Research in colorectal cancer

We are always learning more about cancer. Researchers and healthcare professionals use what they learn from research studies to develop better practices that will help prevent, find and treat colorectal cancer. They are also looking for ways to improve the quality of life of people with colorectal cancer.

The following is a selection of research showing promise for colorectal cancer. We’ve included information from PubMed, which is the research database of the National Library of Medicine. Each research article in PubMed has an identity number (called a PMID) that links to a brief overview (called an abstract). We have also included links to abstracts of the research presented at meetings of the American Society of Clinical Oncology (ASCO), which are held throughout the year. You can find information about ongoing clinical trials in Canada from CanadianCancerTrials.ca and ClinicalTrials.gov. Clinical trials are given an identifier called a national clinical trial (NCT) number. The NCT number links to information about the clinical trial.

Some substances or behaviours may prevent colorectal cancer or lower your risk of developing it. The following is noteworthy research into ways to prevent colorectal cancer or lower your risk. These methods are not yet recommended in standard clinical practice.

Acetylsalicylic acid (ASA, Aspirin, salicylate) and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin, Advil, Nuprin) and naproxen (Naprosyn, Aleve), are linked to a lower risk of developing colorectal cancer (Cancer Epidemiology, Biomarkers and Prevention, PMID 25613116; International Journal of Cancer, PMID 24599876). NSAIDS may also prevent people who had precancerous tumours from developing another precancerous condition or colorectal cancer (BMJ, PMID 27919915). More research is ongoing to further our understanding of the role that NSAIDs may play in preventing colorectal cancer (Cancer Epidemiology, PMID 27504605; PLoS One, PMID 29425227; Trials, PMID 28143522; Contemporary Clinical Trials, PMID 27777129).

Celecoxib (Celebrex) is an NSAID. One study found that it prevented adenomas from coming back in people who had been treated for adenomas that had a high risk of recurring (Journal of National Cancer Institute, PMID 27530656).

Sulindac (an NSAID), with or without erlotinib (Tarceva) or eflornithine, may help prevent colorectal cancer in people with familial adenomatous polyposis (FAP). Researchers are currently looking at these drugs in clinical trials (BMC Gastroenterology, PMID 27480131; JAMA, PMID 27002448; JAMA Oncology, PMID 29423501; ClinicalTrials.gov, NCT01349881, NCT01187901).

Statins are drugs that lower cholesterol levels in the body. Some research suggests that statins may lower the risk for colorectal cancer (Cancer Epidemiology, PMID 27750068). One study showed that statins may help lower the risk for colorectal cancer in people with inflammatory bowel disease (Clinical Gastroenterology and Hepatology, PMID 26905907).

High amounts of calcium and vitamin D from your diet or supplements may lower the risk of developing colorectal cancer (International Journal of Cancer, PMID 27466215; Journal of Cancer, PMID 26918035). Other studies found that taking calcium supplements, vitamin D supplements or both may lower the risk of developing adenomas in the colon and rectum (World Journal of Gastroenterology, PMID 27182169; International Journal of Cancer, PMID 25156950). But some research shows that taking supplements does not lower this risk (New England Journal of Medicine, PMID 26465985; JAMA Oncology, PMID 27978548).

Screening tests help find colorectal cancer before any signs or symptoms develop. When cancer is found and treated early, the chances of successful treatment are better. The following is noteworthy research into screening for colorectal cancer.

Receiving free fecal immunochemical test (FIT) kits along with information about colorectal screening leads to greater successes in finding colorectal cancer early (Cancer, PMID 27906448; Journal of Cancer Education, PMID 29177920). One study showed that mailed FIT tests increased the number of people screened for colorectal cancer (JAMA, PMID 28873161). Another study showed that an app that let people order their own screening test increased colorectal screening (Annals of Internal Medicine, PMID 29532054).

Stool DNA testing is a promising way to screen for colorectal cancer. It finds DNA markers in cells that are shed into the stool from precancerous adenomas and cancerous tumours in the colon. People may find the stool DNA test easier to do than other screening tests for colorectal cancer because a colonoscope isn’t inserted into the intestine and you don’t need to clear the intestine (called bowel preparation) or restrict your diet before the test. The stool DNA test may find some types of adenomas in the colon better than other stool tests used in colorectal cancer screening, such as the FIT and fecal occult blood test (FOBT). Researchers are studying stool DNA testing in clinical trials (Journal of Gastrointestinal Cancer, PMID 26922358; New England Journal of Medicine, PMID 24645800; World Journal of Gastrointestinal Oncology, PMID 27190584; Postgraduate Medicine, PMID 26753807; World Journal of Gastroenterology, PMID 28210082; Mayo Clinic Proceedings, PMID 28473037, PMID 26520415; Clinical Colorectal Cancer, PMID 26792032; American Journal of Gastroenterology, PMID 29016565, PMID 29016558; JAMA, PMID 28873161; Gut, PMID 27974550). The US approved the Cologuard stool DNA test as a screening test for colorectal cancer, but it hasn’t been approved for use in Canada yet.

