contribute to malignancy. Normal cells stop dividing once they come into contact with neighboring cells, a property called ____

contact inhibition

Finally, cancer cells promote the growth of new blood vessels, or ____, as a means of acquiring oxygen and nutrients for growth

angiogenesis

Aside from nonmelanoma skin cancer, ____ is the most common cancer affecting women worldwide

breast cancer

A decade ago, such operations would have seemed drastic and unwarranted. But over the years, the value of surgery to prevent future cancers has been validated by science. Studies in women with mutated BRCA genes who have not yet developed cancer show that ovary removal cuts the risk of ____ by 50% and the risk of ____ by 90%

breast cancer, ovarian cancer

For women with a mutation in BRCA1 or BRCA2, however, the risk is much higher: on average, these women have a 45% to 65% lifetime risk of developing ____ and a 10% to 40% risk of developing ____

breast cancer, ovarian cancer

When someone is born with a mutation in one copy of either BRCA gene—inherits it from mom or dad—that person's DNA repair system is...

compromised for their entire life

In other words, oncogenes are...

proto-oncogenes that have mutated to become permanently activated

The BRCA1 gene is located on ____

chromosome 17

Recall that each person inherits two sets of chromosomes and, therefore, two copies each of ____ and ____—one maternally inherited and one paternity inherited

chromosome 17, chromosome 13

Drugs called ____ are targeted therapies

PARP inhibitors

What are Proto-oncogenes?

A gene that codes for a protein that helps cells divide normally.

Ahern had a mutation in one of her copies of the ____ gene

BRCA1

Cells divide to replace cells lost in the injury process (T/F)

True

Though checkpoint mechanisms ensure that the vast majority of DNA replication mistakes are fixed, on average one uncorrected mistake occurs for every ____ DNA base pairs that are replicated

10 billion

Breast cancer is typically very rare in men, occurring in fewer than ____ men

1 in 1,000

Explain how Cell Replacement works in steps:

1. Cells in bone marrow regularly divide to produce new, healthy blood cells 2. The new cells migrate into the bloodstream to replace those that have reached the end of their lifespan

Immunotherapy includes:

1. Checkpoint inhibitors

What are the various types of cancer treatments?

1. Conventional therapy 2. Targeted therapy 3. Immunotherapy

For that reason, your best bet for avoiding cancer is to:

1. Don't smoke or chew tobacco 2. Eat healthy and maintain a healthful weight 3. Get vaccinated 4. Avoid harmful environments 5. Screen regularly for cancer 6. Get tested for hereditary cancers

Explain the Cell Cycle in steps:

1. During the cell cycle, one cell becomes two. A cell doesn't simply split in half, however. If it did, each resulting cell would be smaller than the original, and with each division, each cell would lose half its contents 2. Instead, before a cell divides, it first makes a copy of its contents so that each new cell has the same amount of organelles, DNA, and cytoplasm as the original cell. This preparatory stage of the cell cycle, called interphase, is divided into three subphases: G1, S, and G2 3. During the G1 phase, the cell grows larger and begins to produce more cytoplasm and organelles 4. During the synthesis phase (S), the cell's DNA is replicated—which means that its chromosomes are duplicated. A replicated chromosome consists of two identical DNA molecules, known as sister chromatids; initially, this set of two sister chromatids is linked at their midpoint 5. During the G2 phase, the cell prepares to enter the division phases. Different cell types divide at different rates—some very fast, some very slow. In a cell that takes approximately 24 hours to divide, interphase takes about 22 hours to complete 6. Once the cell duplicates its contents, it enters the two division phases of the cell cycle: mitosis, in which the sister chromatids of each replicated chromosome become evenly divided between the two daughter cells; and cytokinesis, in which the two daughter cells physically separate 7. Once the cell is finished dividing, it may enter a resting phase of the cell cycle, called G0. During G0, the cell goes about its business as usual, but is not preparing to divide. Some cells in the body, like adult nerve cells, are in a permanent state of G0

At least one checkpoint is found in each phase of the cell cycle:

1. G1 2. G2 3. S 4. Mitosis

Targeted therapies include:

1. PARP inhibitors

What are the phases of Mitosis?

