Dataset Information

Targeted Therapy of Papillary Thyroid Cancer: A Comprehensive Genomic Analysis.

ABSTRACT:

Background

A limited number of targeted therapy options exist for papillary thyroid cancer (PTC) to date. Based on genetic alterations reported by the "The Cancer Genome Atlas (TCGA)", we explored whether PTC shows alterations that may be targetable by drugs approved by the FDA for other solid cancers.

Methods

Databases of the National Cancer Institute and MyCancerGenome were screened to identify FDA-approved drugs for targeted therapy. Target genes were identified using Drugbank. Genetic alterations were classified into conferring drug sensitivity or resistance using MyCancerGenome, CiViC, TARGET, and OncoKB. Genomic data for PTC were extracted from TCGA and mined for alterations predicting drug response.

Results

A total of 129 FDA-approved drugs with 128 targetable genes were identified. One hundred ninety-six (70%) of 282 classic, 21 (25%) of 84 follicular, and all 30 tall-cell variant PTCs harbored druggable alterations: 259 occurred in 29, 39 in 19, and 31 in 2 targetable genes, respectively. The BRAF V600 mutation was seen in 68% of classic, 16% of follicular variant, and 93% of tall-cell variant PTCs. The RET gene fusion was seen in 8% of classic PTCs, NTRK1 and 3 gene fusions in 3%, and other alterations in <2% of classic variant PTCs. Ninety-nine of 128 (77%) FDA-approved targetable genes did not show any genetic alteration in PTC. Beside selective and non-selective BRAF-inhibitors, no other FDA-approved drug showed any frequent predicted drug sensitivity (<10%).

Conclusion

Treatment strategies need to focus on resistance mechanisms to BRAF inhibition and on genetic alteration-independent alternatives rather than on current targeted drugs.

SUBMITTER: Hescheler DA

PROVIDER: S-EPMC8498581 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPapillary thyroid cancer (PTC) is the most common endocrine malignancy worldwide. The treatment of PTC has attracted extensive attention and discussion from the public and scholars. However, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric and knowledge map analysis to reveal the dynamic scientific developments in the PTC therapy field.MethodsWe retrieved publications related to PTC therapy from the Web of Scientific Core Collection (WoSCC) on May 1, 2023. The bibliometric package in R software, VOSviewer and CiteSpace software were used to analyze countries/regions, institutions, journals, authors, references, and keywords. Then, we systematized and summarized the research landscape, global trends and hot topics of research.ResultsThis bibliometric analysis spanned from 2012 to 2022 and involved 18,501 authors affiliated with 3,426 institutions across 87 countries/regions, resulting in the publication of 3,954 papers in 860 academic journals. Notably, the number of publications and citations related to PTC therapy research has exhibited a steady increase over the past decade. China and the United States have emerged as leading contributors in terms of publication count, with the United States also being the most cited country. Furthermore, among the top 10 institutions with the highest number of published papers, half were located in China. Among the journals, Thyroid is ranked first in terms of total publications and citations. The most productive individual author was Miyauchi Akira. While previous research primarily focused on surgery and radioactive iodine therapy, the increasing emphasis on health awareness and advancements in medical technology have led to the emergence of active surveillance, thermal ablation, and genomic analysis as prominent areas of research.ConclusionIn conclusion, this comprehensive and quantitative bibliometric analysis elucidates the research trends and hotspots within PTC therapy, drawing from a substantial body of publications. This study provides valuable insights into the historical and current landscape of PTC therapy research while also offering guidance for future research directions. This study serves as a valuable resource for researchers and practitioners seeking new avenues of exploration in the field.