Colorectal cancer (CRC) originates in the colon or rectum from abnormal versions of the epithelial cells that line the large intestine. Most of these cancers are adenocarcinomas, meaning they begin in mucus-producing glandular tissue. The disease often starts as a non-cancerous growth called a polyp, which develops on the inner wall of the colon or rectum. Over several years, cells within a polyp can undergo genetic changes that transform them into malignant cancer cells.
These initial growths can develop silently without causing noticeable symptoms, allowing a tumor to grow for a significant time before it is discovered. This article explores how these cells form, their characteristics, and the treatments used to combat them.
How CRC Cells Form
The transformation of a healthy colon cell into a CRC cell is a multi-step process driven by genetic mutations, often called the adenoma-carcinoma sequence. This begins when normal epithelial cells accumulate DNA changes in genes that regulate cell growth. One of the earliest mutations affects the APC gene, a tumor suppressor that helps control cell growth. When APC is inactivated, it leads to excessive cell proliferation and the formation of a small, benign polyp.
As cells in the polyp divide, they can acquire additional mutations. A mutation in the KRAS gene, for example, can cause the polyp to grow larger and more abnormal by leaving cell division signals permanently switched on. Subsequent mutations often involve tumor suppressor genes like TP53, which normally detects DNA damage. When TP53 is non-functional, it allows genetically damaged cells to survive and multiply, accelerating the transition from a benign adenoma to a malignant carcinoma.
Several factors can increase the likelihood of these genetic changes. Lifestyle and environmental influences are significant risk factors and include:
- Diets high in red and processed meats
- Obesity
- Smoking
- A lack of physical activity
Chronic inflammation from conditions like ulcerative colitis or Crohn’s disease also promotes cancer development by causing high rates of cell turnover. Additionally, some individuals inherit genetic predispositions, such as Lynch syndrome or FAP, which involve mutations that significantly increase their lifetime risk of developing CRC.
Detecting CRC Cells
Identifying CRC cells before they cause symptoms is a primary goal of screening. The most direct method is a colonoscopy, which allows a physician to visually inspect the entire colon and rectum using a flexible, camera-equipped tube. During this procedure, any suspicious growths or polyps can be removed and sent to a laboratory for analysis. A sigmoidoscopy is similar but examines only the rectum and lower part of the colon.
In the lab, a pathologist examines the removed tissue under a microscope in a process called a biopsy. This examination confirms whether cancer cells are present and provides information about the cancer’s grade, which describes how abnormal the cells look.
Non-invasive screening methods are also widely used to detect potential signs of CRC. Stool-based tests, such as the fecal immunochemical test (FIT), work by detecting tiny amounts of blood in the stool shed by polyps or tumors. Another type of stool test looks for altered DNA from cancer cells. If these tests produce a positive result, a colonoscopy is recommended to investigate the source.
CRC Cell Characteristics and Spread
CRC cells possess distinct biological traits that allow them to outcompete normal cells. A primary characteristic is their uncontrolled proliferation, which stems from mutations that disable the normal checks and balances of the cell cycle, allowing them to divide relentlessly and form a tumor. These cancer cells also evade apoptosis, or programmed cell death, a natural process the body uses to eliminate damaged cells. By ignoring these self-destruct signals, CRC cells can survive and accumulate further mutations.
This accumulation of genetic errors leads to genomic instability, where the rate of mutations accelerates and fuels the cancer’s evolution. This allows for local invasion, where cancer cells push through the colon wall into adjacent tissues, aided by enzymes that break down the surrounding matrix.
The most advanced capability of CRC cells is metastasis, the process of spreading to distant parts of the body. To achieve this, cells detach from the primary tumor and penetrate blood vessels or lymphatic channels to travel to other organs, most commonly the liver and lungs. Upon arriving at a new location, the cells invade the new tissue and begin to grow, forming a secondary tumor.
How Treatments Combat CRC Cells
Modern cancer treatments are designed to target the specific behaviors of CRC cells. Chemotherapy is a long-standing treatment that works by interfering with cell division. Because cancer cells divide much more rapidly than most normal cells, they are more susceptible to drugs that damage DNA or disrupt the machinery required for replication. This systemic approach affects cancerous cells throughout the body.
Targeted therapy represents a more precise strategy, using drugs designed to block specific molecules that CRC cells depend on for survival. For example, some colorectal cancers have an overactive EGFR protein on their surface that signals them to grow, and EGFR inhibitors can block this signal. Another approach is to use angiogenesis inhibitors, which prevent tumors from forming new blood vessels, thereby cutting off their supply of oxygen and nutrients.
Immunotherapy harnesses the power of the patient’s own immune system to fight the cancer. Some CRC cells have proteins on their surface that allow them to hide from immune cells. Drugs known as checkpoint inhibitors can block these proteins, “unmasking” the cancer cells and allowing the immune system to recognize and attack them. This approach has shown promise in CRC tumors that have a high number of genetic mutations.