New Agent May Offer Hope in Treating Thyroid Cancer

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The first-in-class compound CUDC-907 may be promising for anaplastic thyroid cancer and poorly differentiated thyroid cancer.
The first-in-class compound CUDC-907 may be promising for anaplastic thyroid cancer and poorly differentiated thyroid cancer.

An agent that is already in phase 2 testing for multiple myeloma and refractory lymphoma is now showing promise for thyroid cancer. Researchers from the National Institutes of Health (NIH) recently reported that they have found a drug that is versatile and may attack thyroid cancer in a novel way.

Investigators from the Endocrine Oncology Branch (EOB), which is part of the National Cancer Institute (NCI) at the NIH in Bethesda, Maryland, presented their latest findings with the first-in-class compound CUDC-907 at the 86th Annual Meeting of the American Thyroid Association (ATA). The compound inhibits both the PI3K signaling pathway and histone deacetylases (HDAC). These are believed to be 2 key regulators of cell growth, differentiation, and survival. They both have been implicated in thyroid cancer.

The researchers evaluated the antiproliferative effects of the drug in vitro in thyroid cancer cell lines. They also tested its effect in vivo on tumor growth and metastasis in a metastatic mouse model of thyroid cancer. The drug demonstrated significant anticancer activity.1 The researchers also demonstrated that CUDC-907 specifically reduces HDAC2 levels in thyroid cancer cells, which is preferentially overexpressed in anaplastic thyroid cancer and poorly differentiated thyroid cancer.1  

“These findings are clinically relevant because the data from the preclinical studies are very compelling. Currently, there are no active or standard therapies for anaplastic thyroid cancer and poorly differentiated thyroid cancer. These types of cancers account for a total of two-thirds of cancer-related deaths, and show overall poor survival outcomes,” said study investigator Shweta Kotian, ‎a postdoctoral fellow at the NCI.

Kotian, who presented the study findings at this meeting, said this agent has already demonstrated efficacy in phase 1 clinical trials for patients with multiple myeloma and patients with relapsed or refractory lymphoma.2 Kotian said the drug is in phase 2 trials currently for both patients with multiple myeloma and patients with refractory lymphoma.

So far, this agent appears to be safe and have acceptable tolerability.  The most common grade 3 or worse adverse events occurred in 43% of the patients in the phase 1 trial for multiple myeloma or refractory lymphoma.2 The most common side effects were thrombocytopenia, neutropenia, and hyperglycemia.2

In this current study, Kotian and colleagues found that CUDC-907 appears to induce differentiation of thyroid cancer cells by increasing mRNA expression of certain differentiation markers. This news is encouraging and suggests CUDC-907 could potentially be a new therapeutic agent worth pursuing in an attempt to combat thyroid cancer in a more targeted manner.

“The take-home message for endocrinologists is that this is a very promising therapeutic for thyroid cancer treatment. The EOB at the NCI is opening a phase 2 clinical trial for CUDC-907 next month for patients with locally advanced and metastatic thyroid cancers. We would like to invite endocrinologists to send their patients with such cancers for recruitment into the trial,” Kotian told Endocrinology Advisor.

Disclosures: Kotian reports no financial relationships or commercial interests.

References

  1. Kotian S, Zhang L, Boufraqech M, et al. Oral Abstract 18. Simultaneous inhibition of PI3K signaling and HDAC2 induces differentiation in thyroid cancer cells and suppresses tumorigenesis. Presented at: American Thyroid Association Annual Meeting; September 21-25, 2016; Denver, Colorado.
  2. Younes A, Berdeja JG, Patel MR, et al. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. Lancet. 2016;17(5):622-631. doi:10.1016/S1470-2045(15)00584-7.

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