Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.

Abstract:

:Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy. In this report, we describe a sustained response of an unresectable multifocal form of adult medulloblastoma to vismodegib. Molecular analysis in this case revealed mutations in TP53 and a cytogenetic abnormality, i17q, that is prevalent and most often associated with subgroup 4 rather than the SHH-activated form of medulloblastoma. Our findings indicate that vismodegib may also block alternate, non-canonical forms of downstream SHH pathway activation. These findings provide strong impetus for further investigation of vismodegib in clinical trials in the first-line setting for pediatric and adult forms of medulloblastoma.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Lou E,Schomaker M,Wilson JD,Ahrens M,Dolan M,Nelson AC

doi

10.1080/15384047.2016.1220453

subject

Has Abstract

pub_date

2016-10-02 00:00:00

pages

1010-1016

issue

10

eissn

1538-4047

issn

1555-8576

journal_volume

17

pub_type

杂志文章
  • Functional characterization of NAD dependent de-acetylases SIRT1 and SIRT2 in B-Cell Chronic Lymphocytic Leukemia (CLL).

    abstract::Sirtuins (SIRT) are nicotinamide adenine dinucleotide (NAD+) dependent deacetylases or ADP- ribosyl transferases (ARTs) that deacetylate lysine residues on various proteins regulating a variety of cellular and metabolic processes. These enzymes regulate metabolism, cell survival, differentiation and DNA repair. SIRT p...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2016.1139246

    authors: Bhalla S,Gordon LI

    更新日期:2016-01-01 00:00:00

  • Enhanced growth inhibition and apoptosis induction in NSCLC cell lines by combination of celecoxib and 4HPR at clinically relevant concentrations.

    abstract::Celecoxib exhibits cancer preventive and therapeutic effects in animal models and clinical trials. It presumably acts through selective inhibition of cyclooxygenase-2 (COX-2) and subsequent reduction of prostaglandin (PG) synthesis. However, the concentrations of celecoxib required for growth inhibition and apoptosis ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.4.1618

    authors: Sun SY,Schroeder CP,Yue P,Lotan D,Hong WK,Lotan R

    更新日期:2005-04-01 00:00:00

  • E2F1 as a target: promoter-driven suicide and small molecule modulators.

    abstract::Decreased requirements for mitogens and diminished sensitivity to antiproliferative signals are among the hallmarks of human cancer. These attributes are due, at least partly, to mutations that directly or indirectly compromise the function of the retinoblastoma tumor suppressor protein (pRB), which is a negative regu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:

    authors: Kaelin WG Jr

    更新日期:2003-07-01 00:00:00

  • β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells.

    abstract::A greater understanding of the molecular basis of breast cancer metastasis will lead to identification of novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses the metastasis of breast cancer cells by increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1070988

    authors: Wilson JM,Lorimer E,Tyburski MD,Williams CL

    更新日期:2015-01-01 00:00:00

  • Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice.

    abstract::Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.6.1734

    authors: Xiao F,Crissey MA,Lynch JP,Kaestner KH,Silberg DG,Suh E

    更新日期:2005-06-01 00:00:00

  • Absence of SV40 in Austrian tumors correlates with low incidence of mesotheliomas.

    abstract::Between 1955 and 1963 millions of people were worldwide vaccinated with polio-vaccines that were contaminated with the simian virus 40 (SV40). This tumor-inducing virus has subsequently been detected in several human tumors. In Austria, polio mass vaccination started in winter 1961/62 with a presumably SV40-free Briti...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:

    authors: Leithner A,Weinhaeusel A,Windhager R,Schlegl R,Waldner P,Lang S,Dominkus M,Zoubek A,Popper HH,Haas OA

    更新日期:2002-07-01 00:00:00

  • Novel surface targets and serum biomarkers from the ovarian cancer vasculature.