1. Prophase 2. Metaphase 3. Anaphase 4. Telophase

Mutations in BRCA genes are an important driver of both inherited and sporadic cancer, but they aren't the only ones. There are hundreds of known genes that can promote cancer when they are mutated. Most of these genes can be categorized into one of two types:

1. Proto-oncogenes 2. Tumor suppressor genes

Conventional therapy includes:

1. Surgery 2. Chemotherapy 3. Radiation

With genetic testing for BRCA and other mutations becoming increasingly common, more and more people find themselves facing a difficult choice:

1. Wait to see if they develop cancer 2. Take proactive action

For most men, the risk of developing prostate cancer is about one in eight, or ____

12%

For most women, the lifetime risk of developing breast cancer is about ____, or 1 in every 8 women

12%

For most men, the risk of developing prostate cancer is about one in eight, or 12%. But for men with a BRCA mutation, that risk is one in four, or ____

25%

More than ____ women in the United States are diagnosed with breast cancer each year, according to the National Cancer Institute

250,000

Doctors recommend that women without a family history of breast cancer begin getting mammograms at age ____ or ____. For women with such a history or a known BRCA mutation, earlier mammograms are recommended

45, 50

But in men with a BRCA mutation, the risk rises to...

5% to 10

Scientists estimate that inherited mutations in genes like BRCA1 or BRCA2 account for about ____ to ____ of all cancers

5%, 10%

Explain Embryonic Development

A fertilized egg and its daughter cells continue to divide to create the trillions of cells that make up the human body

Though checkpoint mechanisms ensure that the vast majority of DNA replication mistakes are fixed, on average one uncorrected mistake occurs for every 10 billion DNA base pairs that are replicated. That may not seem like a lot, but consider this: each human cell has...

6 billion total base pairs, and some body cells divide trillions of times in our lifetimes. With so many opportunities for something to go wrong, the number of mutations that can occur in any given cell quickly adds up

Scientists estimate that inherited mutations in genes like BRCA1 or BRCA2 account for about 5% to 10% of all cancers. The other ____ to ____ of cancers are caused by mutations that occur during a person's lifetime

90%, 95%

What are Targeted Therapies?

A cancer therapy that is specific for cancer cells and not harmful to normal cells

What are Immunotherapies?

A cancer therapy that uses the immune system to recognize and destroy cancer cells

What is a Malignant Tumor?

A cancerous tumor whose cells can spread throughout the body

What are Cell Cycle Checkpoints?

A cellular mechanism that ensures that a stage of the cell cycle is completed accurately

What is Contact Inhibition?

A characteristic of normal cells that prevents them from dividing once they have filled a space and are in contact with their neighbors

What is Cancer?

A disease in which cells divide repeatedly and without restraint, in some cases forming a tumor

What are Tumor Suppressor Genes?

A gene that codes for a protein that monitors and checks cell cycle progression. When these genes mutate, tumor suppressor proteins lose normal function

What is a Tumor?

A mass of cells resulting from uncontrolled cell division

What is a Benign Tumor?

A noncancerous tumor whose cells will not spread throughout the body

Normal cells with functioning BRCA proteins can repair DNA damage in the presence of ____, but BRCA-mutant cells cannot and consequently die

PARP inhibitors

Explain how Tumors Develop in Stages as Mutations Accumulate in a Cell:

A. Inherits BRCA1 mutation: DNA damage will not be efficiently repaired. Additional mutations are more likely to occur and be passed to additional cells during cell division (green cells) B. A carcinogen damages DNA and produces an oncogene: the oncogene is overactive, allowing the cell to divide more often without normal checks. Cells begin to pile up into a tumor C. Smoking mutates tumor suppressor genes: cells fail to correct DNA damage or enter apoptosis. Cells have lost contact inhibition, dividing even when crowded D. Additional mutations permit metastasis and new blood vessel growth: the tumor contains malignant cells that lose their connections with the tissue, allowing them to invade surrounding tissues and spread to nearby and distant locations in a process called metastasis. The cells of the tumor also promote new blood vessel growth, allowing delivery of oxygen and nutrients

What is a Mammogram?

An x-ray of the breast

Actress ____ made headlines in 2013 when she elected to undergo a double mastectomy as a preventive measure

Angelina Jolie

What are Carcinogens?

