bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 4 from Dihydroartemisinin Induces Apoptosis by a Bak-Dependent Intrinsic Pathway
Authors: Handrick René , Ontikatze Teona , Bauer Kerstin-Daniela , Freier Florian , Rübel Amelie , Dürig Jan , Belka Claus , Jendrossek Verena
Published: April 2023

Supplementary Figure 4 from Dihydroartemisinin Induces Apoptosis by a Bak-Dependent Intrinsic Pathway
Supplementary Figure 2 from Dihydroartemisinin Induces Apoptosis by a Bak-Dependent Intrinsic Pathway
Authors: Handrick René , Ontikatze Teona , Bauer Kerstin-Daniela , Freier Florian , Rübel Amelie , Dürig Jan , Belka Claus , Jendrossek Verena
Published: April 2023

Supplementary Figure 2 from Dihydroartemisinin Induces Apoptosis by a Bak-Dependent Intrinsic Pathway
Supplementary Fig. S4 from MEK/ERK inhibitor U0126 affects in vitro and in vivo growth of embryonal rhabdomyosarcoma
Authors: Marampon Francesco , Bossi Gianluca , Ciccarelli Carmela , Di Rocco Agnese , Sacchi Ada , Pestell Richard G. , Zani Bianca M.
Published: April 2023

Supplementary Fig. S4 from MEK/ERK inhibitor U0126 affects in vitro and in vivo growth of embryonal rhabdomyosarcoma
Supplementary Data from Estrogen-related receptor-α antagonist inhibits both estrogen receptor–positive and estrogen receptor–negative breast tumor growth in mouse xenografts
Authors: Chisamore Michael J. , Wilkinson Hilary A. , Flores Osvaldo , Chen J. Don
Published: April 2023

Supplementary Data from Estrogen-related receptor-α antagonist inhibits both estrogen receptor–positive and estrogen receptor–negative breast tumor growth in mouse xenografts
Supplementary Fig. S1 from Methyl-3-indolylacetate inhibits cancer cell invasion by targeting the MEK1/2-ERK1/2 signaling pathway
Authors: Zhang Siyuan , Li Zhi , Wu Ximei , Huang Qing , Shen Han-Ming , Ong Choon-Nam
Published: April 2023

Supplementary Fig. S1 from Methyl-3-indolylacetate inhibits cancer cell invasion by targeting the MEK1/2-ERK1/2 signaling pathway
Supplementary Figure Legends from MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance
Authors: Moriyama Taiki , Ohuchida Kenoki , Mizumoto Kazuhiro , Yu Jun , Sato Norihiro , Nabae Toshinaga , Takahata Shunichi , Toma Hiroki , Nagai Eishi , Tanaka Masao
Published: April 2023

Supplementary Figure Legends from MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance
Supplementary Data from A Novel Small-Molecule Inhibitor of Protein Kinase D Blocks Pancreatic Cancer Growth In vitro and In vivo
Authors: Harikumar Kuzhuvelil B. , Kunnumakkara Ajaikumar B. , Ochi Nobuo , Tong Zhimin , Deorukhkar Amit , Sung Bokyung , Kelland Lloyd , Jamieson Stephen , Sutherland Rachel , Raynham Tony , Charles Mark , Bagherzadeh Azadeh , Foxton Caroline , Boakes Alexandra , Farooq Muddasar , Maru Dipen , Diagaradjane Parmeswaran , Matsuo Yoichi , Sinnett-Smith James , Gelovani Juri , Krishnan Sunil , Aggarwal Bharat B. , Rozengurt Enrique , Ireson Christopher R. , Guha Sushovan
Published: April 2023

Supplementary Data from A Novel Small-Molecule Inhibitor of Protein Kinase D Blocks Pancreatic Cancer Growth In vitro and In vivo
Supplementary Fig. S1 from Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index
Authors: McDonagh Charlotte F. , Kim Kristine M. , Turcott Eileen , Brown Lindsay L. , Westendorf Lori , Feist Tiffany , Sussman Django , Stone Ivan , Anderson Martha , Miyamoto Jamie , Lyon Robert , Alley Stephen C. , Gerber Hans-Peter , Carter Paul J.
Published: April 2023

