CRC Biology
Colorectal cancer (CRC) is the third most common cancer in men and women1, usually diagnosed in people aged 50 years or older.2 If colorectal cancer is not found at its earliest stages through preventative screenings, it can develop into metastatic colorectal cancer (mCRC), which is an advanced stage of disease.3 There are new treatments if you have this condition.
Understanding the Colon & the Rectum
The colon and the rectum are parts of the digestive system4 and make up the large intestine.5 The first 4 to 5 feet of the large intestine make up the colon, and the rectum is the last 7 inches.6 Food is digested as it travels through the small intestine and then enters the colon, which removes water and nutrients from the food and then stores the rest as waste (stool). The waste passes through the colon, into the rectum and then out of the body through the anus.7
The wall of the colon and rectum consists of multiple layers. Colorectal cancer starts in the innermost layer and may grow through other layers if it progresses.8
How Cancer Forms
Multiple factors have been shown to influence the development of cancer, including genetic, hereditary and environmental.9 Research demonstrates that familial history plays a role in up to 25% of patients diagnosed with colorectal cancer.10,11 Chronic inflammatory disorders of the digestive track also increase the risk of developing CRC.12 Colorectal cancer typically develops from a polyp, a benign (non-cancerous) tumor or tissue growth, in the inner lining of the colon or rectum. There are different kinds of polyps and some can become malignant (cancer).

You can take an active role in understanding your condition in
order to work with your doctors and manage your treatment.
References
Types of Polyps
Most colorectal cancers first develop from colorectal polyps, abnormal growths inside the colon or rectum that develop silently. Catching these polyps early through regular screenings by your doctor can prevent the development of CRC.

Polyps are small masses of cells that can develop anywhere along the inner lining of the colon and rectum. Type, location, size, and number of polyps are related to risk of developing cancer.

2. Sessile polyps sit right on the surface of the mucous membrane. They are elevated but do not have a stalk.
3. Pedunculated polyps are mushroom-like tissue growths that are attached to the surface of the mucous membrane by a long, thin stalk, or peduncle.
The most common types of colorectal polyps are ademonas, serrated, and post inflammatory.
Villous or Tubulovillous Adenoma
This type represents approximately 15% of ademonas that are found and removed with colorectal cancer screening – they have the highest likelihood of developing into colorectal cancer.
♦ Smoke
♦ Eat a high-fat and low-fiber diet
♦ Are overweight
♦ Have a personal or family history
with CRC, colon polyps or
inflammatory bowel diseases

