Most Read Articles
25 Aug 2015
At the Northern Pharmacists Convention cum 48th Malaysian Pharmaceutical Society Seminar 2015 held recently at Bayview Beach Hotel, Penang, Sanofi invited three distinguished speakers – Dr Khaw Chong Hui, Dr Lo Kang Shang Chit, and Professor Dr Karl-Josef Gundermann – to speak on the importance of renal protection in managing diabetic hypertension, the use of antihistamines in managing chronic urticaria (CU), and the role of essential phospholipids (EPL) in fatty liver diseases, respectively.
Roshini Claire Anthony, 07 Nov 2017

Women who are underweight, particularly in their late teens and mid-thirties, may be at risk for early menopause, a recent study found. 

16 Aug 2014

New drug applications approved by US FDA as of 15-30 Aug which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.

Audrey Abella, 20 Jan 2017
Diabetes was not a risk factor for total knee replacement (TKR) due to severe knee osteoarthritis, a Singapore study found.

Targeting MYC with JQ1 may help treat anaplastic thyroid cancer

Stephen Padilla
03 Aug 2017

Targeting of the MYC protein appears to be an effective approach against anaplastic thyroid cancer (ATC), for which treatment options are limited, according to a recent study.

“Effective treatment of human ATC has long been a challenge for clinical oncologists. Many approaches, including tyrosine kinase inhibitor–based targeting therapies, failed to improve the outcome of patients with ATC. One possible difficulty is the complexity and heterogeneity in the genetic abnormalities underlying ATC,” researchers said. [Anticancer Agents Med Chem 2012;12:87–93; Curr Opin Oncol 2013;25:44–49]

JQ1, a potent inhibitor that effectively disrupts the interaction of bromodomain and extraterminal domain (BET) proteins with acetylated histones on chromatin, significantly inhibited the proliferation of four ATC cell lines by suppressing MYC and elevating p21 and p27 to reduce phosphorylated Rb and delay cell cycle progression from the G0/G1 phase to the S phase. JQ1 weakens epithelial-mesenchymal transition signals, thereby blocking cell invasion. [J Clin Endocrinol Metab 2017;102:268-2280]

“The four human ATC cell lines used in the present studies harbour complex genetic alterations,” researchers said. “Remarkably, JQ1 treatment was effective in suppressing proliferation and reducing invasion of tumour cells in these four cell lines, albeit with minor quantitative differences in the extent of responses.” [J Clin Endocrinol Metab 2010;95:5338–5347]

Two representative xenograft studies further validated these cell-based analyses, in which JQ1 inhibited the size and rate of tumour growth by hampering p21-cyclin/cyclin-dependent kinase-Rb-E2F signaling.

“These results suggest that targeting chromatin regulators such as BET proteins with JQ1 in these ATC tumour cell lines is effective,” researchers said. “These findings raise the possibility that JQ1 and its next-generation analogues could be beneficial for ATC patients.”

Moreover, JQ1 has been shown to be effective in reducing tumour growth in several myeloid-derived tumours, including acute myeloid leukaemia and multiple myeloma and thyroid anaplastic tumours in mouse models. [Clin Cancer Res 2017;23:430–440; Oncotarget 2015;6:17698–17712; Blood 2012;120:2843–2852; Blood 2014;123:697–705]

“It is tempting to speculate that other oncogenic drivers … in addition to MYC may be inhibited at the transcriptional levels via epigenetic modifications of bromodomain proteins or other components of chromatin-remodeling complexes,” researchers noted. “Determining whether such antagonists can be developed for potential treatment of ATC awaits future studies.”

In the present study, researchers examined the effects of JQ1 on proliferation and invasion in cell line and xenograft tumours, and identified key regulators critical for JQ1-affected proliferation and invasion of tumour cells.

One of the most aggressive cancers in humans, ATC derives from complex and heterogeneous genetic changes that make effective treatment a major challenge. Patients with ATC rarely survive beyond 1 year even though well-differentiated thyroid cancer responds well to radioiodine therapy and usually has a favourable therapeutic response. [J Clin Invest 2016;126:1052–1066]

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Endocrinology - Malaysia digital copy today!
DOWNLOAD
Editor's Recommendations
Most Read Articles
25 Aug 2015
At the Northern Pharmacists Convention cum 48th Malaysian Pharmaceutical Society Seminar 2015 held recently at Bayview Beach Hotel, Penang, Sanofi invited three distinguished speakers – Dr Khaw Chong Hui, Dr Lo Kang Shang Chit, and Professor Dr Karl-Josef Gundermann – to speak on the importance of renal protection in managing diabetic hypertension, the use of antihistamines in managing chronic urticaria (CU), and the role of essential phospholipids (EPL) in fatty liver diseases, respectively.
Roshini Claire Anthony, 07 Nov 2017

Women who are underweight, particularly in their late teens and mid-thirties, may be at risk for early menopause, a recent study found. 

16 Aug 2014

New drug applications approved by US FDA as of 15-30 Aug which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.

Audrey Abella, 20 Jan 2017
Diabetes was not a risk factor for total knee replacement (TKR) due to severe knee osteoarthritis, a Singapore study found.