Supplementary Fig. S1 from Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index
Supplementary Figure 4 from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer
Authors: Sakai Ryo , Kagawa Shunsuke , Yamasaki Yasumoto , Kojima Toru , Uno Futoshi , Hashimoto Yuuri , Watanabe Yuichi , Urata Yasuo , Tanaka Noriaki , Fujiwara Toshiyoshi
Published: April 2023

Supplementary Figure 4 from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer
Supplementary Material from Mitogen-activated protein kinase kinase 1/2 inhibitors and 17-allylamino-17-demethoxygeldanamycin synergize to kill human gastrointestinal tumor cells in vitro via suppression of c-FLIP-s levels and activation of CD95
Authors: Park Margaret A. , Zhang Guo , Mitchell Clint , Rahmani Mohamed , Hamed Hossein , Hagan Michael P. , Yacoub Adly , Curiel David T. , Fisher Paul B. , Grant Steven , Dent Paul
Published: April 2023

Supplementary Material from Mitogen-activated protein kinase kinase 1/2 inhibitors and 17-allylamino-17-demethoxygeldanamycin synergize to kill human gastrointestinal tumor cells in vitro via suppression of c-FLIP-s levels and activation of CD95
Supplementary Table from A Human Monoclonal Antibody against Insulin-Like Growth Factor-II Blocks the Growth of Human Hepatocellular Carcinoma Cell Lines In vitro and In vivo
Authors: Dransfield Daniel T. , Cohen Edward H. , Chang Qing , Sparrow Lindsay G. , Bentley John D. , Dolezal Olan , Xiao Xiaowen , Peat Thomas S. , Newman Janet , Pilling Patricia A. , Phan Tram , Priebe Ilka , Brierley Gemma V. , Kastrapeli Niksa , Kopacz Kris , Martik Diana , Wassaf Dina , Rank Douglas , Conley Greg , Huang Yan , Adams Timothy E. , Cosgrove Leah
Published: April 2023

Supplementary Table from A Human Monoclonal Antibody against Insulin-Like Growth Factor-II Blocks the Growth of Human Hepatocellular Carcinoma Cell Lines In vitro and In vivo
Supplementary Appendix from Gene Expression Signatures as a Guide to Treatment Strategies for In-Transit Metastatic Melanoma
Authors: Augustine Christina K. , Jung Sin-Ho , Sohn Insuk , Yoo Jin Soo , Yoshimoto Yasunori , Olson John A. , Friedman Henry S. , Ali-Osman Francis , Tyler Douglas S.
Published: April 2023

Supplementary Appendix from Gene Expression Signatures as a Guide to Treatment Strategies for In-Transit Metastatic Melanoma
Supplementary Tables and Figure Legends from Multigene Expression–Based Predictors for Sensitivity to Vorinostat and Velcade in Non–Small Cell Lung Cancer
Authors: Nagji Alykhan S. , Cho Sang-Hoon , Liu Yuan , Lee Jae K. , Jones David R.
Published: April 2023

Supplementary Tables and Figure Legends from Multigene Expression–Based Predictors for Sensitivity to Vorinostat and Velcade in Non–Small Cell Lung Cancer
Supplementary Fig. from The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression
Authors: Liu Xinyi , Abdelrahim Maen , Abudayyeh Ala , Lei Ping , Safe Stephen
Published: April 2023

Supplementary Fig. from The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression
Supplementary Data from Synthesis and characterization of a high-affinity αvβ6-specific ligand for in vitro and in vivo applications
Authors: Li Shunzi , McGuire Michael J. , Lin Mai , Liu Ying-Horng , Oyama Tsukasa , Sun Xiankai , Brown Kathlynn C.
Published: April 2023

Supplementary Data from Synthesis and characterization of a high-affinity αvβ6-specific ligand for in vitro and in vivo applications
Supplementary Tables from The antitumor properties of a nontoxic, nitric oxide–modified version of saquinavir are independent of Akt
Authors: Maksimovic-Ivanic Danijela , Mijatovic Sanja , Miljkovic Djordje , Harhaji-Trajkovic Ljubica , Timotijevic Gordana , Mojic Marija , Dabideen Darrin , Cheng Kai Fan , McCubrey James A. , Mangano Katia , Al-Abed Yousef , Libra Massimo , Garotta Gianni , Stosic-Grujicic Stanislava , Nicoletti Ferdinando
Published: April 2023