Any substance that causes cancer. Most carcinogens are mutagens

Although any family may carry mutated BRCA1 or BRCA2 genes, certain ethnic groups are more likely than others to have them. Ahern's background is ____, meaning that her ancestors were Jews of German and Eastern European descent

Ashkenazi Jewish

____ kill cancer cells specifically by exploiting weaknesses caused by oncogenes or mutated tumor suppressor genes

Targeted therapies

Drugs called PARP inhibitors are an effective treatment for...

BRCA-mutated cancers, including breast, ovarian, prostate, and pancreatic cancers

In some families with particular ____ mutations, the risk of getting breast cancer can run as high as 80%

BRCA1

Jolie had tested positive for a ____ mutation, and her mother, grandmother, and aunt had all died of either breast or ovarian cancer

BRCA1

By the middle of the decade, scientists had isolated the specific mutated gene, which they called ____, and determined its function. Identification of ____ occurred soon thereafter

BRCA1, BRCA2

There was more bad news in store for Ahern. About a year after she received the diagnosis of breast cancer, Ahern had DNA extracted from her blood and tested for mutations in two genes—____, located on chromosome 17, and ____, located on chromosome 13

BRCA1, BRCA2

BRCA stands for?

Breast Cancer

____ cells have an irregular shape, often with membrane extensions (green) that enable rapid crawling

Breast cancer

Explain Metastasize

The spread of cancer cells from one location in the body to another

____, a gene frequently mutated in certain types of breast cancer, is an example of a proto-oncogene. It provides a "go" signal for cell division when a growth signal is present

HER2

Men are also affected by mutations in the two BRCA genes (T/F)

True

What causes cells to "go rogue"?

Cancer results when cells accumulate DNA sequence changes—mutations—that interfere with the orderly steps of the cell cycle

Explain the word Sporadic

Cancers that are caused by non-inherited (acquired) mutations

There are many strategies to treat cancer. ____ and ____ kill rapidly dividing cells in the body, including cancer cells

Chemotherapy, radiation therapy

____ are generally nonspecific, in that they can harm normal cells as well as cancer cells

Conventional therapy

Explain what happens in mutated Proto-Oncogenes

Growth signals are not present. Ocogene proteins are permanently activated. Cell cycle progresses

Explain what happens in normal Proto-Oncogenes

Growth signals are recognized. Proto-oncogene proteins are produced. Cell cycle progresses

Mutated tumor suppressor genes allow the cell to continue to divide, even if there is...

DNA damage

A person who inherits a mutation in one copy of the BRCA1 or BRCA2 gene starts life with at least one cancer-predisposing mutation. As a result, he or she requires fewer additional mutations to develop cancer. Moreover, because it disrupts DNA repair, a single mutation in a BRCA gene is enough to increase the chances that additional mutations will occur in that cell:

DNA damage caused by a replication error or exposure to carcinogens will go unrepaired—or be repaired incorrectly—leading to a permanent change in the nucleotide sequence of DNA. Daughter cells will accumulate mutations at a faster rate, which is why hereditary cancers often strike people who are in their 30s and 40s—much younger than people who have no inherited predisposition to cancer. Typically, by the time a person with an inherited predisposition develops cancer, their other (normal) copy of the BRCA gene will have been mutated as well

Explain what happens in mutated Tumor Suppressor Genes

Damage is not recognized. Cell cycle is not paused and damage is not repaired. Apoptosis is not initiated

Explain what happens in normal Tumor Suppressor Genes

Damage is recognized. Cell cycle is paused and damage is repaired. If damage cannot be repaired, apoptosis is initated

____ proteins don't do their jobs, so additional mistakes continue to accumulate in these cells

Defective checkpoint

____ cuts the risk of breast cancer by 95%

Double mastectomy

____, like smoking, infections, or a bad sunburn, can also damage DNA

Environmental insults

____ are critical in regulating cell division

Growth factors

The drug ____ blocks this overactive HER2

Herceptin

Explain Telophase

Identical sets of chromosomes reach each pole. Microtubule spindle fibers disassemble. A nuclear membrane forms around each set of chromosomes, forming the daughter cell nuclei

____ are drugs or treatments that stimulate the body's own immune system to find and fight cancer within the body. For some types of cancer—including melanoma, lung, and kidney cancer—this approach has proved very effective

