Rozita Yarmand, PhD, assistant professor, Department of Endocrine Neoplasia and Hormonal Disorders-Research, The University of Texas MD Anderson Cancer Center, discusses unmet needs in medullary thyroid cancer.

In medullary thyroid cancer, there is an activating missense mutation in the RET tyrosine kinase receptor, Yarmand says. As such, RET is active in the neuroendocrine tissue that normally expresses this protein. This suggests that RET is a prognostic indicator and an oncogene in medullary thyroid cancer.

The current standard of care for this disease includes multikinase TKIs like cabozantinib (Cabometyx) and vandetanib (Caprelsa). However, patients only have partial responses to these drugs and develop resistance rather quickly. Yarmand concludes there is a need for a novel compound with less toxicity and more durable responses than the currently available TKIs.

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Addressing Unmet Needs in Medullary Thyroid Cancer

Rozita Yarmand, PhD, assistant professor, Department of Endocrine Neoplasia and Hormonal Disorders-Research, The University of Texas MD Anderson Cancer Center, discusses targeting ATF4 in medullary thyroid cancer.

In chromosome 22, there is a tumor suppressor gene called ATF4. In mouse models, loss of ATF4 caused C-cell hyperplasia, which is associated with RET oncogene mutations. If 1 copy of ATF4 is lost, hyperplasia can occur, says Yarmand.

Using this information, the next steps would be to induce ATF4, says Yarmand, as overexpression of ATF4 has been found to lead to cancer cell death.

Dr. Yarmand Discusses Targeting ATF4 in Thyroid Cancer

Rozita Yarmand, PhD, assistant professor, Department of Endocrine Neoplasia and Hormonal Disorders-Research, The University of Texas MD Anderson Cancer Center, discusses how ATF4 targets RET for degradation and is a candidate tumor suppressor gene in medullary thyroid cancer.

Researchers were interested in exploring the genomic abnormalities in medullary thyroid cancer. Through this analysis, it was determined that, in chromosome 22, there are tumor suppressor genes, one of which is called ATF4. Researchers also found that these tumors could have loss or decrease of level of this protein.

Additionally, patients with low expression of ATF4 have poor overall survival compared with patients of high levels of ATF4 expression. In exploring the mechanism of action of ATF4, it was found that overexpression of ATF4 leads to cancer cell death by degradation of protein, which is an oncogenic driver.

Rozita Yarmand, PhD

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Addressing Unmet Needs in Medullary Thyroid Cancer

Dr. Yarmand Discusses Targeting ATF4 in Thyroid Cancer

Rozita Yarmand on Tumor Suppressor Gene in Medullary Thyroid Cancer