Polyps form as a result of abnormal tissue growth,13 which is typically due to genetic alterations. The intestine has a higher tissue turnover rate than many other organs in the body, which creates greater opportunity for development of abnormal tissue and cancer cells.14
There are two general groups of genes that control the process of cells growing and dividing.15 If any of these genes mutate, it can cause cells to continue dividing and form abnormal tissue, such as polyps in the colon or rectum. Polyps are likely to become malignant if this unregulated growth continues for an extended period of time,16,17 though colorectal cancer typically takes several years,18 or even decades,19 to develop.
Metastatic Cancer
Once cancer forms in a polyp, it gradually progresses into the wall of the colon or rectum and can then grow into blood vessels or lymph vessels. Lymph vessels are thin tubes, similar to veins, that carry fluid and debris.20 They drain into nearby lymph nodes, which are small structures with immune cells that filter harmful substances and help fight infections.21 Cancer cells can spread to nearby lymph nodes or other parts of the body by traveling through the blood or lymph vessels.22
The spread of the cancer to other parts of the body is called metastasis.23 Colorectal cancer commonly spreads to the lungs,24 liver25 and bone.26
Tumor Angiogenesis
Understanding Angiogenesis
Angiogenesis, the growth of new capillary blood vessels, is an important natural process in the body used for healing and reproduction. The body controls angiogenesis by producing a precise balance of growth and inhibitory factors in healthy tissues.
When this balance is disturbed, the result is either too much or too little angiogenesis. Abnormal blood vessel growth, either excessive or insufficient, is now recognized as a “common denominator” underlying many deadly and debilitating conditions, including cancer, skin diseases, age-related blindness, diabetic ulcers, cardiovascular disease, stroke, and many others. The list of diseases that have angiogenesis as an underlying mechanism grows longer every year.
Angiogenesis and Cancer
All cancers, including CRC, require the growth of new blood vessels to grow beyond a few millimeters in size. These new blood vessels supply the tumor with the oxygen and nutrients needed to grow, and act as lifelines to cancer cells.
A major advance in cancer treatment in recent years has been the development of drugs, called angiogenesis inhibitors, or antiangiogenic drugs, which are designed to target and interfere with the tumor blood supply, in essence, to ‘starve’ cancer cells. These treatments can slow or stop tumor growth. Learn more about the specific targeted treatments here.
A tumor in its early stages of development cannot grow past a few milimeters in diameter unless it is fed by blood vessels. Angiogenesis – the growth of new blood vessels – is essential for tumor growth and spread.
of growth
factors
1. Cells in the center of the tumor mass have to compete with their neighboring cells for access to oxygen and nutrients. When they begin to starve, they release growth factors as a “distress signal” to the surrounding tissue.
sprouting
2. Nearby blood vessels receive these signals and begin to grow new vessels toward the source. As long as the signal continues, the vessels will continue to grow in its direction.
feeding tumor growth
(metastasis)
3. Vessels that grow into the tumor nourish the tumor tissue, delivering oxygen and essential nutrients. As the tumor grows larger, signaling may increase and encourage even more blood vessel growth.
4. The tumor expands and invades surrounding tissue. Cancer cells spread as metastases through the blood vessels and lymph nodes, first locally then to distant organs in the later stages of CRC progression.
CRC Staging
Staging of cancer is the process doctors use to identify the extent and location of the cancer, including whether it has spread to other areas in the body. This information is used to plan the most effective treatments for each patient. Treatments can differ based on the stage of disease.27
The most common variables considered in staging systems include the site of the primary (original) tumor, size and number of tumors, the spread of cancer into lymph nodes, how similar cancer cells are to normal cell tissue, and whether the cancer has metastasized.28

The stage of a cancer is designated at the time of diagnosis. It never changes, even if the cancer progresses. A cancer that spreads or reoccurs is still referred to by the stage it was given when it was first diagnosed, with information about the current extent of the cancer added to it.30
Doctors gather different types of information about a cancer to determine its stage. The exact tests used for staging depend on the type of cancer.31
Common tests include:
- Physical exams and imaging tests help to evaluate the extent of the cancer by identifying the location and size of the tumor(s) and whether the cancer has spread to the lymph nodes or to other parts of the body. Imaging tests such as MRI or CT scans, or x-rays, show pictures of the tumor.
- Laboratory tests use samples of blood and other bodily fluids or tissues to gather information about the cancer.
- Pathology reports provide information about the size of the tumor, the extent of the spread of the cancer into other areas of the body, the type of cancer cells and the tumor grade (how the cells differ from normal cells). Samples of the tumor help to diagnose and stage the cancer.
- Surgical reports use tumor samples taken during surgery to identify the size and type of tumor, and the extent of lymph node or organ involvement.
The doctor most familiar with your situation is in the best position to assess the stage of your cancer.32
If colon cancer is found, it is highly treatable in its early stages. If the cancer spreads into nearby lymph nodes, chemotherapy followed by surgery has been a highly successful combination treatment.
In the most difficult cases — when the cancer has metastasized to other organs, such as the liver or lungs — treatment can prolong life.33

TNM Classification
TNM Classification is the most common system used to identify the stage of CRC.34 It was developed by the American Joint Committee on Cancer (AJCC) and is reviewed and revised every 6 to 8 years.35
The system classifies the stage of the cancer based on:36
- T category: the size of the original tumor and the extent to which it has grown into the inner layers of the colon or rectal tissue.
- N category: whether cancer cells have spread to lymph nodes.
- M category: whether the cancer has spread to other areas of the body (metastasis).
Each category’s letter is attached to a number that indicates the size of the original tumor and the extent to which the cancer has spread.37 The TNM scores indicate the stage of the cancer.38
Primary Tumor (T)
Lymph Nodes (N)
Metastasis (M)
Patients with mCRC often receive a sequence of different treatments, with one given after another. Each sequence is referred to as a “line of therapy.” If one line of therapy stops working, often a different therapy may be effective:
“First-line” mCRC therapy is the first time a patient is treated for metastatic disease.
“Second-line” therapy is used as another treatment if the cancer progresses or reoccurs during or after first line therapy.
“Third-line” therapy follows second line if that fails to produce the desired benefit.

