AUG 12, 2021 8:05 AM PDT

Promising Drug Target Identified for Deadly Ovarian Cancer

WRITTEN BY: Annie Lennon

Scientists at the University of Alabama at Birmingham have identified a gene called DOT1L for its role in progressing the severity of ovarian cancer. They also found that inhibiting DOT1L enzymes may offer a new therapeutic approach to the disease. The results were published in Oncogenesis.

Ovarian cancer is one of the most deadly forms of cancer. The five-year survival rate for patients with advanced forms of the disease is between 10 and 30%. While the condition can occur at any age, it is most common among women aged 50 to 60 years old. 

Earlier research has shown that a gene known as DOT1L is overexpressed in many cancer types. In the present research, scientists sought to see whether the gene has a role in ovarian cancer too, and whether it could be used as a drug target. 

To do so, they examined publically available datasets from patients with ovarian cancer. They found that levels of DOT1L mRNA were significantly higher in patient-derived samples of ovarian cancer than in control tissues. 

They also found that patients with ovarian tumors and high DOT1L expression had shorter progression-free survival (PFS) and overall survival (OS) than patients with low DOT1L expression. 

While patients with low DOT1L expression had a median PFS of 19 months and a median OS of 45.73 months, those with high DOT1L expression had an average PFS of 13.1 months and an OS of 39.87 months. 

Clinical trials have found that EPZ-5676, a DOT1L inhibitor, is effective in treating MLL-rearranged leukemia. The researchers thus conducted experiments to see how the drug interacted with ovarian cancer cells. 

They found that it was able to block ovarian cancer tumor growth both in cellular models and in a mouse xenograft model. 

Upon examination of their cell models, the researchers found that DOT1L inhibition reduced levels of essential biosynthetic metabolites in ovarian cancer cells. It also increased apoptotic cell death for ovarian cancer cells by upregulating genes involved in programmed cell death. In some cell line tested, DOT1L inhibitor additionally upregulated the expression of ligands for natural killer cells. 

"Our results suggest that DOT1L might be a pharmacologically tractable drug target for ovarian cancer therapy," said Romi Gupta, lead author of the study. "It will also be useful in combination with other immunotherapeutic agents to further enhance their effectiveness in treating ovarian cancer."

 

Sources: OncogenesisMayo ClinicScience Daily

About the Author
  • Annie Lennon is a writer whose work also appears in Medical News Today, Psych Central, Psychology Today, and other outlets. When she's not writing, she is COO of Xeurix, an HR startup that assesses jobfit from gamified workplace simulations.
You May Also Like
SEP 02, 2021
Immunology
Hobit Activates Cancer-Killing Immune Cells
SEP 02, 2021
Hobit Activates Cancer-Killing Immune Cells
Innate lymphoid cells, or ILCs, are specialized immune cells that are increasingly entering the research spotlight. Thes ...
OCT 09, 2021
Cell & Molecular Biology
The Anti-Cancer, Copper-Binding Compounds Found in Fish
OCT 09, 2021
The Anti-Cancer, Copper-Binding Compounds Found in Fish
In the world's waterways, fish are confronted with endless challenges. For example, they have to defend themselves from ...
NOV 01, 2021
Cancer
Gut Microbiota Promotes Resistance to Prostate Cancer Therapy
NOV 01, 2021
Gut Microbiota Promotes Resistance to Prostate Cancer Therapy
  The American Cancer Society estimates that nearly 250,000 men in the United States will be diagnosed with prostat ...
NOV 05, 2021
Cancer
The Labroots 2021 Cancer Research and Oncology Virtual Event Poster Winner
NOV 05, 2021
The Labroots 2021 Cancer Research and Oncology Virtual Event Poster Winner
Every year, Labroots hosts an exciting series of Virtual Events that focus on various scientific topics. These virtual m ...
NOV 22, 2021
Cancer
A New Treatment Option for Patients with Cancer in the Eye
NOV 22, 2021
A New Treatment Option for Patients with Cancer in the Eye
Uveal melanoma (UM) is a rare malignancy characterized by the formation of cancer cells in the tissues of the eye. UM be ...
JAN 03, 2022
Cancer
Heating Up the Immune Response: Turning Cold Tumors Hot
JAN 03, 2022
Heating Up the Immune Response: Turning Cold Tumors Hot
Immune checkpoints are present on the surface of immune cells throughout the body.  Under normal conditions, they r ...
Loading Comments...