Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers.


:Molecular profiling of markers involved in the activity of chemotherapeutic agents can shed light on the successes and failures of treatment in patients and can also provide a basis for individualization of therapy. Toward those ends, we have used reverse-phase protein lysate microarrays to evaluate expression of protein components of the nucleotide excision repair (NER) pathways. Those pathways strongly influence the anticancer activities of numerous drugs, including those that are the focus here, cisplatin and ecteinascidin 743 (Et-743; Yondelis, Trabectedin). Cisplatin is generally more active in cell types deficient in NER, whereas Et-743 tends to be less active in those cells. We measured protein expression and sensitivity to those drugs in 17 human ovarian and colon cancer cell lines (13 of them from the NCI-60 panel) and five xeroderma pigmentosum (XP) patient cell types, each containing a different NER defect. Of the NER proteins giving reliable signals, XPF and XPG showed the highest correlations of protein expression with drug activity across all three tissue-of-origin groups. When we compared protein expression data with mRNA expression data from Affymetrix U133A chips, we found no consistent correlation between the two across the cell lines studied, which reinforces the conclusion that protein measurements can give more interpretable mechanistic information than can transcript measurements. The work reported here provides motivation for larger proteomic studies with more cell types focused on potential biomarkers in additional pharmacologically pertinent pathways.


Mol Cancer Ther


Stevens EV,Nishizuka S,Antony S,Reimers M,Varma S,Young L,Munson PJ,Weinstein JN,Kohn EC,Pommier Y




Has Abstract


2008-01-01 00:00:00














  • Response prediction to a multitargeted kinase inhibitor in cancer cell lines and xenograft tumors using high-content tyrosine peptide arrays with a kinetic readout.

    abstract::Multitargeted kinase inhibitors have shown clinical efficacy in a range of cancer types. However, two major problems associated with these drugs are the low fraction of patients for which these treatments provide initial clinical benefit and the occurrence of resistance during prolonged therapy. Several types of predi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Versele M,Talloen W,Rockx C,Geerts T,Janssen B,Lavrijssen T,King P,Göhlmann HW,Page M,Perera T

    更新日期:2009-07-01 00:00:00

  • KD5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by DNA damage and mitochondrial signaling.

    abstract::Histone deacetylase inhibitors have emerged as promising anticancer drugs. Using an unbiased ultrahigh throughput screening system, a novel mercaptoketone-based histone deacetylase inhibitor series was identified that was optimized to the lead compound, KD5170. KD5170 inhibited the proliferation of myeloma cell lines ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Feng R,Ma H,Hassig CA,Payne JE,Smith ND,Mapara MY,Hager JH,Lentzsch S

    更新日期:2008-06-01 00:00:00

  • Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows.

    abstract::Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章,评审


    authors: Roberts PJ,Kumarasamy V,Witkiewicz AK,Knudsen ES

    更新日期:2020-08-01 00:00:00

  • An optical probe for noninvasive molecular imaging of orthotopic brain tumors overexpressing epidermal growth factor receptor.

    abstract::We have developed a near-infrared (NIR) probe that targets cells overexpressing the EGF receptor (EGFR) for imaging glioblastoma brain tumors in live subjects. A peptide specific for the EGFR was modified with various lengths of monodiscrete polyethylene glycol (PEG) units and a NIR Cy5.5 fluorescence dye. The lead co...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Agnes RS,Broome AM,Wang J,Verma A,Lavik K,Basilion JP

    更新日期:2012-10-01 00:00:00

  • Soluble type II transforming growth factor-beta receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expressio...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Rowland-Goldsmith MA,Maruyama H,Matsuda K,Idezawa T,Ralli M,Ralli S,Korc M

    更新日期:2002-01-01 00:00:00

  • Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer.

    abstract::Constitutively activated STAT3 and STAT5 are expressed in a wide variety of human malignancies including solid and hematopoietic cancers and often correlate with a poor prognosis and resistance to multiple therapies. Given the well established role of STAT3 in tumorigenesis, inhibition of Janus-activated kinase 2 (JAK...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Seavey MM,Lu LD,Stump KL,Wallace NH,Hockeimer W,O'Kane TM,Ruggeri BA,Dobrzanski P

