Novel targeted therapies and immunotherapy for advanced thyroid cancers
Abstract Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15–20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, a...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-02-01
|
| Series: | Molecular Cancer |
| Online Access: | http://link.springer.com/article/10.1186/s12943-018-0786-0 |
| _version_ | 1817994156181553152 |
|---|---|
| author | George E. Naoum Michael Morkos Brian Kim Waleed Arafat |
| author_facet | George E. Naoum Michael Morkos Brian Kim Waleed Arafat |
| author_sort | George E. Naoum |
| collection | DOAJ |
| description | Abstract Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15–20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients’ overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor’s ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases. |
| first_indexed | 2024-04-14T01:49:11Z |
| format | Article |
| id | doaj.art-ec93a2aec25044b3ad7f175fc9b13cfe |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-14T01:49:11Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-ec93a2aec25044b3ad7f175fc9b13cfe2022-12-22T02:19:26ZengBMCMolecular Cancer1476-45982018-02-0117111510.1186/s12943-018-0786-0Novel targeted therapies and immunotherapy for advanced thyroid cancersGeorge E. Naoum0Michael Morkos1Brian Kim2Waleed Arafat3Department of Radiation Oncology, Harvard Medical School, Massachusetts General HospitalDepartment of Endocrinology, Rush UniversityDepartment of Endocrinology, Thyroid Cancer Program, Rush UniversityAlexandria Comprehensive Cancer centerAbstract Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15–20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients’ overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor’s ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.http://link.springer.com/article/10.1186/s12943-018-0786-0 |
| spellingShingle | George E. Naoum Michael Morkos Brian Kim Waleed Arafat Novel targeted therapies and immunotherapy for advanced thyroid cancers Molecular Cancer |
| title | Novel targeted therapies and immunotherapy for advanced thyroid cancers |
| title_full | Novel targeted therapies and immunotherapy for advanced thyroid cancers |
| title_fullStr | Novel targeted therapies and immunotherapy for advanced thyroid cancers |
| title_full_unstemmed | Novel targeted therapies and immunotherapy for advanced thyroid cancers |
| title_short | Novel targeted therapies and immunotherapy for advanced thyroid cancers |
| title_sort | novel targeted therapies and immunotherapy for advanced thyroid cancers |
| url | http://link.springer.com/article/10.1186/s12943-018-0786-0 |
| work_keys_str_mv | AT georgeenaoum noveltargetedtherapiesandimmunotherapyforadvancedthyroidcancers AT michaelmorkos noveltargetedtherapiesandimmunotherapyforadvancedthyroidcancers AT briankim noveltargetedtherapiesandimmunotherapyforadvancedthyroidcancers AT waleedarafat noveltargetedtherapiesandimmunotherapyforadvancedthyroidcancers |