medicine & health
The Secret Correlation between Cancer and Genetics By Ryan Gomes Image by Ruslan Kalendar. [CC-BY-SA 4.0]
D
NA – the foundational component of sequences in our bodies that helps us live and be unique from one another. This important structure in every single living organism holds many secrets that tell us about our past ancestral generations and our futures as well. Scientists are constantly trying to uncover these secrets and discover new information that will help improve the quality of human life. Dr. Federico Innocenti is an associate professor in the Division of Pharmacotherapy and Experimental Therapeutics of the UNC Eshelman’s School of Pharmacy. He uncovers secrets of our DNA and genetics that will be able to help treat future patients suffering with cancer, particularly cancers in the gastrointestinal regions of the body. Throughout his research, Dr. Innocenti observed how certain sequences of DNA might influence survival rates from gastrointestinal tumors and how those sequences might affect how our bodies
Dr. Federico Innocenti
respond to chemotherapies. The particular chemotherapy in Dr. Innocenti’s lab is a widely known drug called irinotecan, or CPT-11. Irinotecan inhibits the topoisomerase, a crucial enzyme that is needed for DNA replication. Cancer cells progress and spread through the body via DNA replication. When inhibiting topoisomerase, DNA replication of cancer cells cannot proceed, therefore preventing further progress of the tumors. Irinotecan is used to treat many types of cancers within patients, including metastatic colorectal cancer, the second most lethal form. Although irinotecan has a reputation to be very efficient and beneficial, studies show that roughly more than 30% of cancer patients who have taken irinotecan to treat their cancer, experienced a worse state of health.⁴ This is largely due to the dosage of irinotecan that doctors prescribe for patients. A higher dosage than necessary for the patient can result in CPT-11-induced toxicity that can cause severe neutropenia. Neutropenia is a reduction in blood counts of neutrophils, a type of white blood cell that helps the body defend against pathogens. Initially, scientists theorized that the link between the amount of dosage and patient health was related to certain factors such as the demographics of the patient like their gender and age, but research has shown that data does not reflect this.⁴ In order to understand and gain more informa-
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tion about the correlation between the dosage of irinotecan and the patient’s health, Dr. Innocenti’s lab has looked into the genetic makeup of cancer patients. In order to look into this, the Innocenti lab investigated a certain gene inside the human body called the UGT1A1
Figure 1. This figure above shows how much Irinotecan is necessary in each genotype (the top) in order to get similar SN-38 results (the bottom). It is seen that a patient with *1/*1 genotype needs much more irinotecan dosage in order to maintain similar SN-38 levels compared to the other 2 genotypes. Reprinted with permission. © (2014) American Society of Clinical Oncology. All rights reserved.