Supplementary Tables from The antitumor properties of a nontoxic, nitric oxide–modified version of saquinavir are independent of Akt
Supplementary Table S1 from Anticancer peptide CIGB-300 binds to nucleophosmin/B23, impairs its CK2-mediated phosphorylation, and leads to apoptosis through its nucleolar disassembly activity
Authors: Perera Yasser , Farina Hernán G. , Gil Jeovanis , Rodriguez Arielis , Benavent Fernando , Castellanos Lila , Gómez Roberto E. , Acevedo Boris E. , Alonso Daniel F. , Perea Silvio E.
Published: April 2023

Supplementary Table S1 from Anticancer peptide CIGB-300 binds to nucleophosmin/B23, impairs its CK2-mediated phosphorylation, and leads to apoptosis through its nucleolar disassembly activity
Supplementary Fig. S4 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer
Authors: Liu Dong , Kojima Toru , Ouchi Masaaki , Kuroda Shinji , Watanabe Yuichi , Hashimoto Yuuri , Onimatsu Hideki , Urata Yasuo , Fujiwara Toshiyoshi
Published: April 2023

Supplementary Fig. S4 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer
Supplementary Table 1 from Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells
Authors: Moiseeva Elena P. , Almeida Gabriela M. , Jones George D.D. , Manson Margaret M.
Published: April 2023

DOC file, 111KB, Effect of dietary phytochemicals on metastasis and apoptosis in primary tumors in animal models.
Supplementary Figure Legends from Targeted Inhibition of Src Kinase Signaling Attenuates Pancreatic Tumorigenesis
Authors: Nagaraj Nagathihalli S. , Smith J. Joshua , Revetta Frank , Washington M. Kay , Merchant Nipun B.
Published: April 2023

Supplementary Figure Legends from Targeted Inhibition of Src Kinase Signaling Attenuates Pancreatic Tumorigenesis
Supplementary Data from Organic Cation Transporters Modulate the Uptake and Cytotoxicity of Picoplatin, a Third-Generation Platinum Analogue
Authors: More Swati S. , Li Shuanglian , Yee Sook Wah , Chen Ligong , Xu Zhidong , Jablons David M. , Giacomini Kathleen M.
Published: April 2023

Supplementary Data from Organic Cation Transporters Modulate the Uptake and Cytotoxicity of Picoplatin, a Third-Generation Platinum Analogue
Supplementary Figure Legends 1-2 from Breast Cancer Resistance Protein and P-glycoprotein Limit Sorafenib Brain Accumulation
Authors: Lagas Jurjen S. , van Waterschoot Robert A.B. , Sparidans Rolf W. , Wagenaar Els , Beijnen Jos H. , Schinkel Alfred H.
Published: April 2023

Supplementary Figure Legends 1-2 from Breast Cancer Resistance Protein and P-glycoprotein Limit Sorafenib Brain Accumulation
Supplementary Fig. S1 from SHP and Sin3A expression are essential for adamantyl-substituted retinoid-related molecule–mediated nuclear factor-κB activation, c-Fos/c-Jun expression, and cellular apoptosis
Authors: Farhana Lulu , Dawson Marcia I. , Xu Liping , Dannenberg Jan-Hermen , Fontana Joseph A.
Published: April 2023

Supplementary Fig. S1 from SHP and Sin3A expression are essential for adamantyl-substituted retinoid-related molecule–mediated nuclear factor-κB activation, c-Fos/c-Jun expression, and cellular apoptosis
Supplementary Fig. S5 from A selective small-molecule nuclear factor-κB inhibitor from a high-throughput cell-based assay for “activator protein-1 hits”
Authors: Kang Moon-Il , Henrich Curtis J. , Bokesch Heidi R. , Gustafson Kirk R. , McMahon James B. , Baker Alyson R. , Young Matthew R. , Colburn Nancy H.
Published: April 2023

Supplementary Fig. S5 from A selective small-molecule nuclear factor-κB inhibitor from a high-throughput cell-based assay for “activator protein-1 hits”
Supplementary Data from A Synergistic Interaction between Lapatinib and Chemotherapy Agents in a Panel of Cell Lines Is Due to the Inhibition of the Efflux Pump BCRP
Authors: Perry Jackie , Ghazaly Essam , Kitromilidou Christiana , McGrowder Eva H. , Joel Simon , Powles Thomas
Published: April 2023