Immunotherapies

____ stimulate the immune system to find an attack cancer

Immunotherapy

People born with certain mutations in the genes BRCA1 or BRCA2 have a higher risk of developing cancer than people born with normal versions of the BRCA genes (T/F)

True

Explain Repairing Damaged Tissue

Injury triggers cell division to replace damaged cells

Explain Metaphase

Microtubule spindle fibers from opposite ends of the cell attach to the sister chromatids of each chromosome. Replicated chromosomes become aligned along the middle of the cell

Explain Anaphase

Microtubules shorten, pulling the sister chromatids to opposite ends of the cell

____ is the complex and carefully orchestrated process by which a dividing cell imparts the correct number of chromosomes to each daughter cell

Mitosis

What is the difference between Mitosis and Cytokinesis?

Mitosis is the division of the nucleus, while cytokinesis is the division of the cytoplasm

Explain Cell Replacement

Most cells have a finite life span. Cell division within tissues regularly replaces the dying cells and maintains health tissues

____ in these genes push the cell to divide, even in the absence of these signals

Mutations

Explain Prophase

Replicated chromosomes begin to coil up. The nucleic membrane begins to disassemble. Microtubule fibers begin to form the mitotic spindle

____ are designed to kill cancer cells specifically. Often they combat a specific defect in the cancer cell, such as the mutated protein made from an oncogene or tumor suppressor

Targeted therapies

Are Ashkenazi Jews most likely than the general population to carry mutations in BRCA1 and BRCA2?

Some studies have found that approximately 3% of Ashkenazi women carry a mutated BRCA1 gene, compared to 0.2% of other women. For that reason, doctors may recommend that Ashkenazi Jewish women get genetic testing to determine if they carry a BRCA mutation

There are many strategies to treat cancer. ____ removes a tumor or at-risk tissue

Surgery

____ is generally effective for solid tumors that are diagnosed early, but not for cancers that have spread to other parts of the body, or for cancers that do not produce tumors, like leukemia

Surgery

Why do chemotherapy and radiation cause severe side effects?

That's because neither therapy is very specific—both treatments damage all dividing cells in their path, including healthy ones. In particular, chemotherapy routinely kills healthy cells lining the intestinal tract, cells in hair follicles, and cells in the bone marrow. These cells share a common property: they all normally divide frequently. The side effects of these unintended cell deaths can include vomiting, bruising, hair loss, and susceptibility to infection

What is Angiogenesis?

The growth of new blood vessels

What is the Mitotic Spindle?

The microtubule-based structure that separates sister chromatids during mitosis

What is Anchorage Dependence?

The need for normal cells to be in physical contact with another layer of cells or a surface

What is the Cell Cycle?

The ordered sequence of stages through which a cell progresses to divide. The stages include preparatory phases (G1, S, G2) and division phases (mitosis and cytokinesis)

What is Cytokinesis?

The physical division of a cell into two daughter cells

What is Cell Division?

The process by which a cell reproduces itself; cell division is important for normal growth, development, maintenance, and repair of an organism

What is Mitosis?

The segregation and separation of replicated chromosomes during cell division

What is the Centromere?

The specialized region of a chromosome where the sister chromatids are joined; it is critical for proper alignment and separation of sister chromatids during mitosis

What is the Interphase?

The stage of the cell cycle in which dividing cells spend most of their time, preparing for cell division. There are three distinct subphases: G1, S, and G2.

What is are Sister Chromatids?

The two identical DNA molecules that result from the replication of a chromosome during the S phase

What is Radiation Therapy?

The use of ionizing (high-energy) radiation to treat cancer

Explain BRCA1 and BRCA2

These genes encode proteins that are important for repairing damaged DNA. Women who are born with mutations in one copy of either of these two genes have a much higher risk of developing breast and ovarian cancers

All cancers do share something in common:

They take advantage of what our bodies have evolved to do normally—grow and repair themselves through cell division

What does it mean if Ahern had a mutation in one of her copies of the BRCA1 gene?

This meant that her breast cancer was likely caused by this mutation and could put her at high risk for developing a second cancer. Moreover, her children might also be at risk, if they inherited the mutation. When genetics are to blame, cancer can run in the family

What is Chemotherapy?