    abstract::The molecular phenotype of tumor vasculature is different from normal vasculature, offering new opportunities for diagnosis and therapy of cancer, but the identification of tumor-restricted targets remains a challenge. We investigated 13 tumor vascular markers (TVMs) from 50 candidates identified through expression pr...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.3.16260

    authors: Sasaroli D,Gimotty PA,Pathak HB,Hammond R,Kougioumtzidou E,Katsaros D,Buckanovich R,Devarajan K,Sandaltzopoulos R,Godwin AK,Scholler N,Coukos G

    更新日期:2011-08-01 00:00:00

  • Knockdown of ezrin via RNA interference suppresses Helicobacter pylori-enhanced invasion of gastric cancer cells.

    abstract:BACKGROUND AND AIM:H. pylori interacts with gastric epithelial cells, which may activate signaling pathways important for gastric cancer invasion. Ezrin, a membrane cytoskeletal crosslinker protein, is well documented to regulate cell adhesion and cell motility. The aim of the present study was to determine whether ezr...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.11.8.14691

    authors: Fan LL,Chen DF,Lan CH,Liu KY,Fang DC

    更新日期:2011-04-15 00:00:00

  • Acquired resistance of lung adenocarcinoma to EGFR-tyrosine kinase inhibitors gefitinib and erlotinib.

    abstract::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are the first targeted therapy drugs approved for the treatment of advanced non-small-cell lung cancer (NSCLC). Interestingly, treatment with these small molecule, reversible EGFR-TKIs leads to more positive respo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.9.8.11881

    authors: Xu Y,Liu H,Chen J,Zhou Q

    更新日期:2010-04-15 00:00:00

  • Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1, a novel epithelial-mesenchymal transition inducer in pancreatic cancer.

    abstract::Epithelial-mesenchymal transition (EMT) is a critical early event in tumorigenesis. The contribution of heparan sulfate (HS) to EMT has not been fully elucidated. HS D-glucosaminyl 3-O-sulfotransferase-3B1 (3-OST-3B1) participates in the final step of HS fine structure biosynthesis, whose involvement in cancer has yet...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.5.15957

    authors: Song K,Li Q,Jiang ZZ,Guo CW,Li P

    更新日期:2011-09-01 00:00:00

  • Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: implication for breast carcinogenesis.

    abstract::Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogene...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.13.2.18873

    authors: Weisz J,Shearer DA,Murata E,Patrick SD,Han B,Berg A,Clawson GA

    更新日期:2012-01-15 00:00:00

  • Inactivation of miR-100 combined with arsenic treatment enhances the malignant transformation of BEAS-2B cells via stimulating epithelial -mesenchymal transition.

    abstract::Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1345393

    authors: Yang J,Chen Z,Wang X,Xu M,Fang H,Li F,Liu Y,Jiang Y,Ding Y,Li J,Wang S

    更新日期:2017-12-02 00:00:00

  • Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21.

    abstract::Recent research has found that long noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in cervical cancer remains unexplored. Therefore, we aimed to investigate the biological function of maternally expressed gene 3 (MEG3), a cancer-related lncRNA, and its underlying me...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1108496

    authors: Zhang J,Yao T,Wang Y,Yu J,Liu Y,Lin Z

    更新日期:2016-01-01 00:00:00

  • Chimeric cytokine receptor enhancing PSMA-CAR-T cell-mediated prostate cancer regression.

    abstract::Objective: Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated an unprecedented therapeutic efficacy in hematological malignancies; however, its effectiveness in solid tumors remains elusive. In order to enable CAR-T cells more effective to solid tumors, a inverted chimeric cytokine receptor (ICR) was de...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2020.1739952

    authors: Weimin S,Abula A,Qianghong D,Wenguang W

    更新日期:2020-06-02 00:00:00

  • ETS-TMPRSS2 fusion gene products in prostate cancer.

