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more cells (self-renew), acquire more mutations, and populate into even more CSCs, this process relentlessly drives tumor growth in an even more aggressive manner. Dr. Boman’s research focuses on understanding the unique properties of CSCs that distinguish them from normal targeted therapies that translate into new, more effective, even curative, treatment for advanced cancer patients.11
The Gene Editing Institute
The Gene Editing Institute (GEI) in the CTCR was founded at the Helen F. Graham Cancer Center in 2015 with several central missions. One mission is to carry out grant-funded, innovative translational research on the use of gene editing in cancer, with a central focus on elucidating the transformation pathways as well as developing innovative technological approaches for studying the cancer process. Another mission is to provide a biomedical resource facility for the synthesis, hands-on training, and dissemination of gene editing technologies to undergraduate institutions as well as to advanced research laboratories throughout the world.12 Leading the way in gene editing with CRISPR technology — the “breakthrough of the year” in 2015
— the Graham Cancer Center conducts ground-breaking genetic engineering research. Widely recognized as a Editing Institute works at the molecular level, led by world-renowned molecular biologist Eric B. Kmiec, PhD. The institute uses primary and model cell systems,
with a special focus on versatile genetic tools known as CRISPRs, to determine how gene editing activates or suppresses cancers. Scientists identify sections of DNA that cause disease and then use nucleases, sometimes called “molecular scissors,” to snip out the faulty DNA and delete, modify, or replace it with a strand
of normally functioning DNA. Dr. Kmiec’s trailblazing research on the gene-protein
Bruce Boman, MD, PhD (third from the left), Director of the Colorectal Cancer Translational Research Program, with his laboratory team.
advance the promise of gene editing in the
Present GEI projects include:
1) Lung Cancer
In the fall of 2016, the GEI was successful in knocking out the NRF2 gene in
lung cancer cells.13 This gene is partly responsible for establishing resistance to chemotherapy in lung patients, resulting in ineffective therapeutic regimens. NRF2 was disabled in lung cancer cells, which are known to develop resistance
to standard anticancer drugs such as cisplatin. The results were clear; tumor cells that contain a disrupted NRF2
to cisplatin. Thus, disruption of the
NRF2 gene in lung cancer cells leads to heightened sensitivity and lower doses
of chemotherapy required to achieve enhanced killing capacity. Animal studies combinatorial therapy using gene editing and cisplatin are completed. The goal of this combinatorial therapy is to reduce the amount of chemotherapy required to reach
the toxicity and the adverse effects often borne by a cancer patient due to the
levels of anticancer drug required, the goal is to help reduce the tumor burden and improve the quality of life during cancer treatment. GEI has a partnership with the National Center for Advanced Technologies (NCATs) on this project and is in continuing discussions with the FDA about preparing a clinical protocol in lung cancer. This is critical since lung cancer is responsible for 30% of cancer deaths in Delaware. The GEI anticipates having a clinical trial for patients before the FDA.
2) Melanoma
Melanoma is one of the most common cancers in Delaware.1 In September
2016, the GEI, in collaboration with the melanoma team at the Wistar Cancer Institute, began a clinical study to use gene editing to reignite the killing potential
of human T-cells as functional agents in the treatment of melanoma. A melanoma tumor is extracted from a patient and the patient’s own T-cells are extracted from the tumor mass. The T-cells are treated with a 5-CRISPR multiplex system,
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Del Med J | March/April 2021 | Vol. 93 | No. 2