Treatment using toxic chemicals that kill cancer by interfering with cell division

____ encode proteins that normally prevent cell division when problems arise that need to be corrected. These "stop" signals may pause cell division, repair damaged DNA, or initiate apoptosis

Tumor suppressor genes

In the ____, one in two men and one in three women will develop cancer in their lifetimes

United States

What is Apoptosis?

When a normal cell sustains irreparable damage, it undergoes programmed cell death. This cellular suicide prevents cells from producing more damaged daughter cells

____ with one copy of a mutated version of either BRCA gene are at higher risk of developing breast cancer and ovarian cancer in their lifetime

Women

Normal cells also usually require connections to the tissue to which they belong, property called ____

anchorage dependence

If a proto-oncogene is mutated, it's as if the...

accelerator is stuck down and cell division keeps going, even if the cell should not be dividing

Checkpoints prevent a cell from progressing to the next stage until it...

accurately finishes the current stage

Cancer cells have more copies of the HER2 protein, which becomes...

active even without a growth signal

Regulated cell division ensures that...

adequate cell numbers and healthy tissue structure are maintained in the body

At one checkpoint, for example, proteins scan DNA for damage or incorrect base pairing. Another checks that chromosomes are properly aligned in mitosis. If problems are detected, one of two things happens: either the cell pauses the cycle and gives itself time to fix DNA mistakes, or, in the case of severe and irreparable damage, the checkpoints direct a cell to commit suicide in a process called ____

apoptosis

What scientists are learning about inherited mutations may also...

apply to those who acquire mutations over their lifetime

Normally, cells divide only in response to...

appropriate growth signals relayed by molecules known as growth factors

The collection of mutated genes can include a combination of tumor suppressor genes that have lost their function and proto-oncogenes that have been activated to become oncogenes. The need for multiple hits is the main reason cancer affects people more as they age:

as cells accumulate mutations over time through exposure to carcinogens and repeated rounds of cell division, the chances increase that a cell will accumulate enough mutations to become cancerous

After one or two genetic hits or mutations, a dividing cell may form clump of cells called a ____

benign tumor

If a tumor suppressor gene is mutated, it's as if the...

brakes don't work and the cell division cannot be stopped, even if problems occur

"You can think of tumor suppressors as ____ and the oncogenes as the ____," says Thomas Sellers, a cancer biologist at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. "They are sort of the yin and yang of each other."

brakes, accelerators

Women with one copy of a mutated version of either BRCA gene are at higher risk of developing breast cancer and ovarian cancer in their lifetime. Men with these mutations are also at higher risk of developing...

breast and other cancers, including prostate cancer

In these cases, the best option is usually ____—using toxic chemicals to kill the cancer cells in the body

chemotherapy

Lorene Ahern of Twinsburg, Ohio, wasn't totally surprised when she was diagnosed with breast cancer. "Half of me was expecting it all my life and part of me was saying, 'No, this won't happen to me,' " says the 47-year-old mother of two. She knew that her risk of cancer might be higher than average—her mother had died of cancer at 49. But until the day she was diagnosed, Ahern, who took good care of herself and had a healthy lifestyle, had never fully believed she would develop ____, a disease in which cells divide repeatedly and without restraint

cancer

Through genetic testing, people can learn whether they have a mutated copy of a particular gene, such as the BRCA1 or BRCA2 gene. When these genes are mutated, a person has an increased risk of developing ____

cancer

When cells accumulate enough mutations to interfere with multiple checkpoints, the result is ____

cancer

Substances that are known to cause cancer, or increase its risk of forming, are called ____

carcinogens

The downside of both chemotherapy and radiation is that they can...

cause severe side effects

To produce new cells by cell division, cells pass through a series of stages collectively known as the ____

cell cycle

Cells have a natural barrier against the accumulation of mutations: a system of ____ that monitors the cell's progress through the cell cycle and prevents cells from moving into the next phase if problems arise

cell cycle checkpoints

Normal cells have mechanisms to ensure that...

cell division is carried out accurately and only when necessary

During childhood, cell division helps us grow larger. As we age, our tissues continually discard old cells and generate new ones in their place. And when we cut or injure ourselves...