Supplementary Data from A Synergistic Interaction between Lapatinib and Chemotherapy Agents in a Panel of Cell Lines Is Due to the Inhibition of the Efflux Pump BCRP
Supplementary Fig. S3 from A selective small-molecule nuclear factor-κB inhibitor from a high-throughput cell-based assay for “activator protein-1 hits”
Authors: Kang Moon-Il , Henrich Curtis J. , Bokesch Heidi R. , Gustafson Kirk R. , McMahon James B. , Baker Alyson R. , Young Matthew R. , Colburn Nancy H.
Published: April 2023

Supplementary Fig. S3 from A selective small-molecule nuclear factor-κB inhibitor from a high-throughput cell-based assay for “activator protein-1 hits”
Supplementary Data from Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins
Authors: Wei Jun , Kitada Shinichi , Rega Michele F. , Emdadi Aras , Yuan Hongbin , Cellitti Jason , Stebbins John L. , Zhai Dayong , Sun Jiazhi , Yang Li , Dahl Russell , Zhang Ziming , Wu Bainan , Wang Si , Reed Tyler A. , Lawrence Nicholas , Sebti Said , Reed John C. , Pellecchia Maurizio
Published: April 2023

Supplementary Data from Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins
Supplementary Figure 1 from The farnesyltransferase inhibitor R115777 (tipifarnib) in combination with tamoxifen acts synergistically to inhibit MCF-7 breast cancer cell proliferation and cell cycle progression in vitro and in vivo
Authors: Martin Lesley-Ann , Head Julia E. , Pancholi Sunil , Salter Janine , Quinn Emma , Detre Simone , Kaye Stan , Howes Angela , Dowsett Mitch , Johnston Stephen R.D.
Published: April 2023

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Supplementary Fig. S4 from Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Authors: Valli Claudia , Paroni Gabriela , Di Francesco Angela Maria , Riccardi Riccardo , Tavecchio Michele , Erba Eugenio , Boldetti Andrea , Gianni' Maurizio , Fratelli Maddalena , Pisano Claudio , Merlini Lucio , Antoccia Antonio , Cenciarelli Chiara , Terao Mineko , Garattini Enrico
Published: April 2023

Supplementary Fig. S4 from Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Supplementary Fig. S2 from Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Authors: Valli Claudia , Paroni Gabriela , Di Francesco Angela Maria , Riccardi Riccardo , Tavecchio Michele , Erba Eugenio , Boldetti Andrea , Gianni' Maurizio , Fratelli Maddalena , Pisano Claudio , Merlini Lucio , Antoccia Antonio , Cenciarelli Chiara , Terao Mineko , Garattini Enrico
Published: April 2023

Supplementary Fig. S2 from Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Supplementary Fig. S1 from Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Authors: Valli Claudia , Paroni Gabriela , Di Francesco Angela Maria , Riccardi Riccardo , Tavecchio Michele , Erba Eugenio , Boldetti Andrea , Gianni' Maurizio , Fratelli Maddalena , Pisano Claudio , Merlini Lucio , Antoccia Antonio , Cenciarelli Chiara , Terao Mineko , Garattini Enrico
Published: April 2023

Supplementary Fig. S1 from Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Supplementary Table from Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage
Authors: Krynetskaia Natalia F. , Phadke Manali S. , Jadhav Sachin H. , Krynetskiy Evgeny Y.
Published: April 2023

Supplementary Table from Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage
Supplementary Fig. S4 from Recombinant, refolded tetrameric p53 and gonadotropin-releasing hormone-p53 slow proliferation and induce apoptosis in p53-deficient cancer cells
Authors: LaFevre-Bernt Michelle , Wu Shili , Lin Xinli
Published: April 2023

Supplementary Fig. S4 from Recombinant, refolded tetrameric p53 and gonadotropin-releasing hormone-p53 slow proliferation and induce apoptosis in p53-deficient cancer cells
Supplementary Fig. S2 from Silibinin inhibits translation initiation: implications for anticancer therapy
Authors: Lin Chen-Ju , Sukarieh Rami , Pelletier Jerry
Published: April 2023