References
Risk Factors
A risk factor is anything that affects your chance of getting a disease.55 While the exact causes for colon cancer remain unknown,56 research has shown that the following risk factors increase the chances of developing this cancer:
Symptoms
Colorectal cancer rarely has symptoms in its early development,77 which is when the disease is most treatable, so it is important to get screened before symptoms appear.78
Once present, symptoms may include:79
- Change in bowel habits or the consistency in your stool
- Constipation or diarrhea
- Stools are narrower than usual
- Bowel does not empty completely
- Rectal bleeding or traces of blood in your stool
- Persistent abdominal discomfort, i.e. cramps, gas, bloating
- Unexpected weight loss
- Fatigue or weakness
- Nausea or vomiting
A number of other health conditions can cause these symptoms. Your doctor is in the best position to determine the source of your symptoms. Typically, cancer does not cause pain during early stages, so it is important to see a doctor if you experience any of these symptoms, even if you feel fine.80,81

CRC Fact Sheet
1) Colorectal cancer (CRC) is the third most common cancer in men and women.
2) The colon makes up the first 4 to 5 feet of the large intestine, and the rectum is the last 7 inches.82
3) Colorectal cancer typically develops from a polyp, a benign (non-cancerous) tumor or tissue growth, in the inner lining of the colon or rectum. There are different kinds of polyps and some can become malignant (cancer), which is why it is best to remove them.
4) Research demonstrates that familial history plays a role in up to 25 percent of patients diagnosed with colorectal cancer.83,84
5) More than 90 percent of people diagnosed with CRC are age 50 or older.85 Seventy-two is the average age at diagnosis.86
6) Colorectal cancer rarely has symptoms in its early stages, so getting preventative screenings annually is important for catching the cancer early, when it is most treatable.
7) Cancer cells can spread to nearby lymph nodes or other parts of the body by traveling through the blood or lymph vessels.87
8) Colorectal cancer commonly spreads to the lungs,88 liver89 and bone.90
9) Colorectal cancer has five stages, depending on the location and extent of the cancer. Treatments differ by stage.
10) If colon cancer is found, it is highly treatable in its early stages. If the cancer spreads into nearby lymph nodes, chemotherapy followed by surgery has been a highly successful combination treatment.
11) In the most difficult cases — when the cancer has metastasized to other organs, such as the liver or lungs — treatment can prolong life.91
Early Diagnosis is Key!
It’s important to know that CRC can be treated and, if caught early, even cured. Preventative screenings are critical to detect CRC because it typically does not have symptoms at its early, most curable, stages.92
Preventative Screenings
Anyone 50 years of age and older is at greatest risk of developing CRC93 and is strongly encouraged to get annual screenings. If polyps are detected during a screening, they can be removed and CRC can be prevented.94 If CRC has developed but is caught before it spreads beyond the inner wall of the colon or rectum, there is a strong chance of curing the disease. The danger is when cancer cells spread to the outer wall tissue and to other organs or body parts. Consistent screenings are likely to detect cancer or pre-cancer cells before this happens.

Testing for CRC
Common tests and procedures that ensure an accurate diagnosis for colorectal cancer include:
- Colonoscopy: This is the most common procedure, which is when a gastroenterologist examines the inner lining of the colon and rectum by inserting a colonoscope (thin, long tube with a light and camera) through the rectum.96 Through this procedure, the doctor can find any abnormalities and can gather samples of tissue or cells for biopsy and further testing.97
- Small polyps can be removed from the colon or rectum to be analyzed for cancer. This removal is called polypectomy.98
- Barium Enema: Using x-rays and dye to visualize the colon on a film. This allows your doctor to see and evaluate the appearance of your entire colon.99
- Virtual Colonoscopy: Using multiple CT images to create a picture of the inside of your colon. This is an alternative if you are unable to undergo an actual colonoscopy.100

Metastatic Colorectal Cancer – What it Means for You
If you are diagnosed with mCRC, a number of treatment options are available. Your doctor will be in the best position to identify the most effective treatment for your situation, but it is important for you to be informed of all the options in order to have a productive discussion with your doctor. Knowledge and understanding of your condition equips you to take an active role in choosing and managing your treatment.
You can start by viewing our Resources page.