Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2.

abstract：:Bortezomib is highly effective in the treatment of multiple myeloma; however, emergent drug resistance is common. Consequently, we employed CRISPR targeting 19,052 human genes to identify unbiased targets that contribute to bortezomib resistance. Specifically, we engineered an RPMI8226 multiple myeloma cell line to ex...

journal_title：Molecular cancer therapeutics

authors： Shi CX,Kortüm KM,Zhu YX,Bruins LA,Jedlowski P,Votruba PG,Luo M,Stewart RA,Ahmann J,Braggio E,Stewart AK

更新日期：2017-12-01 00:00:00

abstract：:Increasing literature suggests that cell adhesion molecule alpha4beta1 integrin plays a pivotal role in autoimmune diseases and cancer development. Noninvasive visualization of alpha4beta1 integrin in vivo will facilitate the understanding of its involvement in disease progression and development of targeted therapies...

journal_title：Molecular cancer therapeutics

authors： Peng L,Liu R,Andrei M,Xiao W,Lam KS

更新日期：2008-02-01 00:00:00

abstract：:The cytosine analogue decitabine alters hematopoietic differentiation. For example, decitabine treatment increases self-renewal of normal hematopoietic stem cells. The mechanisms underlying decitabine-induced shifts in differentiation are poorly understood, but likely relate to the ability of decitabine to deplete the...

journal_title：Molecular cancer therapeutics

authors： Hu Z,Negrotto S,Gu X,Mahfouz R,Ng KP,Ebrahem Q,Copelan E,Singh H,Maciejewski JP,Saunthararajah Y

更新日期：2010-06-01 00:00:00

abstract：:Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor, and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14...

journal_title：Molecular cancer therapeutics

authors： Morgan KM,Fischer BS,Lee FY,Shah JJ,Bertino JR,Rosenfeld J,Singh A,Khiabanian H,Pine SR

更新日期：2017-12-01 00:00:00

abstract：:In breast and certain other cancers, receptor tyrosine kinases, including the insulin-like growth factor I receptor (IGF-IR), play an important role in promoting the oncogenic process. The IGF-IR is therefore an important target for developing new anti-breast cancer therapies. An initial screening of a chemical librar...

journal_title：Molecular cancer therapeutics

authors： Gable KL,Maddux BA,Penaranda C,Zavodovskaya M,Campbell MJ,Lobo M,Robinson L,Schow S,Kerner JA,Goldfine ID,Youngren JF

更新日期：2006-04-01 00:00:00

abstract：:Anti-HER2/CD3, a T-cell-dependent bispecific antibody (TDB) construct, induces T-cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of m...

journal_title：Molecular cancer therapeutics

authors： Mandikian D,Takahashi N,Lo AA,Li J,Eastham-Anderson J,Slaga D,Ho J,Hristopoulos M,Clark R,Totpal K,Lin K,Joseph SB,Dennis MS,Prabhu S,Junttila TT,Boswell CA

更新日期：2018-04-01 00:00:00

abstract：:1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes containing p-trifluoromethyl, t-butyl, and phenyl [1,1-bis(3'-indolyl)-1-(p-phenyl)methane (DIM-C-pPhC(6)H(5))] substituents induce peroxisome proliferator-activated receptor gamma (PPARgamma)-mediated transactivation in SW480 colon cancer cells. These PPARgamma-act...

journal_title：Molecular cancer therapeutics

authors： Chintharlapalli S,Papineni S,Safe S

更新日期：2006-05-01 00:00:00

abstract：:Multiple roles within mitosis have been assigned to Polo-like kinase 1 (Plk1), making it an attractive candidate for mitotic targeting of cancer cells. We have employed chimeric antisense oligonucleotides to investigate the molecular alterations after targeted interference with Plk1 in RKO human colon adenocarcinoma a...

journal_title：Molecular cancer therapeutics

authors： Schmidt M,Hofmann HP,Sanders K,Sczakiel G,Beckers TL,Gekeler V

更新日期：2006-04-01 00:00:00

abstract：:Despite frequent overexpression of numerous growth factor receptors by pancreatic ductal adenocarcinomas (PDAC), such as EGFR, therapeutic antibodies have not proven effective. Desmoplasia, hypovascularity, and hypoperfusion create a functional drug delivery barrier that contributes to treatment resistance. Drug combi...

journal_title：Molecular cancer therapeutics

authors： Wang J,Chan DKW,Sen A,Ma WW,Straubinger RM

更新日期：2019-11-01 00:00:00

abstract：:Breast cancer is one of the leading causes of cancer deaths among females. Many challenges exist in the current management of advanced stage breast cancer as there are fewer recognized therapeutic strategies, often because of therapy resistance. How breast cancer cells evade chemotherapy and the underlying mechanism r...

journal_title：Molecular cancer therapeutics

authors： Sharma B,Nawandar DM,Nannuru KC,Varney ML,Singh RK

更新日期：2013-05-01 00:00:00

abstract：:The p53 inactivation caused by aberrant expression of its major regulators (e.g., MDM2 and MDMX) contributes to the genesis of a large number of human cancers. Recent studies have shown that restoration of p53 activity by counteracting p53 repressors is a promising anticancer strategy. Although agents (e.g., nutlin-3a...