cells in the area divide to heal the wound. For nearly all cells—with the possible exceptions of adult nerve cells and heart muscle cells—cell division is a regular part of life

Having only one functional copy of either BRCA gene means that the person has a lower capacity to repair DNA. As a result...

cells throughout their body are prone to accumulating DNA mistakes at faster rates than the cells of someone who did not inherit a BRCA mutation and has two working copies of the BRCA proteins

You can think of mitosis as a carefully choreographed dance of chromosomes. At the beginning of the dance, the replicated chromosomes, each with two sister chromatids, are present in the nucleus as loosely gathered threads. To avoid becoming entangled, the chromosomes condense into tightly wrapped, rod-shaped structures that can move about the cell more easily. The two identical sister chromatids of a replicated chromosome are held together at a region called the _____

centromere

Several forms of immunotherapy are available. In one common approach, drugs called ____ are used to temporarily release a natural brake on immune cells that keeps the immune system in check. Once this brake is released, the immune cells can find and attack the cancer. Some cancers actively engage this brake to avoid being killed by immune cells. By releasing the brake, the checkpoint inhibitor robs the cancer of its defenses. These drugs can sometimes have serious immune-related side effects, and not everyone responds to them, but individuals who do can sometimes experience dramatic improvements in their cancer

checkpoint inhibitors

The BRCA2 gene is located on ____

chromosome 13

The bad news is that prevention is not that simple for people with inherited predispositions to cancer. For this group, diet and lifestyle changes make less of a difference. As scientists have learned, a genetic mistake stacks the deck against them by...

creating biological conditions that make developing cancer more likely. What's more, even after receiving treatment for cancer, people with mutations in one of the BRCA genes are at risk of developing a second cancer, such as in the other breast

The ovaries are a major source of estrogen in the female body. Removing this source of estrogen...

cuts down on cell division in breast tissue, thereby reducing the likelihood that mutations in breast cells will occur

During cytokinesis, the ____ divides

cytoplasm

When a cell divides, each ____ cell must receive the correct number of chromosomes—in humans, that means no more and no less than a complete set of 46 chromosomes

daughter

A single fertilized egg cell divides, and its...

daughter cells divide again and again, eventually forming trillions of cells by the time a baby is born

The purpose of the cell cycle is to replicate cells, creating two new...

daughter cells that are genetically identical to the original parent cell

Cancer cells typically lose anchorage dependence as well, so they are able to...

detach from their neighboring cells and spread

Cell division is a normal part of...

development, growth, maintenance, and repair of the body

Proto-oncogenes push the cell to...

divide when the appropriate signals are present

In their normal form, the BRCA1 and BRCA2 proteins help repair DNA damage—specifically, ____, in which both sides of the DNA "ladder" are broken. They spring into action when a checkpoint detects this type of DNA damage and help correct it. When these proteins are mutated, cells can no longer properly repair this damage adequately. As a result, additional genetic mistakes—more mutations—accumulate in these cells, eventually leading to cancer

double-strand breaks

The good news is that studies have shown that diet and lifestyle changes can...

dramatically cut a person's risk of developing many types of cancer—just quitting smoking reduces the risk by 30%

PARP inhibitors block the activity of an ____ that contributes to DNA repair

enzyme

Genetic testing is performed by...

extracting DNA from the nuclei of white blood cells and looking for mutations in the genes of interest

A ____ cell and its descendants divide repeatedly to generate the cells that make up a newborn

fertilized egg

It takes more than a single mutation to cause cancer. Individuals who have inherited high-risk mutations require...

fewer additional mutations to get to cancer, and therefore develop cancer at a much earlier age

Toward the end of mitosis, the spindle fibers then shorten to pull each sister chromatid away from its partner to the opposite side of the cell. Each chromatid will eventually...

form one of two genetically identical chromosomes—one for each daughter cell

However, the same gene mutations that can predispose a person to cancer when they are inherited are often...

found in sporadic cancers, too

If any chromosome is left out of a daughter cell, all the...

genetic information contained in that chromosome will be missing, which could spell disaster for the cell.

