Article by Disease | New Medical Strategies for Midgut Carcinoids

Bentham Oncology Collection | Oncology | CARCINOID TUMOURS

Abstract:

Patients with well-differentiated neuroendocrine tumours of the gastrointestinal tract often present with metastases and hormonal symptoms. These patients can be palliated by interventional tumour reduction and medical treatment with somatostatin analogues; no effective chemotherapy is available. Radionuclide therapy via somatostatin receptors is one new therapeutic alternative. The recognition that neuroendocrine tumours express specific receptors for growth factors and chemokines, which are of importance for tumour growth, vascularization, and spread, may open the way for new therapeutic approaches. The signalling pathways in carcinoid tumours are incompletely explored. This review summarizes potential new treatment strategies from clinical and experimental studies, e.g. inhibition of angiogenesis, targeting of growth factors or their receptors by tyrosine kinase inhibitors, interference with specific cellular pathways (mTOR, PI3K, RAS/RAF, Notch), and also inhibition of the proteasome and histone deacetylation. Combining targeted therapy with chemotherapy, or using drugs to sensitize for radionuclide therapy, may enhance the treatment outcome.

 

Read out more at: http://www.eurekaselect.com/node/71224/article

Article by Disease | New Medical Strategies for Midgut Carcinoids

Bentham Oncology Collection | Oncology Carcinoid Tumours

 

Abstract:

Patients with well-differentiated neuroendocrine tumours of the gastrointestinal tract often present with metastases and hormonal symptoms. These patients can be palliated by interventional tumour reduction and medical treatment with somatostatin analogues; no effective chemotherapy is available. Radionuclide therapy via somatostatin receptors is one new therapeutic alternative. The recognition that neuroendocrine tumours express specific receptors for growth factors and chemokines, which are of importance for tumour growth, vascularization, and spread, may open the way for new therapeutic approaches. The signalling pathways in carcinoid tumours are incompletely explored. This review summarizes potential new treatment strategies from clinical and experimental studies, e.g. inhibition of angiogenesis, targeting of growth factors or their receptors by tyrosine kinase inhibitors, interference with specific cellular pathways (mTOR, PI3K, RAS/RAF, Notch), and also inhibition of the proteasome and histone deacetylation. Combining targeted therapy with chemotherapy, or using drugs to sensitize for radionuclide therapy, may enhance the treatment outcome.

 

Read out more at: http://www.eurekaselect.com/node/71224/article

 

OPEN ACCESS ARTICLE – Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

Journal Name: Mini-Reviews in Medicinal Chemistry

Author(s): Voon Yee-Lin*, Wong Pooi-Fong , Alan Khoo Soo-Beng

 

 

 

 

Graphical Abstract:

 

Abstract:

Nasopharyngeal carcinoma (NPC) is a form of head and neck cancer of multifactorial etiologies that is highly prevalent among men in the population of Southern China and Southeast Asia. NPC has claimed many thousands of lives worldwide; but the low awareness of NPC remains a hindrance in early diagnosis and prevention of the disease. NPC is highly responsive to radiotherapy and chemotherapy, but radiocurable NPC is still dependent on concurrent treatment of megavoltage radiotherapy with chemotherapy. Despite a significant reduction in loco-regional and distant metastases, radiotherapy alone has failed to provide a significant improvement in the overall survival rate of NPC, compared to chemotherapy. In addition, chemo-resistance persists as the major challenge in the management of metastatic NPC although the survival rate of advanced metastatic NPC has significantly improved with the administration of chemotherapy adjunctive to radiotherapy. In this regard, targeted molecular therapy could be explored for the discovery of alternative NPC therapies. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. This review discusses the potential use of Nutlin-3 as a p53-activating drug and the future directions of its clinical research for NPC treatment.

 

READ MORE HERE: http://www.eurekaselect.com/154246 

Highlighted Article – Nutlin-3, A P53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment – Mini-Reviews in Medicinal Chemistry

MRMC- Articles_17-18-Voon Yee-Lin

To access this article, please visit: http://www.eurekaselect.com/154246

 

Press Release for EurekAlert! Nutlin-3, a p53-Mdm2 antagonist for nasopharyngeal carcinoma treatment

This article by Dr. Voon Yee-Lin et al. is published in Mini-Reviews in Medicinal Chemistry, Volume 17, 2017

 

Nasopharyngeal carcinoma (NPC) is a common epithelial squamous cell head and neck cancer which is strongly associated with gamma herpes Epstein-Barr virus infection and the intake of salted fish. NPC incidence remain significantly high among men in the populations of Southern China, Hong Kong, Taiwan, Northern Africa and Southeast Asia. It has claimed many thousands of lives worldwide with approximately 80,000 new cases diagnosed annually and a mortality rate that exceeds 50,000. There are several approaches to fight NPC, which include surgery, radiation therapy and chemotherapy. NPC treatment remain one of the most intractable challenge for medicine. Radiation therapy alone has failed to provide a significant improvement in the overall survival rate of NPC, compared to chemotherapy. Radiocurable NPC is still dependent on concurrent treatment of megavoltage radiation with chemo drugs. Chemo-resistance persists as the major challenge in the management of patients diagnosed with metastatic NPC. In view of these challenges, it is understandable that scientists are trying to discover p53-based targeted therapy which could be applied as effective NPC therapies.

Recent discoveries have demonstrated that utilizing Nutlin-3 as a p53 activator is promising strategy for cancer management in the future. This review describes the potential use of newly discovered anticancer molecule Nutlin-3 and the future directions of its clinical research for NPC treatment. Nutlin-3 specifically targets p53-Mdm2 interaction and offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. In this regard, restoration of p53 tumor suppressor gene with Nutlin-3 could be explored for the discovery of alternative NPC therapies. However, further research is necessary before such new therapeutic strategies can be fully realized. New cancer therapeutic strategies, induce p53-dependent actions and currently ongoing clinical trials for drugs against human cancers have also been mentioned in the review. This study suggests that the development of effective cancer therapeutics is still in progress. Although Nutlin-3 is far from ready for its clinical use for NPC, it is still an attractive alternative drug that should be given attention and explored further, given the poor prognosis and limited treatment choices for NPC.

This article is open access and can be downloaded from: http://www.eurekaselect.com/154246

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