Virtual colonoscopy (also called CT colonography) uses a CT scan to create images of the colon. It is less invasive and more comfortable than a regular colonoscopy because a colonoscope isn’t inserted into the intestine. Some drawbacks of this test are exposure to radiation, having to travel to centres that have the equipment and the fact that CT scans can’t find very small polyps. More research is needed to find out what role virtual colonoscopy may have in screening for colorectal cancer (Clinical Radiology, PMID 26145187; Journal of the National Comprehensive Cancer Network, PMID 26285241; Endoscopy, PMID 28107763).

Capsule endoscopy (also called PillCam colon endoscopy or capsule colonoscopy) may be used as a screening test for colorectal cancer. In this test, you swallow a tiny pill (capsule) containing a camera. The camera takes pictures as it moves through the digestive tract and is passed from the body. Doctors look at the pictures to see if there are any polyps or other abnormal areas in the colon or rectum. Your bowels need to be as empty as possible for capsule endoscopy. So one disadvantage of preparing for this test compared to preparing for a standard endoscopy is that you may need to take more laxatives closer to the time of the test. Capsule endoscopy does not seem to be as good as colonoscopy at finding polyps or abnormalities. Most research suggests that capsule endoscopy is best used after a positive stool screening test such as FOBT or FIT. It may also be a good alternative to regular colonoscopy in people who can’t have the procedure (Annals of Translational Medicine, PMID 27867950, PMID 28567375; Clinical Gastroenterology and Hepatology, PMID 27165469, PMID 26133904; Gastroenterology, PMID 25620668).

Blood tests for colorectal cancer screening are an alternative to screening with stool samples that you have to collect at home. These blood tests look for certain biomarkers in the blood. When there is a change in the amount of a biomarker, it may mean the person has cancer or a precancerous condition. A positive blood test result may suggest that you have a higher than average risk of developing colorectal cancer. SEPT9 is an example of blood tests that researchers are studying for colorectal cancer screening and diagnosis. When used with a stool test, such as FIT, SEPT9 seems to enhance screening. SEPT9 may also be effective in predicting prognosis and monitoring response to treatment, but more research is needed. SEPT9 and other blood tests to screen for colorectal cancer are starting to become available in Canada, but they aren’t currently part of provincial and territorial screening programs (Cancer Biomarkers, PMID 28128742; Clinical and Translational Gastroenterology, PMID 28102859).

Early screening for young cancer survivors who received radiation therapy to the abdomen or pelvis may help prevent colorectal cancer from developing. Cancer survivors who had radiation to the abdomen or pelvis have a higher risk for colorectal cancer. Clinical trial results show that these people should have early screening for colorectal cancer to prevent the disease (Gut, PMID 27411369).

A key area of research looks at better ways to diagnose and stage colorectal cancer. Researchers are also trying to find ways to help doctors predict a prognosis (the probability that the cancer can be successfully treated or that it will come back after treatment). The following is noteworthy research into diagnosis and prognosis.

Biomarkers are substances, such as proteins, genes or pieces of genetic material like DNA and RNA, that are found naturally in the body. They can be measured in body fluids like blood and urine or tissue that has been removed from the body. A gene mutation or a change in the normal amount of a biomarker can mean that a person has a certain type of cancer. Biomarkers can also help doctors predict the prognosis or response to treatment in people with colorectal cancer. Researchers are looking at the following biomarkers to see if they can help doctors diagnose, predict a prognosis for and find out which treatments will benefit a person with colorectal cancer:

• microRNA (Cancer Science, PMID 28859241; Biomedicine & Pharmacotherapy, PMID 27701052)
• circulating nucleosomes (Cancers, PMID 28075351)
• tumour endothelial markers (Disease Markers, PMID 27965519)
• mismatch repair deficiency (Science, PMID 28596308)
• RAS mutations (Annals of Oncology, PMID 28368441)
• serum LDH (British Journal of Cancer, PMID 28081548)
• MAPK signalling pathway (Annals of Oncology, PMID 29045529)
• BRAF mutation (European Journal of Cancer, PMID 28595137)

Gene-based tests find differences between normal genes and genes that are changed (mutated) in cancer cells. Microarray analysis is a type of gene-based test that allows researchers to look at many genes together to see which ones are turned on and which ones are turned off. Analyzing many genes at the same time to see which are turned on and which are turned off is called gene expression profiling. Researchers hope that developing more gene-based tests will help doctors identify the best treatments for certain cancers, including colorectal cancer. Gene-based tests may also help doctors tailor more treatments to each person’s cancer based on their unique genetic makeup (Journal of Hematology and Oncology, PMID 28179005; Cancer, PMID 29338072; Journal of Clinical Oncology, PMID 28486044; Journal of the National Cancer Institute, PMID 29370427).