A ____ can ascertain whether a person carries any of the high-risk BRCA mutations.

genetic test

In addition, the more scientists learn about how BRCA mutations increase cancer risk in some people, the better they are...

getting at treating cancer in all people

Proto-Oncogenes are...

go signals

Cancer cells, unlike normal cells, divide even in the absence of...

growth factors and without stopping. In essence, cancer is cell division run amok

The ____ vaccine, for example, prevents the infections that cause a large proportion of genital cancers and head and neck cancers—provided people get the vaccine when they are children, before they are exposed to the virus

human papillomavirus (HPV)

Normal proto-oncogenes activate cell division, but only...

in response to appropriate signals from growth factors

The accumulation of unrepaired DNA mistakes greatly...

increases an individual's risk of developing cancer

A small minority of cancers run in families, due to...

inheritance of mutations in cancer-associated genes

Most chemotherapy drugs work by...

interfering with one or more steps of the cell cycle in dividing cells

The cell cycle consists of preparatory phases collectively known as...

interphase, as well as the division phases, mitosis and cytokinesis

Cell division is a normal part of the development, growth, maintenance, and repair of the body. In fact, cell division in our bodies begins...

long before we are born

Some benign tumors remain benign, but others can turn cancerous. After several more mutations occur in this population of genetically abnormal cells, a ____ may result

malignant tumor

Screening is also very important to detect cancers early. Because tumors in the breast are hard to detect by a breast self-exam alone, the best primary screening method is a ____, an x-ray of the breast

mammogram

One reason why cancer is so hard to beat is that it is not one disease, but...

many. Different tissues develop cancer as a result of different mutations, and the body has more than 200 different tissues

For many types of cancer, the first line of treatment is surgery to remove the tumor. In the case of breast cancer, that can mean complete removal of the breast, called a ____. Alternatively, a surgeon may remove just the tumor plus a small amount of surrounding tissue, a procedure called a ____

mastectomy, lumpectomy

Malignant tumors have the capacity to ____—that is, they can spread to other locations in the body and form new tumors there

metastasize

The mitotic spindle is made up of ____, the same protein fibers that make up part of the cell's cytoskeleton

microtubules

Mistakes can happen at any point in the cell cycle, but those that occur during ____ can be especially catastrophic

mitosis

The cellular machine that orchestrates all this pushing and pulling is called the ____

mitotic spindle.

Cells in a benign tumor divide...

more frequently than do cells in normal tissues, but they do not spread to other areas and so are usually much less dangerous

It usually takes more than a single mutation in a cell to cause cancer. In most cases, a cell will become cancerous only after it has acquired multiple mutations in several genes that regulate the cell cycle or repair DNA damage. This is known as the ____, in which each "hit" is a mutation, and multiple hits are needed to cause the disease

multi-hit model of cancer

Most carcinogens are also ____—physical or chemical agents that cause mutations in DNA.

mutagens

Doctors have known for decades that breast cancer runs in certain families: a woman's chance of getting the disease is greatly increased if she has a sister or mother who has it. But it wasn't until the 1990s that researchers homed in on the reason:

mutations in a particular region of chromosome 17 are unusually common in these families

Why mutations in BRCA genes tend to cause only certain types of cancer—such as breast, ovarian, and prostate cancers, for example, but not lung or colon cancer—is...

not yet understood

The DNA sample for testing is extracted from the ____ of ____. The BRCA1 gene is located on chromosome 17. The BRCA2 gene is located on chromosome 13.

nuclei, white blood cells

When proto-oncogenes are mutated, they can become permanently turned on, stimulating cells to divide all the time, even in the absence of appropriate signals from growth factors. In this state they are called ____—literally, "genes that cause cancer."

oncogenes

In 2015, Jolie went further and had her ____ removed as well

ovaries

When it came time for treatment, Ahern chose a lumpectomy to remove her breast tumor, followed by chemotherapy and radiation. But she also did something less conventional: she had her ____ removed

ovaries

More than 50% of all cancers have a mutation in the ____ tumor suppressor gene, for example

p53

As genetic mutations accumulate, cancerous cells usually lose the contact inhibition property. The result is a...

pile of cells growing on top of each other

Tumor suppressor genes act to detect...

problems (such as DNA damage) and pause the cell cycle, or cause the cell to carry out apoptosis

Cell cycle checkpoints regulate a cell's...

