What’s New in Colorectal Cancer Research?

Research is always going on in the area of colorectal cancer. Scientists are looking for causes and ways to prevent colorectal cancer, better ways to find it early (when it's small and easier to treat), and ways to improve treatments. Here are some examples of current research. Treatment in a clinical trial is often the only way to get these treatments.

Reducing colorectal cancer risk

Many studies are looking to identify the causes of colorectal cancer. The hope is that this might lead to new ways to help prevent it.

Other studies are looking to see if certain types of diets, dietary supplements, or medicines can lower a person’s risk of colorectal cancer. For example, many studies have shown that aspirin and pain relievers like it might help lower the risk of colorectal cancer, but these drugs can have serious side effects. Researchers are now trying to figure out if the benefits might outweigh the risks for certain groups of people thought to be at high colorectal cancer risk.

Early detection

Doctors are looking for better ways to find colorectal cancer early by studying new types of screening tests (like blood tests) and improving the ones already being used. Researchers are also trying to figure out if there's any test or screening plan that clearly works best.

They're also looking for ways to educate and encourage people to get the routine screening tests that are available today and known to help reduce the number of deaths from this cancer.

Diagnosis

Researchers are trying to define colorectal cancer sub-types. This means grouping colorectal cancers based on things like the genetic mutations in the cancer cells, how the cells look and behave, how fast the cells are dividing, and features of the tumor itself. As has been found with other cancer types, this might lead to better understanding of disease progression and outcomes, as well as more clearly defined treatment plans (precision medicine).

Gene tests to help plan treatment

As doctors continue to learn more about the gene changes in colorectal cancer cells, certain gene tests have been developed to help predict which patients have a higher risk of colorectal cancer recurrence (the cancer coming back after treatment). These tests are being studied to see if they might help decide and if more treatment is needed after surgery and if they can predict outcomes.

Liquid biopsy to help plan treatment

Researchers are studying liquid biopsies for cancer diagnosis and treatment. A liquid biopsy is most often a sample of blood that is taken for cancer testing. It is much easier to get a sample of blood than it is to get a sample of the tumor with a needle. And studies have shown that liquid biopsies contain cancer cells as well as pieces of DNA from the cancer. Liquid biopsies might also be samples of urine, spinal fluid, or pleural effusions (fluid around the lungs).

Current research is testing colorectal cancer DNA from liquid biopsies to find specific gene mutations (changes). Researchers are hoping to find out if the gene changes could help doctors choose the best drugs for patients. Studies are also looking at if rising liquid biopsy tumor DNA levels predict that a cancer is no longer responding to certain drugs before an imaging test is done, or if it might predict the cancer is coming back after treatment (recurring).

Treatment

Researchers are always looking for better ways to treat colorectal cancer.

Surgery

Surgeons continue to improve the operations used for colorectal cancers. Rectal cancer surgery done through the anus, without cutting the skin, is also being studied.

Organ preservation -- keeping your body working the way it normally does -- is another research goal. For instance, doctors are looking at the ideal timing of surgery after chemo is used to shrink a rectal tumor and how to know when they've got the best response in each patient.

Sometimes when colorectal cancer recurs (comes back), it spreads to the peritoneum (the thin lining of the abdominal cavity and organs inside the abdomen). These cancers are often hard to treat. Surgeons have been studying a procedure called hyperthermic intraperitoneal chemotherapy (HIPEC). First, surgery is done to remove as much of the cancer in the belly as possible. Then, while still in the operating room, the abdominal cavity is bathed in heated chemotherapy drugs. This puts the chemo right in contact with the cancer cells, and the heat is thought to help the drugs work better. Some patients are living longer with this type of treatment, but more studies are needed to know which patients it can help. Doctors and nurses with special training and specialized equipment are also needed, so it's not widely available. 

For colorectal cancer that has spread to the liver and can’t be removed by surgery, another procedure being studied is hepatic arterial infusion chemotherapy (HAIC)  which often requires surgery. In this procedure, a pump or port (similar to a port for IV chemo but larger) is implanted close to the hepatic artery, which is the blood vessel feeding most cancers in the liver. The doctor can put chemo into the pump which is then released directly into the liver and helps kill the cancer cells while leaving healthy liver cells unharmed. Often, this procedure is given along with systemic chemo (chemotherapy given through a vein or CVC) to help tumors in the liver shrink more than if they had only gotten IV chemo, and hopefully make them able to be removed by surgery. More research is being done to find out which patients are the best candidates for this procedure. Currently it can only be done in facilities that are experienced.

Chemotherapy

Chemotherapy is an important part of treatment for many people with colorectal cancer, and doctors are constantly trying to make it more effective and safer. Different approaches are being tested in clinical trials, including:

  • Testing new chemo drugs or drugs that are already used against other cancers.
  • Looking for new ways to combine drugs already known to work against colorectal cancer to see if they work better together.
  • Studying the best ways to combine chemotherapy with radiation therapy, targeted therapies, and/or immunotherapy.

Better ways to identify, prevent, and treat chemo side effects are other areas of research interest.