Liquid biopsy is a test that looks for cancer cells (called circulating tumour cells or CTCs) or pieces of tumour DNA (called circulating tumour DNA) in the blood or other body fluids. Some research shows that testing the blood for cancer cells can help doctors predict a prognosis and determine the best treatment for people with metastatic colorectal cancer (Oncotarget, PMID 27852040; Gut, PMID 28790159).

Being physically active may improve prognosis. Researchers found that people who were physically active before and after a diagnosis of colorectal cancer had a lower risk of dying from the disease than those who aren’t physically active (Oncotarget, PMID 27437765). A phase 3 clinical trial is looking at the physical activity levels and disease-free survival of people who have been treated for stage 2 or stage 3 colon cancer. The trial is trying to find out how effective it is to give health education materials along with a physical activity program compared to only giving health education materials (Canadian Cancer Trials, NCT 00819208).

Researchers are looking for new ways to improve treatment for colorectal cancer. Advances in cancer treatment and new ways to manage the side effects from treatment have improved the outlook and quality of life for many people with cancer. The following is noteworthy research into treatment for colorectal cancer.

Laparoscopic surgery uses a thin, tube-like instrument with a light and a camera (called a laparoscope) to remove tissue or organs through small surgical incisions (cuts) in the body. Researchers want to find out if laparoscopic surgery to remove rectal cancer is a good alternative to surgery through a larger cut in the abdomen (called open surgery). Laparoscopic surgery is linked with less blood loss and shorter hospital stays compared to open surgery. So far results show that laparoscopic surgery is just as effective in removing the tumour and preventing recurrence as open surgery (International Journal of Colorectal Disease, PMID 26847617, PMID 26137968; JAMA, PMID 26441180, PMID 29067426; New England Journal of Medicine, PMID 25830422).

High-intensity focused ultrasound (HIFU) focuses ultrasound waves to create intense heat, which destroys tissue. Researchers are studying HIFU as an alternative to surgery for treating colorectal cancer that has spread to the liver (Trials, PMID 28166812).

The following chemotherapy drugs or combinations are being studied as treatments for colorectal cancer:

• etirinotecan pegol (Cancer Chemotherapy and Pharmacology, PMID 29043412)
• S-1 (Cancer Chemotherapy and Pharmacology, PMID 27933371; Annals of Oncology, PMID 28383633)
• TAS-102 (Lancet Oncology, PMID 28760399)
• temozolomide (Temodal) (British Journal of Cancer, PMID 28427088)
• tegafur-uracil (UFT) (Trials, PMID 28441966)
• azacitidine (Vidaza) and entinostat (Oncotarget, PMID 28186961)

Combining hepatic arterial infusion with systemic chemotherapy is effective in treating colorectal cancer that has spread to the liver and can’t be removed with surgery (unresectable) in clinical trials. Hepatic arterial infusion delivers chemotherapy directly to liver tumours through the main artery of the liver (called the hepatic artery) (Journal of Surgical Oncology, PMID 29165816).

Intra-operative chemotherapy gives chemotherapy during surgery. Researchers are studying it in clinical trials to treat colorectal cancer and liver metastases (Journal of Cancer Research and Clinical Oncology, PMID 28849265; International Journal of Surgery, PMID 28624558).

Preoperative chemotherapy gives chemotherapy before surgery. Researchers are studying it in clinical trials to see whether it is helpful before surgery to remove colorectal cancer that has spread to the liver (International Journal of Clinical Oncology, PMID 27752787).

Hyperthermic intraperitoneal chemotherapy (HIPEC) involves pumping chemotherapy drugs through a warming device and then into the peritoneal cavity. Researchers are studying HIPEC in clinical trials to treat advanced colorectal cancer because this disease commonly spreads to the peritoneum (Journal of Gastrointestinal Oncology, PMID 26941985; International Journal of Hyperthermia, PMID 28142288; ClinicalTrails.gov, NCT02965248, NCT02830139).

Immunotherapy boosts or helps the immune system find and destroy cancer cells. Researchers are studying the following types of immunotherapy for colorectal cancer.

Monoclonal antibodies are both a type of immunotherapy and a targeted therapy. They bind to specific antigens on cancer cells to help destroy them. Researchers are looking at using monoclonal antibodies alone and with other drugs to treat colorectal cancer.

