Novel inhibitors of cyclin-dependent kinases combat hepatocellular carcinoma without inducing chemoresistance.

abstract：:We have synthesized several new phenyl maleimide compounds, which are potent growth inhibitors of several human tumor cell lines. Among these, PM-20 was the most potent with an IC50 of 700 nmol/L for Hep3B human hepatoma cell growth. Two other derivatives, PM-26 and PM-38, did not inhibit Hep3B cell growth even at 100...

journal_title：Molecular cancer therapeutics

authors： Kar S,Wang M,Yao W,Michejda CJ,Carr BI

更新日期：2006-06-01 00:00:00

abstract：:Castration-resistant prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active, ligand-independent variants is one of the principal mechanisms that promote the development of resistance to next-generation antiandrogens such as enzalut...

journal_title：Molecular cancer therapeutics

authors： Nadiminty N,Tummala R,Liu C,Lou W,Evans CP,Gao AC

更新日期：2015-08-01 00:00:00

abstract：:HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I in...

journal_title：Molecular cancer therapeutics

authors： Koganemaru S,Kuboki Y,Koga Y,Kojima T,Yamauchi M,Maeda N,Kagari T,Hirotani K,Yasunaga M,Matsumura Y,Doi T

更新日期：2019-11-01 00:00:00

abstract：:Localized activation of the prodrug ifosfamide in or close to tumors by implanting encapsulated ifosfamide-activating cells is an efficacious strategy for tumor therapy. The aim of this study was to evaluate the feasibility of subsieve-size agarose capsules for enclosing the cells in this application. Compared with ma...

journal_title：Molecular cancer therapeutics

authors： Sakai S,Kawabata K,Tanaka S,Harimoto N,Hashimoto I,Mu C,Salmons B,Ijima H,Kawakami K

更新日期：2005-11-01 00:00:00

abstract：PURPOSE:Expression of the type 1 insulin-like growth factor receptor (IGF1R) confers adverse prognosis in clear cell renal cell cancer (CC-RCC). We recently showed that IGF1R expression is inhibited by the von Hippel-Lindau (VHL) tumor suppressor, and the IGF1R is up-regulated in CC-RCC, in which VHL is frequently inac...

journal_title：Molecular cancer therapeutics

authors： Yuen JS,Akkaya E,Wang Y,Takiguchi M,Peak S,Sullivan M,Protheroe AS,Macaulay VM

更新日期：2009-06-01 00:00:00

abstract：:Radiosensitization caused by the poly(ADP-ribose) polymerase (PARP) inhibitor 4-amino-1,8-naphthalimide (ANI) was investigated in 10 asynchronously growing rodent (V79, CHO-Xrs6, CHO-K1, PARP-1+/+ 3T3, and PARP-1-/- 3T3) or human (HeLa, MRC5VI, IMR90, M059J, and M059K) cell lines, either repair proficient or defective...

journal_title：Molecular cancer therapeutics

authors： Noël G,Godon C,Fernet M,Giocanti N,Mégnin-Chanet F,Favaudon V

更新日期：2006-03-01 00:00:00

abstract：:Acquired resistance severely hinders the application of small-molecule inhibitors. Our understanding of acquired resistance related to FGFRs is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors (FGFRi) and i...

journal_title：Molecular cancer therapeutics

authors： Wang X,Ai J,Liu H,Peng X,Chen H,Chen Y,Su Y,Shen A,Huang X,Ding J,Geng M

更新日期：2019-03-01 00:00:00

abstract：:The application of cancer gene therapy has heretofore been restricted to local, or locoregional, neoplastic disease contexts. This is owing to the lack of gene transfer vectors, which embody the requisite target cell selectivity in vivo required for metastatic disease applications. To this end, we have explored novel ...

journal_title：Molecular cancer therapeutics

authors： Lee M,Lu ZH,Li J,Kashentseva EA,Dmitriev IP,Mendonca SA,Curiel DT

更新日期：2020-03-01 00:00:00

abstract：:The type I EGF receptor (EGFR or ErbB1) and insulin-like growth factor-binding protein-3 (IGFBP-3) are highly expressed in triple-negative breast cancer (TNBC), a particularly aggressive disease that cannot be treated with conventional therapies targeting the estrogen or progesterone receptors (ER and PR), or HER2. We...

journal_title：Molecular cancer therapeutics

authors： Martin JL,de Silva HC,Lin MZ,Scott CD,Baxter RC

更新日期：2014-02-01 00:00:00

abstract：:Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selec...

journal_title：Molecular cancer therapeutics

authors： de Oliveira CE,Gasparoto TH,Pinheiro CR,Amôr NG,Nogueira MRS,Kaneno R,Garlet GP,Lara VS,Silva JS,Cavassani KA,Campanelli AP

更新日期：2017-12-01 00:00:00

abstract：:Antibody-drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of drugs to neoplastic cells. We have used this technology to develop the ADC DCDT2980S that targets CD22, an antigen with expression limited to B cells and the vast majority of non-Hodgkin lympho...

