Fusion Transcript in Head and Neck Cancer

March 18, 2024

Head and neck cancer is a type of cancer that affects the mouth, nose, throat, larynx, sinuses, and salivary glands. It is the sixth most common cancer worldwide, with over 650,000 new cases diagnosed each year. Despite advances in treatment, the survival rate for head and neck cancer remains low, with a five-year survival rate of around 50%. However, a recent study by researchers at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbai, India, has identified a novel fusion transcript in head and neck cancer patients that could lead to new treatments for this disease.

What is a Fusion Transcript?

A fusion transcript is a type of genetic abnormality that occurs when two genes that are normally separate become fused together. This can happen as a result of a chromosomal translocation, where a piece of one chromosome breaks off and attaches to another chromosome. When this happens, the genes on the two chromosomes can become fused together, creating a new gene that has the characteristics of both original genes.
Fusion transcripts are important in cancer because they can lead to the production of abnormal proteins that drive the growth and spread of cancer cells. Many types of cancer, including leukemia, lymphoma, and sarcoma, are caused by fusion transcripts.

The UBE3C-LRP5 Fusion Transcript

The researchers at ACTREC identified a novel fusion transcript called UBE3C-LRP5 in head and neck cancer patients. This fusion transcript is the result of a chromosomal translocation between chromosomes 7 and 11. The researchers were able to map the translocation event to a single base pair resolution, which means they were able to identify the exact location of the breakpoint between the two chromosomes.
The UBE3C gene is involved in the ubiquitin-proteasome system, which is responsible for breaking down proteins in the cell. The LRP5 gene is involved in the Wnt signaling pathway, which is important for cell growth and development. When these two genes become fused together, it can lead to the production of an abnormal protein that drives the growth and spread of cancer cells.

Potential Treatment with Pyrvinium Pamoate

In addition to identifying the UBE3C-LRP5 fusion transcript, the researchers also found that an FDA-approved deworming drug called pyrvinium pamoate could be a potential treatment for head and neck cancer patients with this fusion transcript.
Pyrvinium pamoate is a drug that has been used for decades to treat parasitic worm infections in humans and animals. However, recent studies have shown that it also has anti-cancer properties. The drug works by inhibiting the Wnt signaling pathway, which is overactive in many types of cancer, including head and neck cancer.

The researchers at ACTREC tested pyrvinium pamoate on cancer cells with the UBE3C-LRP5 fusion transcript and found that it was effective at inhibiting the growth and spread of these cells. They also tested the drug on mice with head and neck tumors and found that it was effective at reducing tumor size and improving survival rates.

Implications for Precision Oncology

Precision oncology is an approach to cancer treatment that involves tailoring treatments to the specific genetic and molecular characteristics of each patient’s cancer. By identifying the specific genetic abnormalities that drive each patient’s cancer, doctors can select treatments that are more likely to be effective and have fewer side effects.

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