Study of Cutaneous T-cell Lymphoma Genomics Likely to Lead to Targeted Therapies Soon, Expert Says

Study of Cutaneous T-cell Lymphoma Genomics Likely to Lead to Targeted Therapies Soon, Expert Says
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Booming knowledge of how genomics contributes to cutaneous T-cell lymphoma is likely to lead the way to new, targeted treatments for this type of cancer in the near future, according to Pierluigi Porcu, a professor of hematology at The Ohio State University Comprehensive Cancer Center.

Dr. Porcu shared his view on the future of cutaneous T-cell lymphoma at the HemOnc Today Melanoma and Cutaneous Malignancies annual meeting, held March 18–19 in New York. The physician/scientist, part of the Cutaneous Lymphoma Program at Ohio State, spoke at length about the challenges that have prevented treatment progress, as well as the promising options available today.

Pierluigi Porcu
Dr. Pierluigi Porcu (Photo courtesy of Ohio State University)

“There have been obstacles and issues regarding the definition of how to best approach patients with cutaneous T-cell lymphoma,” Dr. Porcu said, according to a news release. “Historically, there was strong institutional bias about the best treatment approaches, as this is a disease that was managed by experts, and really there was not a lot of focus on evidence base.”

He spoke about the divide between dermatologists, who treated patients with early stage disease, and medical oncologists, who were seeing patients with advanced-stage disease, as a large contributor to a slow progress in the understanding of the cancer.

“In the absence of an integrated multimodality program, it was impossible for anyone to have a full view of the progression of the disease.”

During the past 10 years, five drugs have been approved for cutaneous T-cell lymphoma (CTCL), of which three belong to the class of histone deacetylase inhibitors. These treatments aim to stop the cancer from advancing to later stages, since poor outcomes often go hand-in-hand with disease progression.

Recently, a host of publications exploring the genomics of cutaneous T-cell lymphoma have appeared, identifying key mutations.

“There is an explosion of genomic data that is going to provide a lot of information on the mutation landscape of CTCL, and I would imagine over the next several years that is going to lead to the identification of targets for therapy,” Dr. Porcu said.

In addition to the multiple molecular targets he mentioned during his presentation, his own research has focused on ZEB1, a gene he believes controls inflammatory factors in the development of cutaneous T-cell lymphoma.

“We really think ZEB1 plays a key role in the upregulation of IL-15 in CTCL, and demethylating the promoter with a demethylating agent is a strategy that we are looking into,” he said.

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