• Ramucirumab (Cyramza) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). It is showing promise in clinical trials as a treatment for colorectal cancer (Annals of Oncology, PMID 27573561, PMID 27733377; European Journal of Cancer, PMID 28412590; Lancet Oncology, PMID 25877855).
• Labetuzumab govitecan is an antibody-drug conjugate that targets VEGF. Clinical trials show that it may be helpful in treating colorectal cancer (Journal of Clinical Oncology, PMID 28817371).
• MABp1 is a monoclonal antibody that targets interleukin and is showing promise as a treatment for colorectal cancer (Lancet Oncology, PMID 28094194).

Immune checkpoint inhibitors work by stopping cancer cells from affecting immune system cells in our bodies. The immune system normally stops itself from attacking healthy cells in the body by having some cells make specific proteins called checkpoints. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Immune checkpoint inhibitors are monoclonal antibodies that work by blocking checkpoint proteins so T cells (a type of white blood cell) can attack and kill cancer cells. Some immune checkpoint inhibitors that researchers are studying to treat colorectal cancers with high microsatellite instability (MSI-H) in clinical trials include:

• pembrolizumab (Keytruda) (PLoS One, PMID 29284010)
• nivolumab (Opdivo) (Lancet Oncology, PMID 28734759)

Cancer vaccines simulate the immune system to attack cancer cells that are present in the body. Researchers are studying vaccinia ankara-5T4 in clinical trials to see if can be used to treat colorectal cancer (JAMA Oncology, PMID 28880972).

Targeted therapy drugs target specific molecules (usually proteins) that cause cancer cells to grow. Some targeted therapy drugs that researchers are studying to treat colorectal cancer include:

• axitinib (Inlyta) (Cancer Investigation, PMID 28426267)
• fruquintinib (Journal of Hematology and Oncology, PMID 28103904)
• trastuzumab (Herceptin) and lapatinib (Tykerb) (Lancet Oncology, PMID 27108243)

Researchers are studying new ways of using radiation therapy to treat colorectal cancer.

Intra-operative radiation therapy (IORT) gives radiation therapy during surgery. It allows doctors to deliver higher doses of radiation to the cancer than conventional radiation therapy. Research shows that IORT helps control the growth of the cancer. It may improve survival in people with colorectal cancer that has spread to tissues or lymph nodes close to where the tumour started (called locally advanced cancer). It seems that IORT is most effective when the cancer can’t be completely removed by surgery or when there are positive surgical margins (Radiation Oncology, PMID 28077144; Journal of Surgical Oncology, PMID 24510523).

Radioembolization combines radiation therapy with embolization. It is also called selective internal radiation therapy. It gives radiation directly to tumours using tiny radioactive beads (called microspheres). Using a catheter, the beads are placed inside blood vessels that feed a tumour, delivering a high dose of radiation to the tumour and also blocking the supply of blood to the cancer cells. Researchers are studying radioembolization in clinical trials to treat liver metastases in people who can’t have surgery or whose colorectal cancer doesn’t respond to chemotherapy (European Radiology, PMID 27059858; Annals of Surgical Oncology, PMID 25323474; Journal of Cancer Research and Clinical Oncology, PMID 24318568; Current Treatment Options in Oncology, PMID 27098532; Lancet Oncology, PMID 28781171).

Radioimmunotherapy (RIT) combines radiation with monoclonal antibodies, a type of immunotherapy. Monoclonal antibodies specifically target cancer cells. When an RIT is injected into the body, the monoclonal antibody delivers the radioactive substance to the tumour (Cancer, PMID 27763687).

Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to tumours in fewer sessions than standard external radiation therapy. SBRT is delivered with many beams of radiation from different angles that meet at the tumour. The tumour itself receives a high dose of radiation, while the surrounding tissue receives a low dose. This lowers the effects of radiation on healthy tissue around the tumour. Clinical trials are looking at using SBRT to treat colorectal cancer that has spread to the liver (International Journal of Radiation Oncology, Biology, Physics, PMID 28871989)

Living with cancer can be challenging in many different ways. Supportive care can help people cope with cancer, its treatment and possible side effects. The following is noteworthy research into supportive care for colorectal cancer.

Mindfulness involves focusing on or being aware of your thoughts and emotions without judging them or believing there is a right or wrong way to feel. Several clinical trials have shown that mindfulness and meditation can be useful in relieving or reducing side effects of cancer as well as coping with many of the emotions that come with a cancer diagnosis, such as fear of recurrence (Cancer, PMID 28387949; Journal of Clinical Oncology, PMID 29095681).

Researchers continue to try to find out more about colorectal cancer. Clinical trials are research studies that test new ways to prevent, detect, treat or manage colorectal cancer. Clinical trials provide information about the safety and effectiveness of new approaches to see if they should become widely available. Most of the standard treatments for colorectal cancer were first shown to be effective through clinical trials.

Find out more about clinical trials.