    更新日期:2012-04-01 00:00:00

  • Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer.

    abstract::Our previous studies and those of others have indicated that X-linked inhibitor of apoptosis protein (XIAP) holds promise as a target gene in colon cancer gene therapy. In this study, we constructed an adenoviral vector to deliver small hairpin RNA (shRNA) against XIAP (XIAP-shRNA) into colon cancer cells and tested i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Dai Y,Qiao L,Chan KW,Yang M,Ye J,Zhang R,Ma J,Zou B,Lam CS,Wang J,Pang R,Tan VP,Lan HY,Wong BC

    更新日期:2009-09-01 00:00:00

  • MLN0128, an ATP-competitive mTOR kinase inhibitor with potent in vitro and in vivo antitumor activity, as potential therapy for bone and soft-tissue sarcoma.

    abstract::The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that exists in two complexes (mTORC1 and mTORC2) and integrates extracellular and intracellular signals to act as a master regulator of cell growth, survival, and metabolism. The PI3K/AKT/mTOR prosurvival pathway is often dysregulated in mul...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Slotkin EK,Patwardhan PP,Vasudeva SD,de Stanchina E,Tap WD,Schwartz GK

    更新日期:2015-02-01 00:00:00

  • Zoledronic acid inhibits osteosarcoma growth in an orthotopic model.

    abstract::Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. Its efficacy in osteosarcoma has not been convincingly proved in a clinically relevant model for the disease. In vitro, ZOL decreased osteosarcoma cell proliferation, mainly due to an increase in apoptosis in a dose-dependent fashion. There ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Dass CR,Choong PF

    更新日期:2007-12-01 00:00:00

  • Novel irreversible small molecule inhibitors of replication protein A display single-agent activity and synergize with cisplatin.

    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

    pub_type: 杂志文章


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

    更新日期:2011-10-01 00:00:00

  • A new nonestrogenic steroidal inhibitor of 17β-hydroxysteroid dehydrogenase type I blocks the estrogen-dependent breast cancer tumor growth induced by estrone.

    abstract::17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) converts estrone (E1) into estradiol (E2) and is expressed in many steroidogenic tissues and breast cancer cell lines. Because the potent estrogen E2 stimulates the growth and development of hormone-dependent diseases, inhibition of the final step of E2 synthesis is c...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Ayan D,Maltais R,Roy J,Poirier D

    更新日期:2012-10-01 00:00:00

  • Pharmacologic inhibition of CDC25 phosphatases impairs interphase microtubule dynamics and mitotic spindle assembly.

    abstract::The CDC25 cell cycle regulators are promising targets for new pharmacologic approaches in cancer therapy. Inhibitory compounds such as BN82685 have proven to be effective in specifically targeting CDC25 in cultured cells and in inhibiting tumor cell growth. Here, we report that BN82685 impairs microtubule dynamic inst...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Cazales M,Boutros R,Brezak MC,Chaumeron S,Prevost G,Ducommun B

    更新日期:2007-01-01 00:00:00

  • Vitamin E succinate induces NAG-1 expression in a p38 kinase-dependent mechanism.

    abstract::NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor-beta superfamily, is involved in many cellular processes, such as inflammation, apoptosis/survival, and tumorigenesis. Vitamin E succinate (VES) is the succinate derivative of alpha-tocopherol and has antitumorigenic...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Shim M,Eling TE

    更新日期:2008-04-01 00:00:00

  • 2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation.

    abstract::Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. Here, we found that hypersensitivity...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Kovács K,Decatur C,Toro M,Pham DG,Liu H,Jing Y,Murray TG,Lampidis TJ,Merchan JR

    更新日期:2016-02-01 00:00:00

  • The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice.

    abstract::CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy)-fused pyrrolocarbazole with potent pan-vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients. These studies evaluated the...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Jones-Bolin S,Zhao H,Hunter K,Klein-Szanto A,Ruggeri B

