Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell growth.This pathway is activated in response to cell cycle arrest signals(cell polar...Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell growth.This pathway is activated in response to cell cycle arrest signals(cell polarity,transduction,and DNA damage)and limited by growth factors or mitogens associated with EGF and LPA.The major pathway consists of the central kinase of Ste20 MAPK(Saccharomyces cerevisiae),Hpo(Drosophila melanogaster)or MST kinases(mammalian)that activates the mammalian AGC kinase dmWts or LATS effector(MST and LATS).YAP in the nucleus work as a cofactor for a wide range of transcription factors involved in proliferation(TEA domain family,TEAD1-4),stem cells(Oct4 mononuclear factor and SMAD-related TGFb effector),differentiation(RUNX1),and Cell cycle/apoptosis control(p53,p63,and p73 family members).This is due to the diverse roles of YAP and may limit tumor progression and establishment.TEAD also coordinates various signal transduction pathways such as Hippo,WNT,TGFb and EGFR,and effects on lack of regulation of TEAD cancerous genes,such as KRAS,BRAF,LKB1,NF2 and MYC,which play essential roles in tumor progression,metastasis,cancer metabolism,immunity,and drug resistance.However,RAS signaling is a pivotal factor in the inactivation of Hippo,which controls EGFR-RAS-RAF-MEK-ERKmediated interaction of Hippo signaling.Thus,the loss of the Hippo pathway may have significant consequences on the targets of RAS-RAF mutations in cancer.展开更多
New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. ...New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer(NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor(CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities,starting with the U.S. Food and Drug Administration(FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.展开更多
文摘Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell growth.This pathway is activated in response to cell cycle arrest signals(cell polarity,transduction,and DNA damage)and limited by growth factors or mitogens associated with EGF and LPA.The major pathway consists of the central kinase of Ste20 MAPK(Saccharomyces cerevisiae),Hpo(Drosophila melanogaster)or MST kinases(mammalian)that activates the mammalian AGC kinase dmWts or LATS effector(MST and LATS).YAP in the nucleus work as a cofactor for a wide range of transcription factors involved in proliferation(TEA domain family,TEAD1-4),stem cells(Oct4 mononuclear factor and SMAD-related TGFb effector),differentiation(RUNX1),and Cell cycle/apoptosis control(p53,p63,and p73 family members).This is due to the diverse roles of YAP and may limit tumor progression and establishment.TEAD also coordinates various signal transduction pathways such as Hippo,WNT,TGFb and EGFR,and effects on lack of regulation of TEAD cancerous genes,such as KRAS,BRAF,LKB1,NF2 and MYC,which play essential roles in tumor progression,metastasis,cancer metabolism,immunity,and drug resistance.However,RAS signaling is a pivotal factor in the inactivation of Hippo,which controls EGFR-RAS-RAF-MEK-ERKmediated interaction of Hippo signaling.Thus,the loss of the Hippo pathway may have significant consequences on the targets of RAS-RAF mutations in cancer.
文摘New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer(NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor(CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities,starting with the U.S. Food and Drug Administration(FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.