Supplementary Fig. S2 from Silibinin inhibits translation initiation: implications for anticancer therapy
Supplementary Table S1 from KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo
Authors: Hassig Christian A. , Symons Kent T. , Guo Xin , Nguyen Phan-Manh , Annable Tami , Wash Paul L. , Payne Joseph E. , Jenkins David A. , Bonnefous Céline , Trotter Carol , Wang Yan , Anzola John V. , Milkova Elena L. , Hoffman Timothy Z. , Dozier Sara J. , Wiley Brandon M. , Saven Alan , Malecha James W. , Davis Robert L. , Muhammad Jerry , Shiau Andrew K. , Noble Stewart A. , Rao Tadimeti S. , Smith Nicholas D. , Hager Jeffrey H.
Published: April 2023

Supplementary Table S1 from KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo
Supplementary Video 2 from ENMD-1198, a New Analogue of 2-Methoxyestradiol, Displays Both Antiangiogenic and Vascular-Disrupting Properties
Authors: Pasquier Eddy , Sinnappan Snega , Munoz Marcia A. , Kavallaris Maria
Published: April 2023

Large File
Supplementary Figure 3 from Improved low molecular weight Myc-Max inhibitors
Authors: Wang Huabo , Hammoudeh Dalia I. , Follis Ariele Viacava , Reese Brian E. , Lazo John S. , Metallo Steven J. , Prochownik Edward V.
Published: April 2023

Supplementary Figure 3 from Improved low molecular weight Myc-Max inhibitors
Supplementary Figure 1 from Improved low molecular weight Myc-Max inhibitors
Authors: Wang Huabo , Hammoudeh Dalia I. , Follis Ariele Viacava , Reese Brian E. , Lazo John S. , Metallo Steven J. , Prochownik Edward V.
Published: April 2023

Supplementary Figure 1 from Improved low molecular weight Myc-Max inhibitors
Supplementary Table 2 from SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer
Authors: Novotny-Diermayr Veronica , Sangthongpitag Kanda , Hu Chang Yong , Wu Xiaofeng , Sausgruber Nina , Yeo Pauline , Greicius Gediminas , Pettersson Sven , Liang Ai Leng , Loh Yung Kiang , Bonday Zahid , Goh Kee Chuan , Hentze Hannes , Hart Stefan , Wang Haishan , Ethirajulu Kantharaj , Wood Jeanette Marjorie
Published: April 2023

Supplementary Table 2 from SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer
Supplementary Table 1 from SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer
Authors: Novotny-Diermayr Veronica , Sangthongpitag Kanda , Hu Chang Yong , Wu Xiaofeng , Sausgruber Nina , Yeo Pauline , Greicius Gediminas , Pettersson Sven , Liang Ai Leng , Loh Yung Kiang , Bonday Zahid , Goh Kee Chuan , Hentze Hannes , Hart Stefan , Wang Haishan , Ethirajulu Kantharaj , Wood Jeanette Marjorie
Published: April 2023

Supplementary Table 1 from SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer
Supplementary Figures and Materials and Metholds from SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer
Authors: Novotny-Diermayr Veronica , Sangthongpitag Kanda , Hu Chang Yong , Wu Xiaofeng , Sausgruber Nina , Yeo Pauline , Greicius Gediminas , Pettersson Sven , Liang Ai Leng , Loh Yung Kiang , Bonday Zahid , Goh Kee Chuan , Hentze Hannes , Hart Stefan , Wang Haishan , Ethirajulu Kantharaj , Wood Jeanette Marjorie
Published: April 2023

Supplementary Figures and Materials and Metholds from SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer
Supplementary Fig. S4B from Antitumor activity of a membrane lytic peptide cyclized with a linker sensitive to membrane type 1-matrix metalloproteinase
Authors: Zhong Jieying , Chau Ying
Published: April 2023

Supplementary Fig. S4B from Antitumor activity of a membrane lytic peptide cyclized with a linker sensitive to membrane type 1-matrix metalloproteinase
Supplementary Tables 1-2 from Biochemical Characterization of AMG 102: A Neutralizing, Fully Human Monoclonal Antibody to Human and Nonhuman Primate Hepatocyte Growth Factor
Authors: Burgess Teresa L. , Sun Jan , Meyer Susanne , Tsuruda Trace S. , Sun Jilin , Elliott Gary , Chen Qing , Haniu Mitsuru , Barron Will F. , Juan Todd , Zhang Ke , Coxon Angela , Kendall Richard L.
Published: April 2023