    更新日期:2006-07-01 00:00:00

  • GPR54 is a target for suppression of metastasis in endometrial cancer.

    abstract::Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, kisspeptin (KISS1), and i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Kang HS,Baba T,Mandai M,Matsumura N,Hamanishi J,Kharma B,Kondoh E,Yoshioka Y,Oishi S,Fujii N,Murphy SK,Konishi I

    更新日期:2011-04-01 00:00:00

  • Minicircle DNA-Engineered CAR T Cells Suppressed Tumor Growth in Mice.

    abstract::Viral-based chimeric antigen receptor-engineered T (CAR T)-cell manufacturing has potential safety risks and relatively high costs. The nonviral minicircle DNA (mcDNA) is safer for patients, cheaper to produce, and may be a more suitable technique to generate CAR T cells. In this study, we produced mcDNA-based CAR T c...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Han J,Gao F,Geng S,Ye X,Wang T,Du P,Cai Z,Fu Z,Zhao Z,Shi L,Li Q,Cai J

    更新日期:2020-01-01 00:00:00

  • A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types.

    abstract::Urokinase plasminogen activator (uPA) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. Due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. These have m...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Abi-Habib RJ,Singh R,Liu S,Bugge TH,Leppla SH,Frankel AE

    更新日期:2006-10-01 00:00:00

  • The Protein Tyrosine Phosphatase Activity of Eyes Absent Contributes to Tumor Angiogenesis and Tumor Growth.

    abstract::DNA damage repair capacity is required for cells to survive catastrophic DNA damage and proliferate under conditions of intratumoral stress. The ability of the minor histone protein H2AX to serve as a hub for the assembly of a productive DNA damage repair complex is a necessary step in preventing DNA damage-induced ce...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Wang Y,Pandey RN,Riffle S,Chintala H,Wikenheiser-Brokamp KA,Hegde RS

    更新日期:2018-08-01 00:00:00

  • Comparison of antitumor effects of multitargeted tyrosine kinase inhibitors in acute myelogenous leukemia.

    abstract::We compared the antitumor activities of the multitargeted tyrosine kinase inhibitors imatinib, sorafenib, and sunitinib to determine which inhibitor is best suited to be used for the treatment of acute myelogenous leukemia (AML). In nine human AML cell lines, sorafenib and sunitinib were more potent inhibitors of cell...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Hu S,Niu H,Minkin P,Orwick S,Shimada A,Inaba H,Dahl GV,Rubnitz J,Baker SD

    更新日期:2008-05-01 00:00:00

  • The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells.

    abstract::G-protein mutations are one of the most common mutations occurring in uveal melanoma activating the protein kinase C (PKC)/mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K)/AKT pathways. In this study, we described the effect of dual pathway inhibition in uveal melanoma harboring GNAQ and GNA11 mut...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Musi E,Ambrosini G,de Stanchina E,Schwartz GK

    更新日期:2014-05-01 00:00:00

  • RANKL-Targeted Combination Therapy with Osteoprotegerin Variant Devoid of TRAIL Binding Exerts Biphasic Effects on Skeletal Remodeling and Antitumor Immunity.

    abstract::Complexities in treating breast cancer with bone metastasis are enhanced by a vicious protumorigenic pathology, involving a shift in skeletal homeostasis toward aggressive osteoclast activity and polarization of immune cells supporting tumor growth and immunosuppression. Recent studies signify the role of receptor act...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Wang H,Ashton R,Hensel JA,Lee JH,Khattar V,Wang Y,Deshane JS,Ponnazhagan S

    更新日期:2020-12-01 00:00:00

  • Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2.

    abstract::The standard treatment for advanced, androgen-responsive prostate cancer is androgen deprivation therapy with or without a nonsteroidal antiandrogen, such as bicalutamide. Although maximal androgen blockade exhibits favorable responses in the majority of patients, prostate cancer eventually progresses to an androgen-r...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Feng S,Tang Q,Sun M,Chun JY,Evans CP,Gao AC

