Cancer of the Endocrine System

Lal, Geeta; O’Dorisio, Thomas M.; McDougall, Ross; Weigel, Ronald J.

doi:10.1016/b978-0-443-06694-8.50079-8

Cited by 9 publications

(8 citation statements)

References 299 publications

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“…Histologically, carcinoma comprises approximately 98% of all thyroid malignancies. Papillary carcinoma is the most common thyroid carcinoma (80%), followed by follicular carcinoma (10–15%), medullary carcinoma (5–10%), and anaplastic carcinoma (2–5%) . Surgery, postoperative radioactive iodine therapy, and TSH suppression by L‐thyroxine administration form the basis of the treatment of well differentiated thyroid cancers.…”

Section: Introductionmentioning

confidence: 99%

c‐Met‐mediated reactivation of PI3K/AKT signaling contributes to insensitivity of BRAF(V600E) mutant thyroid cancer to BRAF inhibition

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Yang

et al. 2015

Molecular Carcinogenesis

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BRAF (V600E) mutation is the most commonly detected genetic alteration in thyroid cancer. Unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response in thyroid cancer is reported to be low. The purpose of this study is to investigate the resistance mechanism responsible for this low treatment response to BRAF inhibitor in order to maximize the effect of targeted therapy. We examined the expression of feedback regulation mechanisms and alterations in the upper signal transduction pathway in thyroid cancer cell lines harboring BRAF mutation. Also, we investigated the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C (anaplastic thyroid cancer) and BCPAP (papillary thyroid cancer) were selected and treated with PLX4032 and its drug sensitivity were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on orthotopic xenograft mouse models. Unlike BCPAP cells, 8505C cells presented drug resistance to PLX4032 treatment and this was mainly due to increased expression of c-Met. Effective inhibitions of c-Met, p-AKT, and p-ERK were achieved after dual treatment with BRAF inhibitor (PLX4032) and c-Met inhibitor (PHA665752). Similar results were confirmed by in vivo study with orthotopic xenograft mouse model. c-Met-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF (V600E) mutant anaplastic thyroid cancer cells to PLX4032. Dual inhibition of BRAF and c-Met leads to sustained treatment response. © 2015 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

c‐Met‐mediated reactivation of PI3K/AKT signaling contributes to insensitivity of BRAF(V600E) mutant thyroid cancer to BRAF inhibition

Byeon

Yang

et al. 2015

Molecular Carcinogenesis

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“…TC is classified into major subtypes: differentiated (papillary [>85%], follicular [5–15%]), poorly differentiated (insular, solid, or trabecular), undifferentiated or anaplastic (1–2%), medullary (5%), and primary malignant lymphoma (2%) . Each histologic type of TC has its different and varied biologic behavior . TC incidence has increased almost 2.6‐fold from 1973 to 2006 .…”

Section: Discussionmentioning

confidence: 99%

“…MTC has a slightly female preponderance in a ratio of 1:1.05 . Although the role of the patient's age still remains controversial [,] the prognosis for MTC depends on the grade of cancer, extrathyroidal spread and size, as well as the quality of the initial surgical treatment . The overall prognosis rate is good, with a 5‐year survival of 78–91% and a 10‐year survival of 61–88% .…”

Section: Discussionmentioning

confidence: 99%

“…In some rare cases, the patient might present diarrhea either as a chief complaint or associated symptom, which has a higher incidence in patients with metastatic disease. Because the parafollicular cells are predominantly located in the upper portion of the thyroid lobe, most of the MTC are found in this area .…”

Section: Discussionmentioning

confidence: 99%

“…Medullary thyroid carcinoma (MTC) is an undifferentiated, neuroendocrine tumor which arises from the parafollicular cells or C‐cells of the thyroid gland. The particular characteristic of this tumor is the production of calcitonin as well as ACTH, histaminase, corticotrophin, vasoactive intestinal peptide, serotonin, and carcinoembriogenic antigen (CEA) . MTC can be either sporadic (SMTC) (65–70%) or familial (FMTC) as part of the multiple endocrine neoplasia type 2 (MEN2) syndrome .…”

Section: Introductionmentioning

confidence: 99%

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