Supplementary Tables 1-2 from Biochemical Characterization of AMG 102: A Neutralizing, Fully Human Monoclonal Antibody to Human and Nonhuman Primate Hepatocyte Growth Factor
Supplementary Table 1 from The Preclinical Pharmacology and Therapeutic Activity of the Novel CHK1 Inhibitor SAR-020106
Authors: Walton Michael I. , Eve Paul D. , Hayes Angela , Valenti Melanie , De Haven Brandon Alexis , Box Gary , Boxall Kathy J. , Aherne G. Wynne , Eccles Suzanne A. , Raynaud Florence I. , Williams David H. , Reader John C. , Collins Ian , Garrett Michelle D.
Published: April 2023

PDF file, 63KB, Kinase inhibitory profile of SAR-020106 at 10 μMa.
Supplementary Figure Legend from Biochemical Characterization of AMG 102: A Neutralizing, Fully Human Monoclonal Antibody to Human and Nonhuman Primate Hepatocyte Growth Factor
Authors: Burgess Teresa L. , Sun Jan , Meyer Susanne , Tsuruda Trace S. , Sun Jilin , Elliott Gary , Chen Qing , Haniu Mitsuru , Barron Will F. , Juan Todd , Zhang Ke , Coxon Angela , Kendall Richard L.
Published: April 2023

Supplementary Figure Legend from Biochemical Characterization of AMG 102: A Neutralizing, Fully Human Monoclonal Antibody to Human and Nonhuman Primate Hepatocyte Growth Factor
Supplementary Figure 1 from Biochemical Characterization of AMG 102: A Neutralizing, Fully Human Monoclonal Antibody to Human and Nonhuman Primate Hepatocyte Growth Factor
Authors: Burgess Teresa L. , Sun Jan , Meyer Susanne , Tsuruda Trace S. , Sun Jilin , Elliott Gary , Chen Qing , Haniu Mitsuru , Barron Will F. , Juan Todd , Zhang Ke , Coxon Angela , Kendall Richard L.
Published: April 2023

Supplementary Figure 1 from Biochemical Characterization of AMG 102: A Neutralizing, Fully Human Monoclonal Antibody to Human and Nonhuman Primate Hepatocyte Growth Factor
Supplementary Figure 4 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Authors: Ballot Caroline , Kluza Jérome , Martoriati Alain , Nyman Ulrika , Formstecher Pierre , Joseph Bertrand , Bailly Christian , Marchetti Philippe
Published: April 2023

Supplementary Figure 4 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Supplementary Figure 3 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Authors: Ballot Caroline , Kluza Jérome , Martoriati Alain , Nyman Ulrika , Formstecher Pierre , Joseph Bertrand , Bailly Christian , Marchetti Philippe
Published: April 2023

Supplementary Figure 3 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Supplementary Figure 2 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Authors: Ballot Caroline , Kluza Jérome , Martoriati Alain , Nyman Ulrika , Formstecher Pierre , Joseph Bertrand , Bailly Christian , Marchetti Philippe
Published: April 2023

Supplementary Figure 2 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Supplementary Data 7 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment
Authors: Ragusa Marco , Majorana Alessandra , Statello Luisa , Maugeri Marco , Salito Loredana , Barbagallo Davide , Guglielmino Maria Rosa , Duro Laura R. , Angelica Rosario , Caltabiano Rosario , Biondi Antonio , Di Vita Maria , Privitera Giuseppe , Scalia Marina , Cappellani Alessandro , Vasquez Enrico , Lanzafame Salvatore , Basile Francesco , Di Pietro Cinzia , Purrello Michele
Published: April 2023

Supplementary Data 7 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment
Supplementary Data 3 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment
Authors: Ragusa Marco , Majorana Alessandra , Statello Luisa , Maugeri Marco , Salito Loredana , Barbagallo Davide , Guglielmino Maria Rosa , Duro Laura R. , Angelica Rosario , Caltabiano Rosario , Biondi Antonio , Di Vita Maria , Privitera Giuseppe , Scalia Marina , Cappellani Alessandro , Vasquez Enrico , Lanzafame Salvatore , Basile Francesco , Di Pietro Cinzia , Purrello Michele
Published: April 2023

Supplementary Data 3 from Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment
Supplementary Figure 3 from Real-time Fluorescent Resonance Energy Transfer Analysis to Monitor Drug Resistance in Chronic Myelogenous Leukemia
Authors: Tunceroglu Ahmet , Matsuda Michiyuki , Birge Raymond B.
Published: April 2023

