What is targeted therapy?
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Most patients with thyroid cancer have satisfactory outcomes with surgery and radioactive iodine (RAI) therapy, but for advanced patients who have recurred after surgery and are not sensitive to RAI therapy, or who have developed extensive metastases, the options are limited.
With the advent of “precision medicine,” targeted therapies offer new hope for them. Targeted therapies are treatments that target specific “targets” carried by tumor cells at the molecular level.
What is “targeted therapy”?
What is a “target”? If there is a mutation in our normal cells, it can lead to the production of specific proteins inside or on the surface of the cell that “direct” the cell to grow and multiply uncontrollably, forming a tumor. This is called the “driver gene” of the tumor, and these abnormal proteins are the “targets” of targeted therapy.
Normal cells often do not have these “targets,” so targeted therapies can hit cancer cells more precisely, usually without accidentally injuring normal cells, and with fewer toxic side effects. In contrast, conventional chemotherapy does not have this selectivity, so it tends to “kill a thousand, but hurt hundreds” and has more toxic side effects.
There are two main classes of targeted therapies: monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKI). The former recognizes the “target” on the surface of the tumor cell; the latter enters the cell and binds to the “target” inside, cutting off the signaling pathways necessary for tumor cell growth and preventing tumor growth, multiplication, and infiltration.
What are the targeted drugs for thyroid cancer?
There are a number of targeted drugs for thyroid cancer.
Research has shown that the RET, RAS, RAF, and VEGF genes are strongly associated with the development and progression of follicular thyroid cancer, laying the foundation for molecularly targeted therapy for thyroid cancer. In addition, papillary carcinoma is associated with the RAF gene and medullary carcinoma is associated with the RET gene.
In recent years, targeted therapies have become a hot topic in thyroid cancer, especially in progressive (advanced) differentiated thyroid cancer (DTC, which mainly includes papillary and follicular carcinomas and accounts for more than 90% of all cases). One of the more established drugs is the small molecule TKI class.
There are currently 4 TKI’s available in the US for advanced thyroid cancer, of which only one is available in China. These 4 drugs are described in a table below. It is important to note that all drugs are indicated only for patients with advanced, ineffective conventional therapy and rapidly progressive disease; for early-stage patients, surgery remains the preferred treatment.
| Table 1: 4 US-marketed targeted drugs | |||
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Sorafenib |
Levatinib |
Cabozantinib |
Vandetanib |
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VEGFR: vascular endothelial growth factor receptor; PDGFR: platelet growth factor receptor; Flt-3: human FMS-associated tyrosine kinase 3; Kit: stem cell growth factor receptor; MET: hepatocyte growth factor receptor; EGFR: human epidermal growth factor receptor.
Currently, these targeted agents have shown relatively good efficacy and safety compared to conventional chemotherapy. Their main targets include genes that are closely related to thyroid cancer such as RAF and RET. There are also the vascular endothelial growth factor receptor (VEGFR) and platelet growth factor receptor (PDGFR), which are mainly associated with tumor neovascularization or lymphatic vessels, and the drugs can inhibit tumor neovascularization or lymphatic vessel formation.
Tumors develop and progress with neovascularization, so genetic or other molecular marker testing prior to use is not currently recommended by US guidelines for such multi-targeted anti-angiogenic drugs.
With the development of domestic and international research, there will be more drug options for targeted therapy in thyroid cancer, bringing more hope to patients with advanced disease.
Co-written by Dr. Jiaqian Hu, Cancer Hospital of Fudan University