journal_title：Molecular cancer therapeutics

authors： Li D,Poon KA,Yu SF,Dere R,Go M,Lau J,Zheng B,Elkins K,Danilenko D,Kozak KR,Chan P,Chuh J,Shi X,Nazzal D,Fuh F,McBride J,Ramakrishnan V,de Tute R,Rawstron A,Jack AS,Deng R,Chu YW,Dornan D,Williams M,Ho W,

更新日期：2013-07-01 00:00:00

abstract：:Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-...

journal_title：Molecular cancer therapeutics

authors： Zhang Q,Bhola NE,Lui VW,Siwak DR,Thomas SM,Gubish CT,Siegfried JM,Mills GB,Shin D,Grandis JR

更新日期：2007-04-01 00:00:00

abstract：:Several studies have evaluated the efficacy of using human oncolytic adenovirus (OAdv)-loaded mesenchymal stem cells (MSC) for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow-mesenchymal stem cells infected with the OAdv ICOVIR-5, for treatment of patients wit...

journal_title：Molecular cancer therapeutics

authors： Moreno R,Fajardo CA,Farrera-Sal M,Perisé-Barrios AJ,Morales-Molina A,Al-Zaher AA,García-Castro J,Alemany R

更新日期：2019-01-01 00:00:00

abstract：:Gallium nitrate is a metallodrug with clinical efficacy in non-Hodgkin's lymphoma. Its mechanisms of antineoplastic action are not fully understood. In the present study, we investigated the roles of transferrin receptor (TfR) targeting and apoptotic pathways in gallium-induced cell death. Although DoHH2 lymphoma cell...

journal_title：Molecular cancer therapeutics

authors： Chitambar CR,Wereley JP,Matsuyama S

更新日期：2006-11-01 00:00:00

abstract：:Because proliferation of eukaryotic cells requires cell cycle-regulated chromatid separation by the mitotic spindle, it is subject to regulation by mitotic checkpoints. To determine the mechanism of the antiproliferative activity of the flavoprotein-specific inhibitor diphenyleneiodonium (DPI), I have examined its eff...

journal_title：Molecular cancer therapeutics

authors： Scaife RM

更新日期：2004-10-01 00:00:00

abstract：:Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that promotes malignant glioma invasion, angiogenesis, and immunosuppression. Antisense oligonucleotide suppression of TGF-beta(2) ligand expression has shown promise in preclinical and clinical studies but at least two ligands mediate the effect...

journal_title：Molecular cancer therapeutics

authors： Hjelmeland MD,Hjelmeland AB,Sathornsumetee S,Reese ED,Herbstreith MH,Laping NJ,Friedman HS,Bigner DD,Wang XF,Rich JN

更新日期：2004-06-01 00:00:00

abstract：:Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower ...

journal_title：Molecular cancer therapeutics

authors： Laquente B,Lacasa C,Ginestà MM,Casanovas O,Figueras A,Galán M,Ribas IG,Germà JR,Capellà G,Viñals F

更新日期：2008-03-01 00:00:00

abstract：:Bifunctional antibody fusion proteins engaging effector T cells for targeted elimination of tumor cells via CD3 binding have shown efficacy in both preclinical and clinical studies. Different from such a polyclonal T-cell recruitment, an alternative concept is to engage only antigen-specific T-cell subsets. Recruitmen...

journal_title：Molecular cancer therapeutics

authors： Schmittnaegel M,Hoffmann E,Imhof-Jung S,Fischer C,Drabner G,Georges G,Klein C,Knoetgen H

更新日期：2016-09-01 00:00:00

abstract：:Mutations in ERK signaling drive a significant percentage of malignancies. LY3009120, a pan-RAF and dimer inhibitor, has preclinical activity in RAS- and BRAF-mutated cell lines including BRAF-mutant melanoma resistant to BRAF inhibitors. This multicenter, open-label, phase I clinical trial (NCT02014116) consisted of ...

journal_title：Molecular cancer therapeutics

authors： Sullivan RJ,Hollebecque A,Flaherty KT,Shapiro GI,Rodon Ahnert J,Millward MJ,Zhang W,Gao L,Sykes A,Willard MD,Yu D,Schade AE,Crowe K,Flynn DL,Kaufman MD,Henry JR,Peng SB,Benhadji KA,Conti I,Gordon MS,Tiu RV,Hong

更新日期：2020-02-01 00:00:00

abstract：:Human antigen R (HuR) is an RNA-binding protein that posttranscriptionally regulates many cancer-trait genes. CDC6, a central regulator of DNA replication, is regulated by HuR. In this study, we investigated the role of HuR in colorectal cancer tumorigenesis and oxaliplatin (L-OHP) resistance, as well as the underlyin...

journal_title：Molecular cancer therapeutics

authors： Cai J,Wang H,Jiao X,Huang R,Qin Q,Zhang J,Chen H,Feng D,Tian X,Wang H

更新日期：2019-07-01 00:00:00

abstract：:Acute myeloid leukemia (AML) with Fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation is notoriously hard to treat. We identified two drugs that together form an effective combination therapy against FLT3-ITD AML. One of the drugs, Sorafenib, an inhibitor of FLT3-ITD and other kinase activity...

