Translational research bridges the gap between scientific discovery, technologic development and patient treatment. Identification of specific oncogenes and tumor suppressor genes involved in thyroid carcinogenesis had a tremendous impact on clinical approaches for diagnosis, treatment and management of patients with thyroid cancer. Currently, the genetic basis of thyroid cancer is studied at the scale of whole genome, and high-throughput sequencing analysis of genetic alterations in thyroid fine needle biopsy samples is becoming a routine diagnostic procedure. Also, next-generation sequencing platforms offer clinicians an opportunity to identify targetable oncogenic events in thyroid cancers, and to select the most appropriate therapeutic strategy.
Developing drugs to specifically inhibit oncogenes has been a major field of cancer research. Understanding the signal transduction pathways, and identifying the appropriate intracellular targets in thyroid cancer cells are critical for successful drug development. As an example, thyroid cancer cells with mutant BRAF are dependent upon ERK signaling for proliferation, and their growth is suppressed by MAPK/ERK kinase (MEK) inhibitors. In clinical trials, tyrosine kinase inhibitors showed promising results in patients with progressive, BRAF-positive papillary thyroid cancer refractory to radioactive iodine. However, there are numerous challenges in the application of targeted therapies in patients with aggressive thyroid cancer. In fact, the majority of patients with advanced thyroid cancers treated with targeted therapies ultimately develop resistance to treatment.
Multiple factors account for therapeutic failures. Tumor heterogeneity is one of the major problems limiting the efficacy of targeted therapies and compromising treatment outcomes. Studies demonstrate that the molecular profiles generated of biopsies from the primary tumor and a metastatic site might be significantly different. In addition, the molecular profile of different metastatic sites might be disparate. Thyroid cancer cells can also accumulate new molecular aberrations in response to the selection pressure from therapies.
The complexity of thyroid cancer cell biology underlies the difficulties for the implementation of novel treatment into the clinical practice. Despite a growing number of cancer drugs in development, the proportion of successful phase 3 clinical trials in oncology is the lowest among all therapeutic areas. Therefore, there is a clear need in pursuing research that will help build a better foundation for the development of novel therapies.
In this Research Topic we encourage submission of research papers focusing on novel ideas, new technologies, and innovative approaches, which will increase our understanding of thyroid carcinogenesis, and allow personalized therapy to be implemented in patients with thyroid cancer.
Relevant topics include, but are not limited to:
_ Molecular heterogeneity of thyroid cancer;
_ Thyroid cancer microenvironment and resistance to therapy;
_ Novel molecular targets;
_ Molecular diagnostic of thyroid cancer;
_ Laboratory correlates for targeted agents;
_ Immuno-oncology (immune checkpoints, immune response to therapy)
_ Metabolic reprogramming in thyroid cancer;
_ Emerging experimental models of thyroid cancer;
_ Radiation and thyroid cancer; and
_ Translational research in pediatric thyroid cancer.
This collection is the second volume of
Translational Research in Thyroid Cancer