Supplementary Figure 3 from Real-time Fluorescent Resonance Energy Transfer Analysis to Monitor Drug Resistance in Chronic Myelogenous Leukemia
Supplementary Figure 1 from Real-time Fluorescent Resonance Energy Transfer Analysis to Monitor Drug Resistance in Chronic Myelogenous Leukemia
Authors: Tunceroglu Ahmet , Matsuda Michiyuki , Birge Raymond B.
Published: April 2023

This is a video file.
Data from Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides
Authors: de Wolf Cornelia , Jansen Robert , Yamaguchi Hiroaki , de Haas Marcel , van de Wetering Koen , Wijnholds Jan , Beijnen Jos , Borst Piet
Published: April 2023

Abstract
We have studied the potential contribution of ABCG2 (breast cancer resistance protein) to resistance to nucleoside analogues. In cells transfected with DNA constructs resulting in overexpression of human or mouse ABCG2, we found resistance against cladribine, clofarabine, fludarabine, 6-mercaptopurine, and 6-mercaptopurine riboside in both MDCKII and HEK293 cells and against gemcitabine only in HEK293 cells. With Transwell studies in MDCK cells and transport experiments with vesicles from Sf9 and HEK293 cells, we show that ABCG2 is able to transport not only the nucleotide CdAMP, like several other ATP-binding cassette transporters of the ABCC (multidrug resistance protein) family, but also the nucleoside cladribine itself. Expression of ABCG2 in cells results in a substantial decrease of intracellular CdATP, explaining the resistance against cladribine. The high transport rate of cladribine and clofarabine by ABCG2 deduced from Transwell experiments raises the possibility that this transporter could affect the disposition of nucleoside analogues in patients or cause resistance in tumors. [Mol Cancer Ther 2008;7(9):3092–102]
Data from Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival
Authors: Marcu Jahan P. , Christian Rigel T. , Lau Darryl , Zielinski Anne J. , Horowitz Maxx P. , Lee Jasmine , Pakdel Arash , Allison Juanita , Limbad Chandani , Moore Dan H. , Yount Garret L. , Desprez Pierre-Yves , McAllister Sean D.
Published: April 2023

Abstract
The cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor agonist Δ9-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 cannabinoids, which do not interact efficiently with CB1 and CB2 receptors, can modulate the actions of Δ9-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Δ9-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Δ9-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Δ9-THC. In the U251 and SF126 glioblastoma cell lines, Δ9-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients. Mol Cancer Ther; 9(1); 180–9
Data from Zinc Protoporphyrin IX Stimulates Tumor Immunity by Disrupting the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase
Authors: Metz Richard , DuHadaway James B. , Rust Sonja , Munn David H. , Muller Alexander J. , Mautino Mario , Prendergast George C.
Published: April 2023

Abstract
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) has emerged as an important driver of immune escape in a growing number of cancers and cancer-associated chronic infections. In this study, we define novel immunotherapeutic applications for the heme precursor compound zinc protoporphyrin IX (ZnPP) based on our discovery that it is a potent small-molecule inhibitor of IDO. Inhibitory activity was determined using in vitro and in-cell enzyme assays as well as a novel in vivo pharmacodynamic system. An irreversible mechanism of inhibition was documented, consistent with competition for heme binding in newly synthesized cellular protein. siRNA methodology and an IDO-deficient mouse strain were used to verify the specificity of ZnPP as an IDO inhibitor. In a preclinical model of melanoma, ZnPP displayed antitumor properties that relied on T-cell function and IDO integrity. ZnPP also phenocopied the known antitumor properties of IDO inhibitors in preclinical models of skin and breast carcinoma. Our results suggest clinical evaluation of ZnPP as an adjuvant immunochemotherapy in chronic infections and cancers in which there is emerging recognition of a pathophysiologic role for IDO dysregulation. Mol Cancer Ther; 9(6); 1864–71. ©2010 AACR.
Data from Monoclonal antibody 16D10 to the COOH-terminal domain of the feto-acinar pancreatic protein targets pancreatic neoplastic tissues
Authors: Benkoël Liliane , Bernard Jean-Paul , Payan-Defais Marie-José , Crescence Lydie , Franceschi Cécile , Delmas Mireille , Ouaissi Mehdi , Sastre Bernard , Sahel José , Benoliel Anne-Marie , Bongrand Pierre , Silvy Françoise , Gauthier Laurent , Romagné François , Lombardo Dominique , Mas Eric
Published: April 2023