    abstract::Genes playing a role in carcinogenesis have often been identified through analysis of recurrent chromosomal rearrangements. Although such rearrangements are well known in leukemias, lymphomas, and sarcomas, they have not been well characterized in carcinomas. In the October 28, 2005 issue of Science, a study by Tomlin...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.3.2603

    authors: Ahlers CM,Figg WD

    更新日期:2006-03-01 00:00:00

  • Rapamycin enhances cetuximab cytotoxicity by inhibiting mTOR-mediated drug resistance in mesenchymal hepatoma cells.

    abstract::The synergistic effect of combined drug therapy provides an enhanced treatment for advanced liver cancer. We aimed to investigate the underlying mechanism of cetuximab sensitization by rapamycin in hepatoma cells. Four hepatoma cell lines, HepG2, HuH7, SNU-387, and SNU-449, were treated with cetuximab or cetuximab plu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.29113

    authors: Chen W,Hu QD,Xia XF,Liang C,Liu H,Zhang Q,Ma T,Liang F,Liang TB

    更新日期:2014-08-01 00:00:00

  • Downregulation of lncRNA ANRIL inhibits proliferation, induces apoptosis, and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a.

    abstract::Increasing evidence demonstrated that long non-coding RNA ANRIL serves as a fatal oncogene in many cancers, including nasopharyngeal carcinoma (NPC). However, little is known whether ANRIL regulated NPC cell radioresistance. Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA ANRIL a...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1310348

    authors: Hu X,Jiang H,Jiang X

    更新日期:2017-05-04 00:00:00

  • Concomitant activation of the JAK/STAT3 and ERK1/2 signaling is involved in leptin-mediated proliferation of renal cell carcinoma Caki-2 cells.

    abstract::Obesity is considered one of the risk factors for many cancers. Serum leptin levels are often elevated in obese people. Leptin has been reported to act as a mitogenic agent and promote renal cancer cell proliferation, whereas the detailed mechanisms still remain to be elucidated. The purpose of this study is to invest...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.11.6837

    authors: Li L,Gao Y,Zhang LL,He DL

    更新日期:2008-11-01 00:00:00

  • Mitogen-activated protein kinase phosphatase-1 inhibition and sustained extracellular signal-regulated kinase 1/2 activation in camptothecin-induced human colon cancer cell death.

    abstract::Camptothecins are commonly used chemotherapeutics; in some models, they enhance signaling via the mitogen-activated protein kinase (MAPK) pathway through effects on upstream kinases. To evaluate the impact of camptothecin (CPT) on MAPKs in human colon cancer, we studied HCT116 and CaCo2 colon cancer cells. We found th...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.26044

    authors: Lee M,Young Kim S,Kim J,Kim HS,Kim SM,Kim EJ

    更新日期:2013-11-01 00:00:00

  • Myriocin, a serine palmitoyltransferase inhibitor, suppresses tumor growth in a murine melanoma model by inhibiting de novo sphingolipid synthesis.

    abstract::Advanced melanoma is the most virulent form of cancer and has a poor prognosis. In a previous study, myriocin, an inhibitor of serine palmitoyltransferase, was found to suppress melanoma cell proliferation by cell cycle arrest at the G 2/M phase through decreased sphingolipid levels and increased p53 and p21 (waf1/cip...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.13.2.18870

    authors: Lee YS,Choi KM,Lee S,Sin DM,Lim Y,Lee YM,Hong JT,Yun YP,Yoo HS

    更新日期:2012-01-15 00:00:00

  • BRCA1 phosphorylation: biological consequences.

    abstract::More than a decade has passed since BRCA1, breast cancer tumor suppressor 1, was isolated by reverse genetics in 1994. Its molecular structure and potential function have been extensively studied; both mouse genetics and a cell culture system revealed that BRCA1 is a 220,240 kD nuclear phosphoprotein, it regulates tra...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.5.5.2845

    authors: Ouchi T

    更新日期:2006-05-01 00:00:00

  • Probiotics, prebiotics and synbiotics: a role in chemoprevention for colorectal cancer?