journal_title：Molecular cancer therapeutics

authors： Wang H,Ma X,Ren S,Buolamwini JK,Yan C

更新日期：2011-01-01 00:00:00

abstract：:Anti-HER2 monoclonal antibodies (mAb) have been shown to reduce tumor size and increase survival in patients with breast cancer, but they are ineffective against brain metastases due to poor brain penetration. In previous studies, we identified a peptide, known as Angiopep-2 (An2), which crosses the blood-brain barrie...

journal_title：Molecular cancer therapeutics

authors： Regina A,Demeule M,Tripathy S,Lord-Dufour S,Currie JC,Iddir M,Annabi B,Castaigne JP,Lachowicz JE

更新日期：2015-01-01 00:00:00

abstract：:Novel therapeutic approaches are urgently needed for high-stage neuroblastoma, a major therapeutic challenge in pediatric oncology. The majority of neuroblastoma tumors are p53 wild type with intact downstream p53 signaling pathways. We hypothesize that stabilization of p53 would sensitize this aggressive tumor to gen...

journal_title：Molecular cancer therapeutics

authors： Barbieri E,Mehta P,Chen Z,Zhang L,Slack A,Berg S,Shohet JM

更新日期：2006-09-01 00:00:00

abstract：:The epithelial-mesenchymal transition (EMT) is a process associated with the metastasis of solid tumors as well as with the acquisition of resistance to standard anticancer modalities. A major initiator of EMT in carcinoma cells is TGF-β, which has been shown to induce the expression of several transcription factors u...

journal_title：Molecular cancer therapeutics

authors： Larocca C,Cohen JR,Fernando RI,Huang B,Hamilton DH,Palena C

更新日期：2013-09-01 00:00:00

abstract：:Dietary phytochemicals exhibit chemopreventive potential in vivo through persistent low-dose exposures, whereas mechanistic in vitro studies with these agents generally use a high-dose single treatment. Because the latter approach is not representative of an in vivo steady state, we investigated antitumor activity of ...

journal_title：Molecular cancer therapeutics

authors： Moiseeva EP,Almeida GM,Jones GD,Manson MM

更新日期：2007-11-01 00:00:00

abstract：:The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived canna...

journal_title：Molecular cancer therapeutics

authors： Marcu JP,Christian RT,Lau D,Zielinski AJ,Horowitz MP,Lee J,Pakdel A,Allison J,Limbad C,Moore DH,Yount GL,Desprez PY,McAllister SD

更新日期：2010-01-01 00:00:00

abstract：:Using the "one-bead one-peptide" combinatorial technology, a library of random cyclic octapeptides and nonapeptides, consisting of natural and unnatural amino acids, was synthesized on polystyrene beads. This library was used to screen for peptides that promoted attachment and proliferation of bronchioloalveolar carci...

journal_title：Molecular cancer therapeutics

authors： Mikawa M,Wang H,Guo L,Liu R,Marik J,Takada Y,Lam K,Lau D

更新日期：2004-10-01 00:00:00

abstract：:Soft-tissue sarcomas (STS) represent a heterogeneous group of rare, malignant tumors of mesenchymal origin. Reliable in vivo sarcoma research models are scarce. We aimed to establish and characterize histologically and molecularly stable patient-derived xenograft (PDX) models from a broad variety of STS subtypes. A to...

journal_title：Molecular cancer therapeutics

authors： Cornillie J,Wozniak A,Li H,Wang Y,Boeckx B,Gebreyohannes YK,Wellens J,Vanleeuw U,Hompes D,Stas M,Sinnaeve F,Wafa H,Lambrechts D,Debiec-Rychter M,Sciot R,Schöffski P

更新日期：2019-06-01 00:00:00

abstract：:Aberrant activation of Notch and Ras pathways has been detected in breast cancers. A synergy between these two pathways has also been shown in breast cell transformation in culture. Yet, the clinical relevance of Notch-Ras cooperation in breast cancer progression remains unexplored. In this study, we show that coordin...

journal_title：Molecular cancer therapeutics

authors： Mittal S,Sharma A,Balaji SA,Gowda MC,Dighe RR,Kumar RV,Rangarajan A

更新日期：2014-12-01 00:00:00

abstract：:Hsp90 is widely overexpressed in cancer cells and believed to be essential for the maintenance of malignant phenotypes. Targeting Hsp90 by small molecules has shown promise in solid and hematologic malignancies, which likely involves degradation of client oncoproteins in a cell-type-specific manner. In this study, we ...

journal_title：Molecular cancer therapeutics

authors： He K,Zheng X,Zhang L,Yu J

更新日期：2013-11-01 00:00:00

abstract：:Chemoresistance is a major reason that patients with osteosarcoma fail to achieve a lasting chemotherapy response, and it contributes to disease relapse, progression, and death. Human glutathione S-transferase P1 (GSTP1), a phase II detoxification enzyme, contributes to chemoresistance in many cancers. However, the ro...

