Researchers Identify Role of ATP-Binding Cassette Transporters in Anaplastic Thyroid Cancer Resistance to Chemotherapy

ATP-binding cassette (ABC) transporters are the major determinants of anaplastic thyroid cancer (ATC) resistance to chemotherapy, and these transporters could be key in tailoring treatments for patients with ATC, according to a paper recently published in Endocrinology.

Researchers led by Vahid Haghpanah, MD, MPH, PhD, of the Endocrinology and Metabolism Research at the Tehran University of Medical Sciences in Tehran, Iran, point out that ATC has one of the worst prognoses of all types of cancer, because it’s so aggressive and resistant to treatment. “Current treatment approaches for ATC including surgery, external beam radiotherapy, and chemotherapy are not efficient and have not shown a considerable improvement in survival,” the authors write.

The researchers also write that the FDA recently approved a combination therapy with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for treatment of patients with unresectable or metastatic ATC with BRAFV600E mutation, leading to an overall response rate of 61% (95% CI, 39% to 80%). “This new treatment option for ATC highlights the importance of knowing the underlying mutation and mechanism of drug resistance in ATC” they write.

However, as the authors note, there are several mechanisms that limit the efficacy of current treatments for cancer – normal tissue toxicity and pharmacokinetic parameters of drugs restrict the recommended dosage of each drug and the amount of drug reaching cancer cells, for example.

But several studies have looked at defining the role of ABC transporters in ATC, since ABC transporters are involved in several physiological processes. Until now, there has been no systematic approach to assess the results of the previous studies. “Thus, this systematic review was designed to evaluate the possible roles of ABC transporters in ATC chemotherapy resistance.” The authors write.

The authors searched numerous databases, including Scopus, Web of Science, PubMed, Cochrane Library, Ovid, ProQuest, and EBSCO, for papers published since 1990, with predefined keywords. “In the eligible studies, the roles of 10 out of 49 ABC transporters were evaluated; among them, three pumps (ABCB1, ABCC1, and ABCG2) were the most studied transporters in ATC samples. ABCC1 and ABCG2 had the highest expression rates in ATC, and ABCB1 ranked second among the inspected transporters,” they write.

“In conclusion,” the authors write, “ABC transporters are the major determinants of ATC resistance to chemotherapy. By identifying these transporters, we can tailor the best treatment approach for patients with ATC. Additional studies are needed to define the exact role of each ABC transporter and other mechanisms in ATC drug resistance.”

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