Using Liquid Biopsy To Monitor Colorectal Cancer

by Dr. Rashmi Chaturvedi Upadhyay

What is colorectal cancer?

Colorectal cancer encompasses both cancers of the colon and the rectum. According to the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), it is the second most common cancer worldwide after lung cancer. Colon cancer and rectal cancers are often grouped together due to similarities in their invasiveness. The colon and the rectum belong to the digestive system of the body. Functionally, the colon reabsorbs large quantities of water and nutrients from undigested food products as they pass through it. The rectum is the end of the colon and stores the waste material of the digested food before being expelled from the body. In general, most colorectal cancers begin as a form of polyp – that is a kind of growth on the inner lining of the colon or the rectum. Some of these polyps can become cancerous over a period of years.  However, it must be noted that not all polyp-like growths are cancerous in nature. The chance of these polyps becoming cancerous depends largely upon the kind of the polyp. Doctors can distinguish between different types of polyps and have found that the kind known as adenomatous polyp has the highest tendency to develop into cancerous polyps.

The usual symptoms of colorectal cancer are:

• Diarrhea
• Constipation
• Blood in the stool
• Abdominal pain and bloating issues
• Fatigue
• Unexplained iron deficiency in men.

Various stages of colon cancer

Colorectal Cancer Risk Factors

There are several factors which can increase the risk of an individual for colorectal cancer. There are several lifestyle-related factors that have been linked to an increased chance of getting colorectal cancer:

• Being overweight or obese
• Physical inactivity
• Certain types of diets, especially if they include highly processed meat
• Smoking
• Alcohol use

In addition, there are certain medical conditions which can predispose an individual to develop colorectal cancer:

• A personal history of inflammatory bowel diseases
• A family history of colorectal cancer or adenomatous polyps
• Having an inherited syndrome, like Lynch Syndrome for example.

Challenges in colon cancer diagnosis and management

Science and medicine have made rapid advancements in the area of colorectal cancer detection and treatment. Today, colorectal cancers are very much treatable and most of the patients have been known to lead a very normal life after it has been treated. However, at the same time, disease monitoring for such patients is a huge challenge. Carcinoembryonic antigen (CEA) is a routinely used biomarker for the surveillance in colorectal cancer patients which has been shown to be at elevated levels in the event of colorectal cancer. However, it has proved to be not a very reliable marker.

How can liquid biopsy address current challenges?

In recent years, a blood-based liquid biopsy approach for monitoring colorectal cancer has emerged and is about to enter the clinic. Using a liquid biopsy approach, the pathology lab can extract tumor DNA from a blood sample, which can be used for monitoring the disease progression. Healthy individuals shed very low levels of circulating nucleic acids in their blood due to constant tissue renewal. This delicate balance is thrown off when a person has developed cancer and the amount of DNA that finds its way into the blood stream increases significantly, enough to be detectable by the latest laboratory and analysis techniques. Therefore, the liquid biopsy approach has become a promising new method for monitoring therapy response, disease progression and even relapse long before any other screening method would be able to detect that the cancer has relapsed.

Colon Cancer Genetics

With rising cancer incidences in India, including many colorectal cancers, it is crucial to continue to develop newer ways and methods to detect colorectal cancer early on, when treatment is more straightforward and more likely to be successful. Recent advances in genetics have allowed us to get an unprecedented glimpse of tumor biology and the genetic mutations that drive colorectal (and other) cancers. The gene mutations that are most significant for detecting colorectal cancer due to how frequently they occur (Jauhri, M et al, 2017) are:

• KRAS- 35.7%
• BRAF- 7.1%
• PIK3CA- 16.1%
• NRAS- 6.3%
• TP53- 39.3%
• APC-29.5%

In various studies conducted in a group of Indian colorectal patients, it has been found that there is significant evidence of KRAS and APC mutations co-existing in these patients. Many of these mutations could be detected using a liquid biopsy approach providing clues towards disease progression.

Strand’s colon cancer test portfolio and pipeline

Right now, Strand offers single gene testing as well as a 48-gene panel and a 152-gene panel test for colorectal cancer. A liquid biopsy approach to address the surveillance of colorectal cancer in treated patients and also to study the efficacy of the treatment regimen is under development and will be available to doctors and patients in the near future. Liquid biopsy offers key advantages over traditional solid tissue biopsies required for diagnosis and mutation detection, in particular, that it is a minimally invasive blood test. Liquid biopsy makes the analysis and the monitoring of the disease a lot easier as the need for the tissue biopsy gets eliminated completely. Remember, colorectal cancer is quite treatable and genetic analyses can guide the treatment involving traditional chemotherapy based routes and other routes such as radiation or targeted therapy.

Visit www.strandls.com/strand-liquid-biopsy for more information on Strand’s portfolio of liquid biopsy tests.

Reference

Jauhri, M., Bhatnagar, A., Gupta, S., BP, M., Minhas, S., Shokeen, Y., & Aggarwal, S. (2017). Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing–based cohort study. Tumor Biology, 39(2), 101042831769226. https://doi.org/10.1177/1010428317692265