Abstract
The introduction of ultra-precision targeted therapy has become a significant advancement in cancer therapeutics by creating treatments with less off target effects. Specifically with papillary thyroid carcinoma (PTC), the cancer's hallmark genetic mutation BRAFV600E can be targeted with selective inhibitors, such as vemurafenib. Despite initial positive tumor responses of regression and decreased viability, both single agent or combination agent drug treatments provide a selective pressure for drug resistant evolving clones within the overall heterogeneous tumor. Also, there are evidences suggesting that sequential monotherapy is ineffective and selects for resistant and ultimately lethal tumor clones. Reconstructing both clonal and subclonal thyroid tumor heterogeneous cell clusters for somatic mutations and epigenetic profile, copy number variation, cytogenetic alterations, and non-coding RNA expression becomes increasingly critical as different clonal enrichments implicate how the tumor may respond to drug treatment and dictate its invasive, metastatic, and progressive abilities, and predict prognosis. Therefore, development of novel preclinical and clinical empirical models supported by mathematical assessment will be the tools required for estimating the parameters of clonal and subclonal evolution, and unraveling the dormant vs. non-dormant state of thyroid cancer. In sum, novel experimental models performing the reconstruction both pre- and post-drug treatment of the thyroid tumor will enhance our understanding of clonal and sub-clonal reconstruction and tumor evolution exposed to treatments during ultra-precision targeted therapies. This approach will improve drug development strategies in thyroid oncology and identification of disease-specific biomarkers.
Highlights
Specialty section: This article was submitted to Thyroid Endocrinology, a section of the journal Frontiers in Endocrinology
With papillary thyroid carcinoma (PTC), the cancer’s hallmark genetic mutation BRAFV600E can be targeted with selective inhibitors, such as vemurafenib
There are evidences suggesting that sequential monotherapy is ineffective and selects for resistant and lethal tumor clones. Reconstructing both clonal and subclonal thyroid tumor heterogeneous cell clusters for somatic mutations and epigenetic profile, copy number variation, cytogenetic alterations, and non-coding RNA expression becomes increasingly critical as different clonal enrichments implicate how the tumor may respond to drug treatment and dictate its invasive, metastatic, and progressive abilities, and predict prognosis
Summary
Specialty section: This article was submitted to Thyroid Endocrinology, a section of the journal Frontiers in Endocrinology. With papillary thyroid carcinoma (PTC), the cancer’s hallmark genetic mutation BRAFV600E can be targeted with selective inhibitors, such as vemurafenib.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
