Scientists develop a two-step approach to starve lung tumor cells
                     Source: Xinhua | 2018-04-03 04:39:00 | Editor: huaxia

    These two lung samples are from mice prone to develop Kras-mutant non-small-cell lung cancer. The lungs of mouse on the left are filled with tumors, as expected. The lung on the right, whose Kras-mutant cells have lost the Irs1/Irs2 genes, lacks the insulin/IGF-1 signaling needed for growth and is virtually devoid of tumors. (In a later stage, the tumors develop a workaround that enables them to start growing again.) (Credit: Clare (He) Xu, PhD, Boston Children's Hospital)

    WASHINGTON, April 2 (Xinhua) -- American scientists developed a two-prolonged therapy with a combination of drugs that are already available clinically to starve the tumor cells to death.

    The Boston Children's Hospital study, published on Monday in the Proceedings of the National Academy of Sciences, has shown that the non-small-cell lung cancer driven by an oncogene called KRAS can be treated after completely blocking IFG-1 signaling.

    IGF-1 signaling is a pathway that influences the uptake and release of nutrients and ultimately cell growth, according to the researchers.

    "Growth factors like IGF-1 tell cells that nutrients are around, so when you suppress their signaling, the tumor cells don't take up the amino acids," said Nada Kalaany, a researcher in Boston Children's Hospital and the paper's senior author.

    Kalaany's team used two groups of mice with KRAS-driven lung cancer. The second group has been deleted with two key genes, known as Irs1 and Irs2, which encode so-called "adaptor" proteins that are necessary for insulin/IGF-1 signaling.

    "Almost all animals in this lung cancer model typically die within 15 weeks of KRAS activation," said Kalaany. "But the ones that lost both Irs1 and Irs2 were completely fine, we saw almost no tumors at 10 to 15 weeks."

    Metabolic profiling revealed that tumor cells lacking Irs1/2 had significantly lower levels of essential amino acids, the building blocks of protein. Yet, outside the cells, amino acids were plentiful.

    But that's not the whole story. When tumor cells "think" that they are starved, according to Kalaany, they can compensate for this and break down their own proteins to generate amino acids.

    The researchers tried to inhibit the protein breakdown with existing drugs, such as chloroquine, which inhibits autophagy, and bortezomib, a proteasome inhibitor that is used to treat multiple myeloma.

    When Kalaany's team injected human tumor cells lacking Irs1/2 into mice, tumors didn't grow as well. When they added inhibitors of protein breakdown, growth was almost completely suppressed.

    "Our work tries to identify metabolic dependencies and vulnerabilities in tumors," said Kalaany.

    However, Kalaany warned that, though both types of drugs, as well as IGF-1 inhibitors, are well tolerated, care would need to be taken in dosing any combination therapy to avoid toxicities.

    Back to Top Close
    Xinhuanet

    Scientists develop a two-step approach to starve lung tumor cells

    Source: Xinhua 2018-04-03 04:39:00

    These two lung samples are from mice prone to develop Kras-mutant non-small-cell lung cancer. The lungs of mouse on the left are filled with tumors, as expected. The lung on the right, whose Kras-mutant cells have lost the Irs1/Irs2 genes, lacks the insulin/IGF-1 signaling needed for growth and is virtually devoid of tumors. (In a later stage, the tumors develop a workaround that enables them to start growing again.) (Credit: Clare (He) Xu, PhD, Boston Children's Hospital)

    WASHINGTON, April 2 (Xinhua) -- American scientists developed a two-prolonged therapy with a combination of drugs that are already available clinically to starve the tumor cells to death.

    The Boston Children's Hospital study, published on Monday in the Proceedings of the National Academy of Sciences, has shown that the non-small-cell lung cancer driven by an oncogene called KRAS can be treated after completely blocking IFG-1 signaling.

    IGF-1 signaling is a pathway that influences the uptake and release of nutrients and ultimately cell growth, according to the researchers.

    "Growth factors like IGF-1 tell cells that nutrients are around, so when you suppress their signaling, the tumor cells don't take up the amino acids," said Nada Kalaany, a researcher in Boston Children's Hospital and the paper's senior author.

    Kalaany's team used two groups of mice with KRAS-driven lung cancer. The second group has been deleted with two key genes, known as Irs1 and Irs2, which encode so-called "adaptor" proteins that are necessary for insulin/IGF-1 signaling.

    "Almost all animals in this lung cancer model typically die within 15 weeks of KRAS activation," said Kalaany. "But the ones that lost both Irs1 and Irs2 were completely fine, we saw almost no tumors at 10 to 15 weeks."

    Metabolic profiling revealed that tumor cells lacking Irs1/2 had significantly lower levels of essential amino acids, the building blocks of protein. Yet, outside the cells, amino acids were plentiful.

    But that's not the whole story. When tumor cells "think" that they are starved, according to Kalaany, they can compensate for this and break down their own proteins to generate amino acids.

    The researchers tried to inhibit the protein breakdown with existing drugs, such as chloroquine, which inhibits autophagy, and bortezomib, a proteasome inhibitor that is used to treat multiple myeloma.

    When Kalaany's team injected human tumor cells lacking Irs1/2 into mice, tumors didn't grow as well. When they added inhibitors of protein breakdown, growth was almost completely suppressed.

    "Our work tries to identify metabolic dependencies and vulnerabilities in tumors," said Kalaany.

    However, Kalaany warned that, though both types of drugs, as well as IGF-1 inhibitors, are well tolerated, care would need to be taken in dosing any combination therapy to avoid toxicities.

    010020070750000000000000011105091370837361
    主站蜘蛛池模板: 国产麻豆精品久久一二三| 日韩一区二区视频在线观看| 国产v片成人影院在线观看| 91精品国产亚洲爽啪在线影院| 无码人妻丰满熟妇区五十路百度| 亚洲人成网站999久久久综合| 精品一区精品二区制服| 国产成人免费视频app| 99久久人妻无码精品系列蜜桃| 手机在线视频你懂的| 亚洲va乱码一区二区三区| 狠狠噜天天噜日日噜视频麻豆| 国产suv精品一区二区33| 日本高清www无色夜在| 天天看片天天爽_免费播放| 久久久久久久97| 欧美丝袜一区二区三区| 人妻丰满熟妇av无码区| 色一情一乱一伦色一情一乱一伦| 国产狂喷潮在线观看在线观看 | 欧美精品一区二区三区免费观看| 和黑帮老大365天完整版免费| 黄色片视频国产| 国产精品成人免费视频电影| www.五月天婷婷| 打开腿给医生检查黄文| 久久精品日日躁夜夜躁欧美| 欧美成人鲁丝片在线观看| 免费在线h视频| 色www免费视频| 国产在线一区二区三区在线| 俺去俺也在线www色官网| 在线视频亚洲一区| 一区二区国产在线观看| 撒尿bbwbbw| 久久夜色精品国产欧美乱| 欧美一区二区三区精品影视| 亚洲码欧美码一区二区三区| 真实国产乱子伦对白视频37p| 国产91成人精品亚洲精品| 韩日美无码精品无码|