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发表于 2014-2-21 10:25:16
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New hope in the fight against childhood cancer
By: Dr. Akira Nakagawara, MD, PhD
President, Chiba Cancer Center
20 二月 2014
摘要
Blog post announcing a breakthrough in the search for a new treatment for neuroblastoma, written by Dr. Akira Nakagawara, principal investigator for Help Fight Childhood Cancer
Today, thanks to advances in modern medicine, 80% of children diagnosed with cancer are cured. But the prognosis is not nearly as good for children with neuroblastoma, the most common form of cancer diagnosed in infants. Neuroblastoma is a tumor of peripheral nerve tissues that often starts in the adrenal glands and sympathetic ganglia of the neck, chest, or abdomen, and affects approximately one in 8,000 children in the United States and Japan.
More than half of neuroblastoma cases are classified as high risk, and only 30% of these children are cured – a rate that has not improved for two decades. New treatments are urgently needed for this dangerous disease.
Our research team at the Chiba Cancer Center in Japan has been working to develop a new treatment for neuroblastoma. With the help of volunteers participating in the IBM World Community Grid initiative, we have just discovered seven new drug candidates that could potentially be used in new medicines that fight childhood neuroblastoma. These drug candidates work by activating a self-destruct mechanism present in neuroblastoma cancer cells, killing them without affecting healthy cells.
Neuroblastoma cells have a receptor on their surfaces called TrkB. When molecules bind to the TrkB receptor and inhibit its function, a tumor suppressor gene called p53 is activated, causing the neuroblastoma cell to self-destruct in a process called apoptosis. Apoptosis is one of the body's natural processes, and ordinarily helps to eliminate damaged cells before they can form a tumor. However, the TrkB receptor in neuroblastoma suppresses this self-destruct function. A similar TrkB process is involved when many adult cancers, including breast, lung, pancreatic, prostate, and colon cancers, metastasize (i.e. spread beyond an initial site). This means our findings may have implications for treating adult cancers as well.
Our strategy was to search for small molecules that would bind to and inhibit the TrkB receptor on cancer cells. There were millions of potential molecules to examine, making it infeasible to synthesize and test each of them in the laboratory. Instead, we partnered with World Community Grid to create the Help Fight Childhood Cancer project, using computer-based modeling on a massive scale to conduct this search. With the help of over 200,000 volunteers around the world contributing their spare computing power, we screened three million molecules in just two years – a process that would have taken more than 55,000 years on a single computer – and identified seven promising drug candidates for further study.
After additional laboratory testing, we have discovered that the seven drug candidates are very effective at destroying neuroblastoma tumors in mice, even at very low dosages, with no immediately apparent side effects. These results have been published in the peer-reviewed journal Cancer Medicine, available online since January 2014.
Based on these very promising findings, we are now seeking a pharmaceutical partner to collaborate on the further development and testing needed to produce an approved medicine.
This breakthrough was made possible by the support of volunteers around the world who donated their computing power through World Community Grid. On behalf of our research team, I would like to thank World Community Grid volunteers from the bottom of my heart.
Akira Nakagawara, MD, PhD, President, Chiba Cancer Center
大意：
HFCC取得进展
由于现代医学的发展80%的儿童癌症都可以得到及时的诊断和治疗。但是神经母细胞瘤是个例外。超过半数的神经母细胞瘤是恶性的，而恶性肿瘤只有30%的治愈率（近20年没有任何改善）。
借助IBM的WCG平台，我们发现了7种新的潜在药物，可以在不影响正常细胞的前提下，消灭癌细胞。
神经母细胞瘤细胞表面有个TrkB受体，一旦有分子和该受体结合，癌细胞就会自毁。因为大多数癌细胞（例如：乳腺癌、肺癌、胰腺癌、前列腺癌、肠癌以及癌细胞扩散）都和TrkB受体有关，所以我们的药物不仅可以用于神经母细胞瘤治疗，也很有可能用于其他癌症治疗。
在其后的实验室测试中，我们发现这7中候选药物，只用很小的剂量就能杀死实验鼠体内的神经母细胞瘤，而且没有大都副作用。研究结果论文发表在2014年1月的《癌症药物》杂志上了。
据此研究结果，我们现在正在寻找合作制药厂商，进行后续的开发及测试。 |
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发表于 2013-11-17 21:35:37