progress through the cell cycle

As mitosis progresses, these linked sister chromatids move across the cell and line up along the midline of the cell. Once they are aligned, the two sister chromatids of each chromosome will eventually be...

pulled apart and dragged to different sides of the cell. As a result, when the cell goes through cytokinesis, each of the two daughter cells will have one of each sister chromatid

For both men and women, BRCA mutations more than...

quadruple the risk of developing pancreatic cancer, the deadliest of all cancers

Doctors may also treat a tumor with ____

radiation

In ____, beams of ionizing (high-energy) radiation are focused on a tumor. The radiation damages DNA in dividing cells. Cancer cells are less able to repair this DNA damage than are normal cells, so they die

radiation therapy

Specialized cells in tissues divide to...

replace cells that have reached the end of their lifespan

Mutations can happen in a variety of ways. Every time a cell ____ its DNA, for example, there is a small chance that it will make a mistake—insert the wrong nucleotide, for instance

replicates

The cancer itself is not inherited, but the...

risk of getting it is

By being aware of risk factors for cancer, people can minimize their exposure and therefore reduce their risk of developing cancer. Other preventive strategies include...

screening and genetic testing for people with a family history of cancer

Cancer is the ____ leading cause of death among both men and women in the United States, right after heart disease

second

During cytokinesis, the two nuclei become...

separated into daughter cells

When tissue is damaged, growth factors are released. These growth factors...

signal cells in the area that they need to divide to repair the damage

At the beginning of mitosis, microtubule spindle fibers extend from each end of the cell and snag the centromere region of each chromatid, such that each chromatid in a chromosome is attached to a spindle fiber extending from the opposite end of the cell. By alternating between lengthening and shortening, the...

spindle fibers move the attached chromosomes until they are aligned at the midpoint of the cell

The vast majority of cancers are ____—caused by mutations that are acquired over the course of one's life

sporadic

Therefore, the vast majority of cancers are ____, rather than inherited.

sporadic

Tumor Supressor Genes are...

stop signals

Without a properly functioning p53 protein, cells cannot commit...

suicide in response to DNA damage, and mutations accumulate in cells as a result

As estrogen is also produced in small amounts by other organs, Ahern takes an estrogen-blocking drug called ____ as well. All of these treatments are designed to reduce the chance that the cancer will recur in her body

tamoxifen

Newer treatment approaches specifically...

target cancer cells or improve the ability of the immune system to recognize and attack cancer cells

In recent years, new forms of cancer treatment have become more common, including ____ and ____

targeted therapy, immunotherapy

Though cancers originate from a single cell that has "gone rogue," cancerous tumors do not emerge in a full-blown state overnight. Instead, they...

tend to develop in stages, becoming more aggressive over time

Metastasis is the main way...

that cancer kills

Women who, like Ahern, have a genetic predisposition to getting cancer are often said to have "hereditary" or "inherited" cancer. This does not mean that their cancer was passed from parent to child, the way that eye or hair color is. Instead, it means...

that they have inherited a genetic mutation, from one or both parents, that makes the development of cancer much more likely

Equally important, mutations will accumulate faster if the proteins that monitor and repair DNA damage or trigger apoptosis are...

themselves damaged by mutation

Tumor suppressor genes cause cancer when...

they are inactivated by mutation

The BRCA proteins are also tumor suppressors as...

they help repair DNA damage

Though we tend to think of our bodies as relatively fixed structures, most of our ____ are in constant flux as cells divide periodically to replace those cells that have reached the end of their life span

tissues

According to the American Association for Cancer Research, more than half of all cancer deaths each year are related to preventable causes. At the top of the list is...

tobacco use, followed closely by obesity and cancer-causing infections

Cancer cells plow through the cell cycle unimpeded, divide uncontrollably, and in many cases eventually form a mass of cells called a ____

tumor

When cells no longer need to divide—for example, when a wound has healed or when worn-out tissues have been replaced—the growth signals are...

turned off and cells take a break from dividing

If inherited mutations account for only a small fraction of cancers (about 5% to 10% of the total), that means that most cancers are the result of mutations...

we acquire during our life. Some of these mutations can be avoided by engaging in a healthy lifestyle—in other words, we have some control over them

Cell division also acts to replace damaged cells in ____

wounds