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Published On: Tue, Aug 20th, 2019

Moffitt research: Merkel cell carcinoma genomic analysis, Possible new treatment strategy for lung cancer

By NewsDesk  @infectiousdiseasenews

Merkel cell carcinoma genomic analysis

photo/ PDPics

Merkel cell carcinoma (MCC) is a rare, aggressive skin tumor that is diagnosed in approximately 2,000 people each year in the United States. Since MCC affects so few people, it is difficult to study the genetic factors that lead to its development and how those factors correlate with response to therapy. However, Moffitt Cancer Center researchers have developed the largest descriptive genomic analysis of MCC patients to date, in collaboration with Foundation Medicine and the Dana Farber Cancer Institute. Their analysis, published in Clinical Cancer Research, will provide important information to improve the care and treatment of MCC patients for many years to come.

Researchers are beginning to learn more about how MCC develops and its associated risk factors. Many patients with MCC have mutations within their DNA that are caused by UV radiation exposure, demonstrating that exposure to natural or artificial sunlight increases a person’s risk. Additionally, DNA and proteins from the virus Merkel cell polyomavirus (MCPyV) are present in many patients with MCC, and it is now accepted that MCPyV plays an important role in MCC development in some cases.

In the past, patients with MCC had few effective treatment options, resulting in a poor prognosis with a 5-year survival rate of only 20%. However, Todd Knepper, PharmD, assistant member of the Department of Individualized Cancer Management at Moffitt, says that MCC patients now have hope for improved outcomes. “Just a few years ago there were no FDA-approved treatments for patients with MCC, but recently the treatment paradigm for advanced MCC has shifted dramatically with immune checkpoint inhibitors demonstrating remarkable efficacy in this disease,” said Knepper. “Indeed, since 2017 several immune checkpoint inhibitors have been approved for the treatment of patients with MCC, and clinical data have demonstrated their ability to improve patient response rates and survival.”

Read more at Moffitt Cancer Center

Possible new treatment strategy for lung cancer

Lung cancer is the second most common cancer found in both men and women. It is estimated there will be roughly 228,000 new lung cancer cases this year, and nearly 30% of those patients will have mutations in the KRAS pathway. This type of mutation makes the cancer more aggressive and difficult to treat. Researchers at Moffitt Cancer Center are hoping to change that. In a new study published in Cancer Research, the team discovered a new treatment approach that may help this group of patients.

KRAS is a gene that regulates cell signaling in an “on” and “off” manner, leading to normal cell growth and division. Mutations that occur in the KRAS gene cause the protein to ignore any “off” signals that it receives, which results in unchecked cell growth. This is why researchers have been investigating areas in the KRAS pathway as possible therapeutic targets. For example, in melanoma, therapies that target the BRAF mutation, a protein in the KRAS pathway, have led to a positive patient response.

Moffitt researchers believe the MEK kinase, also found in the KRAS pathway, can be a possible target for lung cancer treatment. Through a series of drug screens, cell line and animal model experiments, they found that lung cancer cells treated with the MEK inhibitor trametinib in combination with the cytokines TNFα and IFNγ resulted in substantially more cell death than treating with a MEK inhibitor alone. TNFα was identified in the 1970s as Tumor Necrosis Factor but initial enthusiasm for using it in cancer treatment was quickly dampened by inflammatory response induced following TNFα administration, and the fact that most tumor cells resist killing by TNFα. In this study, the research team found that MEK inhibitors increase the number of receptors on the cell surface for TNFα to bind to, which leads to the delivery of a more potent and sustained cell death signal. IFNγ, a cytokine known to be crucial for anti-tumor immunity, further enhances the anti-tumor activity of MEK inhibitors and TNFα. Importantly, MEK inhibitors also considerably increases expression of TNFα and IFNγ target genes, which can lead to increase in anti-tumor immunity.

Read more at Moffitt Cancer Center

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