Targeted therapy

Targeted therapy drugs work differently from standard chemotherapy drugs. They affect specific parts of cancer cells that make them different from normal cells. Several targeted therapy drugs are already used to treat advanced colorectal cancer. Researchers are studying the best way to give these drugs and looking for new targeted therapy drugs. Some new targeted drugs being studied are described below:

Most colorectal cancers that have spread are tested for common gene mutations in the KRAS, NRAS, and BRAF genes. If there are no mutations, then certain targeted drugs might be treatment options. If a colorectal cancer has a specific mutation in the BRAF gene, called BRAF V600E, then the targeted drugs cetuximab and panitumimab might be helpful if given along with targeted drugs called BRAF inhibitors and MEK inhibitors. These inhibitors are approved to treat some melanoma skin cancers, non-small cell lung cancers, and a few others. Cancers that have the BRAF V600E mutation make up about 5-10% of colorectal cancers and often have a poor prognosis (outcome). More studies are being done to find out the best combination of drugs for cancers with this mutation.

Some colorectal cancers that don’t have mutations in the KRAS, NRAS or BRAF genes, might make too much of the HER2 protein or HER2 gene. For these cancers, treatment with the targeted drugs trastuzumab and lapatinib or trastuzumab or pertuzumab might be an option. These drugs are approved for treatment in breast cancer and a few other cancers, but more research is needed for its use in people with colorectal cancer.

If a colorectal cancer doesn't have mutations in the KRAS, NRAS or BRAF genes, it might be tested for changes in one of the NTRK genes. These gene changes can lead to abnormal cell growth and cancer. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are targeted drugs that disable the proteins made by the abnormal NTRK genes. The number of colorectal cancers that have this mutation is very small (less than 1%) but this may be an option for some people.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Bray C, Bell LN, Liang H, Collins D, Yale SH. Colorectal Cancer Screening. WMJ. 2017;116(1):27-33.

Datta J, Narayan RR, Kemeny NE, D’Angelica MI. Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review. JAMA Surg. 2019;154(8):768–776. doi:10.1001/jamasurg.2019.1694.

Ko YJ, Karanicolas PJ. Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era. Curr Oncol. 2014;21(1):e116–e121. doi:10.3747/co.21.1592.

Mahasneh A, Al-Shaheri F, Jamal E. Molecular biomarkers for an early diagnosis, effective treatment and prognosis of colorectal cancer: Current updates. Exp Mol Pathol. 2017;102(3):475-483.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf on Feb 23, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf on Feb 23, 2020.

Osumi H, Shinozaki E, Yamaguchi K, Zembutsu H. Clinical utility of circulating tumor DNA for colorectal cancer. Cancer Sci. 2019;110(4):1148‐1155. doi:10.1111/cas.13972.

Roseweir AK, McMillan DC, Horgan PG, Edwards J. Colorectal cancer subtypes: Translation to routine clinical pathology. Cancer Treatment Reviews. 2017; 57:1-7.

São Julião GP, Habr-Gama A, Vailati BB, et al. New Strategies in Rectal Cancer. Surg Clin North Am. 2017;97(3):587-604.

Wright M, Beaty JS, Ternent CA. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97(3):683-701.

Yang YC, Wang D, Jin L, et al. Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients. Biosci Rep. 2018;38(4):BSR20180322. Published 2018 Jul 31. doi:10.1042/BSR20180322.

 

References

Bray C, Bell LN, Liang H, Collins D, Yale SH. Colorectal Cancer Screening. WMJ. 2017;116(1):27-33.

Datta J, Narayan RR, Kemeny NE, D’Angelica MI. Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review. JAMA Surg. 2019;154(8):768–776. doi:10.1001/jamasurg.2019.1694.

Ko YJ, Karanicolas PJ. Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era. Curr Oncol. 2014;21(1):e116–e121. doi:10.3747/co.21.1592.

Mahasneh A, Al-Shaheri F, Jamal E. Molecular biomarkers for an early diagnosis, effective treatment and prognosis of colorectal cancer: Current updates. Exp Mol Pathol. 2017;102(3):475-483.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf on Feb 23, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf on Feb 23, 2020.

Osumi H, Shinozaki E, Yamaguchi K, Zembutsu H. Clinical utility of circulating tumor DNA for colorectal cancer. Cancer Sci. 2019;110(4):1148‐1155. doi:10.1111/cas.13972.

Roseweir AK, McMillan DC, Horgan PG, Edwards J. Colorectal cancer subtypes: Translation to routine clinical pathology. Cancer Treatment Reviews. 2017; 57:1-7.

São Julião GP, Habr-Gama A, Vailati BB, et al. New Strategies in Rectal Cancer. Surg Clin North Am. 2017;97(3):587-604.

Wright M, Beaty JS, Ternent CA. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97(3):683-701.

Yang YC, Wang D, Jin L, et al. Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients. Biosci Rep. 2018;38(4):BSR20180322. Published 2018 Jul 31. doi:10.1042/BSR20180322.

 

Last Revised: June 29, 2020

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.