    更新日期:2009-03-01 00:00:00

  • TGFβ Blockade Enhances Radiotherapy Abscopal Efficacy Effects in Combination with Anti-PD1 and Anti-CD137 Immunostimulatory Monoclonal Antibodies.

    abstract::Radiotherapy can be synergistically combined with immunotherapy in mouse models, extending its efficacious effects outside of the irradiated field (abscopal effects). We previously reported that a regimen encompassing local radiotherapy in combination with anti-CD137 plus anti-PD-1 mAbs achieves potent abscopal effect...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Rodríguez-Ruiz ME,Rodríguez I,Mayorga L,Labiano T,Barbes B,Etxeberria I,Ponz-Sarvise M,Azpilikueta A,Bolaños E,Sanmamed MF,Berraondo P,Calvo FA,Barcelos-Hoff MH,Perez-Gracia JL,Melero I

    更新日期:2019-03-01 00:00:00

  • HMDB and 5-AzadC Combination Reverses Tumor Suppressor CCAAT/Enhancer-Binding Protein Delta to Strengthen the Death of Liver Cancer Cells.

    abstract::Hepatocellular carcinoma (HCC) can arise from chronic inflammation due to viral infection, organ damage, drug toxicity, or alcohol abuse. Moreover, gene desensitization via aberrant CpG island methylation is a frequent epigenetic defect in HCC. However, the details of how inflammation is linked with epigenetic-mediate...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Li CF,Tsai HH,Ko CY,Pan YC,Yen CJ,Lai HY,Yuh CH,Wu WC,Wang JM

    更新日期:2015-11-01 00:00:00

  • Targeted Inhibition of ULK1 Promotes Apoptosis and Suppresses Tumor Growth and Metastasis in Neuroblastoma.

    abstract::Neuroblastoma is the most common extracranial solid malignancy in the pediatric population, accounting for over 9% of all cancer-related deaths in children. Autophagy is a cell self-protective mechanism that promotes tumor cell growth and survival, making it an attractive target for treating cancer. However, the role ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Dower CM,Bhat N,Gebru MT,Chen L,Wills CA,Miller BA,Wang HG

    更新日期:2018-11-01 00:00:00

  • Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.

    abstract::Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. We therefore aimed to assess the frequency and distribution of CDK12 protein expression by IHC in i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Naidoo K,Wai PT,Maguire SL,Daley F,Haider S,Kriplani D,Campbell J,Mirza H,Grigoriadis A,Tutt A,Moseley PM,Abdel-Fatah TMA,Chan SYT,Madhusudan S,Rhaka EA,Ellis IO,Lord CJ,Yuan Y,Green AR,Natrajan R

    更新日期:2018-01-01 00:00:00

  • Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites.

    abstract::Mithramycin A is a DNA-binding antitumor agent, which has been clinically used in the therapies of several types of cancer and Paget's disease. In this study, we investigated the combined effect of mithramycin A and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) on apoptosis of cancer cells. In ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Lee TJ,Jung EM,Lee JT,Kim S,Park JW,Choi KS,Kwon TK

    更新日期:2006-11-01 00:00:00

  • Endothelin-2 is a hypoxia-induced autocrine survival factor for breast tumor cells.

    abstract::Endothelins (ETs) are a group of vasoactive peptides (ET-1, ET-2 and ET-3) produced by many cell types that bind to G-protein-linked transmembrane receptors, ET-A receptors (ET-RAs) and ET-B receptors (ET-RBs). These peptides are expressed in several human tumors, including carcinomas of the breast, and have a mitogen...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Grimshaw MJ,Naylor S,Balkwill FR

    更新日期:2002-12-01 00:00:00

  • Identification of biomarkers for tumor endothelial cell proliferation through gene expression profiling.

    abstract::Extensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cel...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Hardwick JS,Yang Y,Zhang C,Shi B,McFall R,Koury EJ,Hill SL,Dai H,Wasserman R,Phillips RL,Weinstein EJ,Kohl NE,Severino ME,Lamb JR,Sepp-Lorenzino L

    更新日期:2005-03-01 00:00:00