journal_title：Molecular cancer therapeutics

authors： Huang G,Mills L,Worth LL

更新日期：2007-05-01 00:00:00

abstract：:Replication protein A (RPA) is a single-strand DNA-binding protein with essential roles in DNA replication, recombination, and repair. It is necessary for the formation of the preincision complex that is required for proper incision of damaged DNA nucleotides during DNA repair. We have previously identified small mole...

journal_title：Molecular cancer therapeutics

authors： Neher TM,Bodenmiller D,Fitch RW,Jalal SI,Turchi JJ

更新日期：2011-10-01 00:00:00

abstract：:Glioblastoma is the most frequent brain tumor of glial origin in adults. With the best available standard-of-care, patients with this disease have a life expectancy of only approximately 15 months after diagnosis. Because the EGF receptor (HER1/EGFR) is one of the most commonly dysregulated oncogenes in glioblastoma, ...

journal_title：Molecular cancer therapeutics

authors： Karpel-Massler G,Westhoff MA,Zhou S,Nonnenmacher L,Dwucet A,Kast RE,Bachem MG,Wirtz CR,Debatin KM,Halatsch ME

更新日期：2013-09-01 00:00:00

abstract：:Despite significant advances in combinations of radiotherapy and chemotherapy, altered fractionation schedules and image-guided radiotherapy, many cancer patients fail to benefit from radiation. A prevailing hypothesis is that targeting repair of DNA double strand breaks (DSB) can enhance radiation effects in the tumo...

journal_title：Molecular cancer therapeutics

authors： Efimova EV,Ricco N,Labay E,Mauceri HJ,Flor AC,Ramamurthy A,Sutton HG,Weichselbaum RR,Kron SJ

更新日期：2018-02-01 00:00:00

abstract：:Mitotic spindle poisons (e.g., Taxol and vinblastine), used as chemotherapy drugs, inhibit mitotic spindle function, activate the mitotic spindle checkpoint, arrest cells in mitosis, and then cause cell death by mechanisms that are poorly understood. By expression cloning, we identified a truncated version of human TR...

journal_title：Molecular cancer therapeutics

authors： Yamada HY,Gorbsky GJ

更新日期：2006-01-01 00:00:00

abstract：:Barasertib (AZD1152), a highly potent and selective aurora kinase B inhibitor, gave promising clinical activity in elderly acute myeloid leukemia (AML) patients. However, clinical utility was limited by the requirement for a 7-day infusion. Here we assessed the potential of a nanoparticle formulation of the selective ...

journal_title：Molecular cancer therapeutics

authors： Floc'h N,Ashton S,Taylor P,Trueman D,Harris E,Odedra R,Maratea K,Derbyshire N,Caddy J,Jacobs VN,Hattersley M,Wen S,Curtis NJ,Pilling JE,Pease EJ,Barry ST

更新日期：2017-06-01 00:00:00

abstract：:Recent studies have shown that up to 90% of viral vectors could disseminate to normal organs following intratumoral infusion. The amount of dissemination might be dependent on the infusion conditions. Therefore, we investigated the effects of infusion rate, volume, and dose on transgene expression in liver and tumor t...

journal_title：Molecular cancer therapeutics

authors： Wang Y,Wang H,Li CY,Yuan F

更新日期：2006-02-01 00:00:00

abstract：:We previously reported that angiotensin II type 1 receptor (AT1R) antagonists enhanced the cytotoxity of cis-dichlorodiammineplatinum (CDDP) in a bladder cancer xenograft model. To elucidate the synergistic mechanism, we investigated whether reactive oxygen species (ROS) generation induced by CDDP may affect the regul...

journal_title：Molecular cancer therapeutics

authors： Tanaka N,Miyajima A,Kosaka T,Shirotake S,Hasegawa M,Kikuchi E,Oya M

更新日期：2010-11-01 00:00:00

abstract：:Staphylococcal nuclease domain-containing protein 1 (SND1) is a multifunctional oncoprotein overexpressed in breast cancer. Binding of metadherin (MTDH) to SND1 results in the stabilization of SND1 and is important in the initiation and progression of breast cancer. Disruption of such interaction is a potential therap...

journal_title：Molecular cancer therapeutics

authors： Li P,He Y,Chen T,Choy KY,Chow TS,Wong ILK,Yang X,Sun W,Su X,Chan TH,Chow LMC

更新日期：2021-01-01 00:00:00

abstract：:Given the bulky nature of nanotherapeutics relative to small molecules, it is hypothesized that effective tumor delivery and penetration are critical barriers to their clinical activity. HER2-targeted PEGylated liposomal doxorubicin (MM-302, HER2-tPLD) is an antibody-liposomal drug conjugate designed to deliver doxoru...

journal_title：Molecular cancer therapeutics

authors： Geretti E,Leonard SC,Dumont N,Lee H,Zheng J,De Souza R,Gaddy DF,Espelin CW,Jaffray DA,Moyo V,Nielsen UB,Wickham TJ,Hendriks BS

更新日期：2015-09-01 00:00:00