journal_title：Molecular cancer therapeutics

authors： Wang R,Li Y,Gong P,Gabrilove J,Waxman S,Jing Y

更新日期：2018-09-01 00:00:00

abstract：:Upregulation of HER2 is a hallmark of 20% to 30% of invasive breast cancers, rendering this receptor an attractive target for cancer therapy. Although HER2-targeting agents have provided substantial clinical benefit as cancer therapeutics, there is a need for the development of new agents aiming at circumventing anti-...

journal_title：Molecular cancer therapeutics

authors： Brack S,Attinger-Toller I,Schade B,Mourlane F,Klupsch K,Woods R,Hachemi H,von der Bey U,Koenig-Friedrich S,Bertschinger J,Grabulovski D

更新日期：2014-08-01 00:00:00

abstract：:Tivantinib (ARQ197) was first reported as a highly selective inhibitor of c-MET and is currently being investigated in a phase III clinical trial. However, as recently reported by us and another group, tivantinib showed cytotoxic activity independent of cellular c-MET status and also disrupted microtubule dynamics. To...

journal_title：Molecular cancer therapeutics

authors： Aoyama A,Katayama R,Oh-Hara T,Sato S,Okuno Y,Fujita N

更新日期：2014-12-01 00:00:00

abstract：:Several caged Garcinia xanthone natural products have potent bioactivity and a documented value in traditional Eastern medicine. Previous synthesis and structure activity relationship studies of these natural products resulted in the identification of the pharmacophore represented by the structure of cluvenone. In the...

journal_title：Molecular cancer therapeutics

authors： Batova A,Altomare D,Chantarasriwong O,Ohlsen KL,Creek KE,Lin YC,Messersmith A,Yu AL,Yu J,Theodorakis EA

更新日期：2010-11-01 00:00:00

abstract：:The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is known to play a role in sensitivity to temozolomide. Promoter hypermethylation of MGMT is commonly used to predict low expression levels of MGMT in gliomas, despite observed discordance between promoter methylation and protein levels. Here, we i...

journal_title：Molecular cancer therapeutics

authors： Moen EL,Stark AL,Zhang W,Dolan ME,Godley LA

更新日期：2014-05-01 00:00:00

abstract：:Histone modification has emerged as a promising approach to cancer therapy. We explored the efficacy of a novel class of histone deacetylase inhibitors in the treatment of malignant gliomas. Treatment of glioma cell lines with two butyric acid derivatives, pivaloylomethyl butyrate (AN-9) and butyroyloxymethyl butyrate...

journal_title：Molecular cancer therapeutics

authors： Entin-Meer M,Rephaeli A,Yang X,Nudelman A,VandenBerg SR,Haas-Kogan DA

更新日期：2005-12-01 00:00:00

abstract：:Although both erlotinib and gefitinib target the EGF receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective ...

journal_title：Molecular cancer therapeutics

authors： Augustin A,Lamerz J,Meistermann H,Golling S,Scheiblich S,Hermann JC,Duchateau-Nguyen G,Tzouros M,Avila DW,Langen H,Essioux L,Klughammer B

更新日期：2013-04-01 00:00:00

abstract：:Epidermal growth factor receptor (EGFR) vIII is a mutated EGFR that is frequently overexpressed in glioblastomas and implicated in response to receptor tyrosine kinase inhibitors. In this study, we investigate the effect of ZD6474 (ZACTIMA, vandetanib), a dual inhibitor for vascular endothelial growth factor receptor ...

journal_title：Molecular cancer therapeutics

authors： Yiin JJ,Hu B,Schornack PA,Sengar RS,Liu KW,Feng H,Lieberman FS,Chiou SH,Sarkaria JN,Wiener EC,Ma HI,Cheng SY

更新日期：2010-04-01 00:00:00

abstract：:Cationic liposomes have been used for targeted drug delivery to tumor blood vessels, via mechanisms that are not fully elucidated. Doxorubicin (Dox)-loaded liposomes were prepared that incorporate a cationic lipid; 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), along with a small amount of porphyrin-phospholipid (P...

journal_title：Molecular cancer therapeutics

authors： Luo D,Geng J,Li N,Carter KA,Shao S,Atilla-Gokcumen GE,Lovell JF

更新日期：2017-11-01 00:00:00

abstract：:There is an urgent need for the development of novel therapies to treat pancreatic cancer, which is among the most lethal of all cancers. KRAS-activating mutations, which are found in more than 90% of pancreatic adenocarcinomas, drive tumor dependency on the Ras/MAPK and Akt signaling pathways. Radiation is currently ...

journal_title：Molecular cancer therapeutics

authors： Williams TM,Flecha AR,Keller P,Ram A,Karnak D,Galbán S,Galbán CJ,Ross BD,Lawrence TS,Rehemtulla A,Sebolt-Leopold J

更新日期：2012-05-01 00:00:00