Researchers Identify Potential Reason behind Colorectal Cancer Resistance to Chemotherapy

Chemotherapy resistance is a major challenge in treating various types of cancer. This is why researchers from the Center for Genomics (CG) at Zewail City of Science and Technology, University of Sheffield and University of Sussex, led by Dr. Sherif El-Khamisy, Director of CG, came together to reveal the mystery of cancer cell resistance to the chemotherapy agent (Irinotecan), which is frequently used in colorectal and breast cancer treatment, and its response is lost in most cases due to early onset of drug resistance.  

“Most chemotherapies kill cancer cells by causing many breaks in the DNA. Consequently, cancer cells fight back by trying to fix the breaks, causing resistance to therapy,” said El-Khamisy, “If we can find a way to hijack cancer’s fix and repair toolkit and make it less efficient, then we can tip the scale in favor of cancer cell death instead of survival,” he explained.

The team started their research by generating colorectal cancer cell (CRC) models that resisted irinotecan. They discovered that a specific modification in a protein called histone that wraps the DNA made repair much faster in cancer cells, which resulted in therapy resistance. This unanticipated mechanism of resistance is not due to alterations in the genes but instead the way genes express themselves – i.e. an epigenetic change.

“The histone mark worked as a director of a movie that can choose to eliminate, slow down, or accelerate certain scenes or dialogues, thus altering the movie for better (i.e. cancer cell death) or worse (i.e. cancer cell survival),” explained El-Khamisy. By then the team was able to inhibit the activity of the enzymes that regulate this histone mark and thus reversing the resistance of cancer cells. The team published their study findings in a paper titled “Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan” in the journal of Nucleic Acids Research with an impact factor of 9.202, on October 26, 2016.


The research is a continuous effort of the Center for Genomics at Zewail City to improve personalized therapies and minimize mortality rates among cancer patients. This study is built on the team analyses of cancer associated genetic changes published last year in Nature Reviews Cancer.

The team, led by El-Khamisy, consisted of 9 scientists including second author Mohamed Ashour, a Ph.D. student at the Center for Genomics.

About Center for Genomics:

The Center for Genomics employs the latest cutting-edge research combining genetics, biochemistry, cellular and molecular biology, and whole animal approaches to understand genomic differences underpinning health and disease. The center is led by Prof El-Khamisy with over 2300 citations and an H-index of 23.

About Zewail City of Science and Technology:

Zewail City of Science and Technology is a non-profit organization. It is dedicated to advancing education, research, and economic development. The City is governed by the Supreme Advisory Board (Board of Trustees) which includes five Nobel Laureates, and with a special Law that grants its independence.

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