    abstract::Colorectal cancer (CRC) is the third most common form of cancer. Current treatments including chemotherapy, radiotherapy and surgery are all associated with a high risk of complications and are not always successful, highlighting the need to develop new treatment strategies. The ingestion of probiotics, prebiotics or ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.5.10.3296

    authors: Geier MS,Butler RN,Howarth GS

    更新日期:2006-10-01 00:00:00

  • Translational control of gene expression during hypoxia.

    abstract::Poor oxygenation is a unique and prevalent feature of solid tumors associated with poor patient prognosis. In part, this is caused by a series of adaptive cellular responses that together have a large impact on gene expression and cell phenotype. HIF plays a key role in this response by activating a transcriptional pr...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.5.7.2972

    authors: van den Beucken T,Koritzinsky M,Wouters BG

    更新日期:2006-07-01 00:00:00

  • IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.

    abstract::Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formati...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.3.3702

    authors: Ruan W,Xu E,Xu F,Ma Y,Deng H,Huang Q,Lv B,Hu H,Lin J,Cui J,Di M,Dong J,Lai M

    更新日期:2007-03-01 00:00:00

  • Sunitinib inhibits papillary thyroid carcinoma with RET/PTC rearrangement but not BRAF mutation.

    abstract::Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated into the management of papillary thyroid carcinoma refractory to standard therapies. Although clinical trials are in progress, the mechanism of action in papillary thyroid carcinomas is not clear, especially regarding the effect on BRAF ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.5.16303

    authors: Jeong WJ,Mo JH,Park MW,Choi IJ,An SY,Jeon EH,Ahn SH

    更新日期:2011-09-01 00:00:00

  • Daunomycin, an antitumor DNA intercalator, influences histone-DNA interactions.

    abstract::Although daunomycin and adriamycin are considered effective antitumor drugs and have been used in the clinic for over 40 years, their mechanism of action is still a matter of debate. We investigated the influence of daunomycin on interaction between linker or core histones and DNA in live HeLa cells in vitro, using im...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.25328

    authors: Wójcik K,Zarębski M,Cossarizza A,Dobrucki JW

    更新日期:2013-09-01 00:00:00

  • Colorectal cancer: new advances in immunotherapy.

    abstract::Colorectal cancer remains the second leading cause of cancer-related mortality in the United States. Although surgical resection is still the primary treatment for colorectal cancer, in recent years, there has been a remarkable progress in the development of new therapies to treat colorectal cancer. Response rates hav...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.6.1.3672

    authors: Cubas R,Li M,Chen C,Yao Q

    更新日期:2007-01-01 00:00:00

  • KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression.

    abstract::Krüppel-Like Factor 4 (KLF4) functions as a tumor suppressor in some cancers, but its molecular mechanism is not clear. Our recent study also showed that the expression of KLF4 is dramatically reduced in primary lung cancer tissues. To investigate the possible role of KLF4 in lung cancer, we stably transfected KLF4 in...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.9.7.11106

    authors: Zhou Y,Hofstetter WL,He Y,Hu W,Pataer A,Wang L,Wang J,Zhou Y,Yu L,Fang B,Swisher SG

    更新日期:2010-04-01 00:00:00

  • Combined endostatin and TRAIL gene transfer suppresses human hepatocellular carcinoma growth and angiogenesis in nude mice.

    abstract::Endostatin can inhibit tumor growth by blocking angiogenesis, whereas tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill cancer cells without toxicity to most normal cells. To establish the combined anti-tumor therapeutic effect of endostatin and solu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.8.5.7687

    authors: Zhang Y,Qu ZH,Cui M,Guo C,Zhang XM,Ma CH,Sun WS

    更新日期:2009-03-01 00:00:00

  • Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma.

    abstract::Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive che...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2016.1235664

    authors: Beck A,Eberherr C,Hagemann M,Cairo S,Häberle B,Vokuhl C,von Schweinitz D,Kappler R

    更新日期:2016-11-01 00:00:00