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Advances in Colorectal Cancer Research

Colorectal cancer cells stained different colors, against a black background

Colorectal cells grown into organoids, stem cell-derived human 'mini-organs' that are used to study human development and disease.

Credit: Hubrecht Organoid Technology (HUB)

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat colorectal cancer. They are also looking at what factors influence screening behaviors, how to address disparities, and the rising rates of colorectal cancer in younger people.

This page highlights some of the latest colorectal cancer research, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and findings from recent studies.

Prevention and Early Detection

Screening can prevent colorectal cancer through detection of precancerous growths, or polyps, which can be removed before they become cancerous. It can also allow colorectal cancers to be detected early, before they cause symptoms and when treatment may be more effective.

Colorectal cancer screening tests. These include colonoscopy, sigmoidoscopy, stool-based tests to detect hidden blood (fecal immunochemical testing (FIT) or fecal occult blood testing (FOBT)), and virtual colonoscopy. (See Screening Tests to Detect Colorectal Cancer and Polyps for more information.)

Despite the availability of effective colorectal cancer screening tests, some people choose not to get screened. Some reasons may be because of the personal nature of the procedures, a lack of recommendation by their doctor, perceived costs or lack of insurance, or the preparation involved for a colonoscopy.

Although not currently recommended for screening, there are new techniques under development such as:

  • finding technologies that improve the genetic analysis of stool samples, which may reveal the presence of tumor DNA
  • looking at changes in the gut microbiome and trying to identify specific bacteria that could potentially help identify patients at risk for colorectal cancer

Repeat screening or follow-up. The guideline for getting a screening colonoscopy is every 10 years. However, people who have noncancerous polyps detected at colonoscopy are generally asked to return for a repeat colonoscopy earlier than that.

NCI’s FORTE Colorectal Cancer Prevention Trial, is now looking at whether some people with one or two small polyps can wait 10 years before returning for another colonoscopy. By comparing two study groups, one with repeat colonoscopy after 5 years, and one with repeat colonoscopy after 10 years, researchers hope to learn whether waiting 10 years is as good at preventing colorectal cancer as follow-up exams after 5 years. 

For colorectal cancer screening to be effective, people need to follow up on abnormal test results. In one study, researchers found that people who had a positive at-home stool test to screen for colorectal cancer, but did not have a follow-up colonoscopy, were twice as likely to die from colorectal cancer as those who did have a follow-up colonoscopy.

NCI is funding research to better understand the many factors that can contribute to why a person may not have a follow-up test and how to increase repeat screening and follow-up colonoscopy after abnormal stool tests. Researchers are also studying how the many levels of the healthcare delivery system affect the decision to get screened.

Treatment for Colorectal Cancer

Surgically removing the cancer is the most common treatment for many stages of colorectal cancer. Chemotherapy, radiation, targeted therapy, radiofrequency ablation, and cryosurgery are other treatments that may be used to treat colorectal cancer, depending on the stage.

Because of an increased risk of recurrence, differences in anatomy, and poorer prognosis, the treatment of rectal cancer may differ from that of colon cancer. Although surgery remains a common type of treatment for local and locally advanced rectal cancer, people with some stages may be treated with radiation, chemotherapy, and/or targeted therapy with or without surgery.

In addition to these standard treatments for rectal cancer, researchers continue to study both new treatments, such as immunotherapies, and new combinations of existing treatments in clinical trials.

One trial is comparing a standard treatment (chemoradiation followed by combination chemotherapy) with chemoradiation followed by combination chemotherapy that includes an additional chemotherapy drug. The goal is to find out whether the additional chemotherapy drug may increase the likelihood of the cancer responding and possibly avoid the need for surgery. 

Immunotherapy for patients with Lynch syndrome or MSI-H colorectal cancer

Approximately 5% of colorectal cancer cases are due to Lynch syndrome, an inherited DNA repair disorder. People with this disorder have an increased risk of developing colorectal cancer, typically before they reach the age of 50. Lynch syndrome colorectal cancer tumors have many mutations, which may make them more susceptible to immunotherapies.

A genetic feature known as microsatellite instability-high (MSI-H) is seen in about 15% of patients with stages II and III colorectal cancer and about 5% with stage IV. MSI-H means that there are mistakes in the way the DNA is copied in cancer cells, which can make them grow out of control.

The immune checkpoint inhibitors nivolumab (Opdivo), ipilimumab (Yervoy), and pembrolizumab (Keytruda) have all been approved for the treatment of metastatic colorectal cancer in patients with Lynch syndrome and in patients with MSI-H cancers. 

The NCI-sponsored COMMIT study is testing the addition of atezolizumab (Tecentriq) to the combination of chemotherapy and the targeted therapy bevacizumab (Avastin), for treating patients that have defective DNA mismatch repair. The hope is that combining drugs that work in different ways will improve treatment results in patients with colorectal cancer.

Another NCI-sponsored trial is studying whether atezolizumab will improve outcomes in people with earlier-stage disease (specifically, stage III colon cancer) that is deficient in DNA mismatch repair. This trial will compare combination chemotherapy with or without atezolizumab.

For people with locally advanced rectal cancer who have MSI-H cancer, one trial is studying the effects of nivolumab and ipilimumab when given together with short-course radiation therapy

Combining immunotherapy with other treatments for patients without Lynch syndrome

Immune checkpoint inhibitors have been less effective in colorectal cancer patients without Lynch syndrome and whose cancers don't have mismatch repair deficiency. Scientists are currently testing various agents, such as chemotherapy drugs, targeted therapies and viruses, in combination with immune-based therapy to determine whether combining treatments would be effective in killing cancer cells.

Using targeted therapies for metastatic colorectal cancer

Using targeted therapies against genetic mutations that may drive tumor growth is another key area of research for metastatic colorectal cancer. The goal is to find agents that can block the activity of the abnormal proteins produced by these mutations. For example:

Testing liquid biopsies

Liquid biopsies are a promising new approach being explored to detect, analyze, and track DNA, cells, and other substances shed from tumors into bodily fluids, such as blood and urine. Scientists are testing this method to detect colorectal cancer early, measure treatment responses, identify treatment resistance, and monitor for disease recurrence.

One example is the COBRA trial, which found that testing blood for fragments of genetic material (DNA) shed by tumors, known as circulating tumor DNA (ctDNA), could identify patients with stage IIA colon cancer who might benefit from additional treatment with chemotherapy after surgery.

An ongoing trial is studying ctDNA in people with stage II or III colon cancer. The goal is to determine whether and what type of chemotherapy will benefit patients who have had surgery for their colon cancer based on the presence or absence of ctDNA. 

NCI-Supported Research Programs

Many NCI-funded researchers at the NIH campus, and across the United States and world, are seeking ways to address colorectal cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts for colorectal cancer.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for colorectal cancer screening, to prevent colon and rectal cancer, and treatment for colon cancer and rectal cancer. 

Colorectal Cancer Research Results

The following are some of our latest news articles on colorectal cancer research:

View the full list of Colorectal Cancer Research Results and Study Updates.

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