The CLF is pleased to announce Leandro Cerchietti, MD, Assistant Professor, Weill Cornell Medical College, and Rachael Clark, MD, PhD, Associate Professor, Brigham and Women's Hospital Department of Dermatology as the recipients of the 2013 CLARIONS Research Award Grant.
Title of Research: Thyroid hormone receptor modulation in CTCL treatment
Below is an explanation of Dr. Cerchietti's proposed research as stated in his proposal:
The purpose of our studies is to find new cures for patients with cutaneous T cell lymphoma (CTCL) by improving the currently available treatment. In previous studies we discovered that CTCL depend on the function of a hormone for survival. We also found that this hormone, called thyroid hormone,feed CTCL cells by two different mechanisms. One of these mechanisms is located in the nucleus of every cell and the other is located at the outer surface of CTCL cells. Since thyroid hormone is necessary for normal life, we cannot simply take it away from the body. We discovered that is possible to inhibit the outer surface mechanism in CTCL cells without affecting the nuclear mechanism present in every cell. By doing so, we were able to kill CTCL cells without affecting other cells necessary for body’s normal function. One of the most useful drug treatments for CTCL, generically called “rexinoids”, decrease the amount of thyroid hormone in the body forcing physicians to prescribe thyroid hormone replacement therapy to avoid serious side effects. We believe that thyroid hormone replacement therapy could decrease the anti-lymphoma effect of “rexinoids”. In this proposal, we will determine if thyroid hormone interfere with the anti-lymphoma effect of “rexinoids” and also if, by inhibiting the thyroid hormone effect at the surface of CTCL cells that we discovered, we can increase the anti-lymphoma effect of “rexinoids”. If successful, our studies will allow doctors to count with an improved treatment for CTCL in the future.
Rachael Clark, MD, PhD
Title of Research Project: Low dose XRT as a cure for skin resident T cell lymphomas
Below is an explanation of Dr. Clark's proposed research as stated in her proposal:
Mycosis fungoides (MF) is a type of cutaneous T-cell lymphoma (CTCL) characterized by long-standing inflamed skin lesions containing a population of malignant T cells. Although several topical therapies can suppress the disease, none are curative. Clinically, we have found that two very low doses (4Gray) of irradiation therapy (XRT) can induce long standing improvement and a perhaps a cure of MF skin lesions. Because malignant T cells are only present within inflamed skin lesions in MF patients, a treatment that kills malignant T cells in skin has the potential to be a true cure. Identification of the malignant T cells in MF is difficult and it has never been possible to determine if a particular therapy actually kills malignant T cells or not. Using a new cutting edge technology called deep TCR gene sequencing, we have now been able to identify and quantify both the malignant and healthy T cells in MF skin lesions. We propose here to biopsy MF skin lesions before and after low-dose XRT and to determine if the malignant T cells are killed by this therapy. If so, low-dose XRT may be a true cure for MF. Also, we will study if the healthy T cells, which have been shown to fight off infection and protect against cancer, survive in these areas of
treated skin. If our initial clinical observations hold true, low-dose XRT may represent a true cure for MF that selectively kills malignant T cells while sparing normal immunity.