Frequency and Clinical Impact of KRAS Mutations in Patients with Colorectal Cancer from the Middle East
Pages 67-74
Jamal Zekri, Syed Mustafa Karim, Ahmed Al-Shehri, Mervat Mahrous, Tarek Darwish and Hani El Taani

DOI: http://dx.doi.org//10.6000/1927-7229.2016.05.02.4
Published: 06 May 2016

Abstract:  Background: Colorectal cancer (CRC) is a significant healthcare burden worldwide and in the Middle East (ME). KRAS mutation confers resistance to epidermal growth factor receptor (EGFR) inhibitors in the treatment of advanced CRC. Data regarding the rate of KRAS mutation from the ME are scattered and scarce. We aim to collect and review all sizable studies evaluating the frequency of KRAS mutations in CRC patients from the ME.

Method: A Pubmed and Google Scholar search was conducted using keywords including KRAS, K-ras, colorectal cancer and Middle East, along with names of each ME country. Studies including over 90 patients were included in the review.

Result: Eleven studies containing more than 90 patients were identified. Among all eleven studies, KRAS mutation rate ranged from 13 to 56%. Five studies reported KRAS mutation rate in M1 stage either exclusively or as part of subgroup analysis. In these studies, mutations were found in 8-45% of cases. KRAS mutations were associated with female gender, M1 stage and high CEA in 3, 2, and 1 studies respectively.

Conclusion: There is a broad range of variability in KRAS mutation rate reported in different studies from the ME. This may have been due to small number of patients in the studies and lack of centralized testing for KRAS mutations. Larger and more coordinated studies from the ME population are required to ascertain the accuracy of KRAS mutation rate.

Emerging Therapeutics for Radioiodide-Refractory Thyroid Cancer
Pages 75-86
Juan Pablo Nicola and Ana María Masini-Repiso

DOI: http://dx.doi.org//10.6000/1927-7229.2016.05.02.5
Published: 06 May 2016

Abstract: Although uncommon, thyroid cancer constitutes the main endocrine neoplasia with an incidence rate that has been increasing steadily over the past decades. Recently, remarkable advances have occurred in understanding the biology of thyroid cancer. Novel germline and somatic point mutations as well as somatic chromosomal rearrangements associated with thyroid carcinogenesis have been discovered. Strikingly, acquired knowledge in the genetics of thyroid cancer has been translated into clinical practice, offering better diagnostic and prognostic accuracy and enabling the development of novel compounds for the treatment of advanced thyroid carcinomas.

Even after 70 years, radioiodide therapy remains as the central treatment for advanced or metastatic differentiated thyroid cancer. However, the mechanisms leading to reduced radioiodide accumulation in the tumor cell remain partially understood. Radioiodide-refractory thyroid cancer metastasis constitutes a central problem in the management of thyroid cancer patients. In recent years, the antiangiogenic tyrosine kinase inhibitors sorafenib and lenvatinib have been approved for the treatment of advanced radioiodide-refractory thyroid carcinoma. Moreover, still on clinical phase of study, oncogene-specific and oncogene-activated signaling inhibitors have shown promising effects in recovering radioiodide accumulation in radioiodide-refractory thyroid cancer metastasis. Further clinical trials of these therapeutic agents may soon change the management of thyroid cancer.

This review summarizes the latest advances in the understanding of the molecular basis of thyroid cancer, the mechanisms leading to reduced radioiodide accumulation in thyroid tumors and the results of clinical trials assessing emerging therapeutics for radioiodide-refractory thyroid carcinomas in the era of targeted therapies.