Abstract
We have shown that the 16D10 antigen located on the mucin-like COOH-terminal domain of the feto-acinar pancreatic protein (FAPP) is expressed at the surface of human pancreatic tumor cell lines such as SOJ-6 cell line. Furthermore, an in vivo study indicates that targeting this cell-membrane glycopeptide by the use of the monoclonal antibody (mAb) 16D10 inhibits the growth of SOJ-6 xenografts in nude mice. To validate the potential use of the mAb16D10 in immune therapy, this study examined the expression of 16D10 antigens at the surface of human pancreatic adenocarcinomas versus control tissues. We examined the reactivity of mAb16D10 and mAb8H8 with pancreatic ductal adenocarcinomas (PDAC) compared with controls by using immunohistochemistry and confocal laser scanning microscopy. mAb8H8 does react with control or nontumoral human pancreatic tissues. mAb16D10 has a strong and specific reactivity with PDAC and does not react with other cancers of epithelia or normal tissues tested. Notable, mAb16D10 mostly recognizes membrane of tumoral cells. Furthermore, mAb8H8 and mAb16D10 recognized a protein of 110 to 120 kDa in homogenates of nontumoral and tumoral human pancreatic tissues, respectively. This size correlates with that of FAPP or with that of the normal counterpart of FAPP, the so-called bile salt-dependent lipase. The results suggest that mAb16D10 presents a unique specificity against PDAC; consequently, it could be effective in immune therapy of this cancer. Furthermore, mAb16D10 and mAb8H8 pair might be useful for diagnosis purpose in discriminating tumoral from nontumoral human pancreatic tissues. [Mol Cancer Ther 2009;8(2):282–91]
Data from Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib
Authors: Padera Timothy P. , Kuo Angera H. , Hoshida Tohru , Liao Shan , Lobo Jennifer , Kozak Kevin R. , Fukumura Dai , Jain Rakesh K.
Published: April 2023

Abstract
Blood vessels are required for a tumor to grow and functional lymphatic vessels are required for it to disseminate to lymph nodes. In an attempt to eradicate both the primary tumor and its lymphatic metastasis, we targeted both blood and lymphatic vessels using two different tyrosine kinase inhibitors (TKIs): cediranib and vandetanib, which block vascular endothelial growth factor receptor (VEGFR)-2 and -3 in enzymatic assays. We found that although both cediranib and vandetanib slowed the growth rate of primary tumors and reduced blood vessel density, neither agent was able to prevent lymphatic metastasis when given after tumor cells had seeded the lymph node. However, when given during tumor growth, cediranib reduced the diameters of the draining lymphatic vessels, the number of tumor cells arriving in the draining lymph node, and the incidence of lymphatic metastasis. On the other hand, vandetanib had minimal effect on any of these variables, suggesting that vandetanib did not effectively block VEGFR-3 on lymphatic endothelial cells in our animal model. Collectively, these data indicate that the response of lymphatic vessels to a TKI can determine the incidence of lymphatic metastasis, independent of the effect of the TKI on blood vessels. [Mol Cancer Ther 2008;7(8):2272–9]
Data from Silencing Kinase-Interacting Stathmin Gene Enhances Erlotinib Sensitivity by Inhibiting Ser10 p27 Phosphorylation in Epidermal Growth Factor Receptor–Expressing Breast Cancer
Authors: Zhang Dongwei , Tari Ana M. , Akar Ugur , Arun Banu K. , LaFortune Tiffany A. , Nieves-Alicea Rene , Hortobagyi Gabriel N. , Ueno Naoto T.
Published: April 2023

Abstract
The epidermal growth factor receptor (EGFR) signaling pathway has emerged as a promising target for cancer therapy. EGFR tyrosine kinase inhibitors (TKI) such as erlotinib have been approved for cancer treatment but have shown very limited activity in breast cancer patients. Clarifying the molecular mechanism underlying resistance to EGFR TKIs could lead to more effective treatment against breast cancer. We previously reported that the sensitivity of breast cancer cells to erlotinib is partially dependent on p27 and that cytoplasmic localization of p27 is associated with erlotinib resistance. In the present study, we found that erlotinib induces p27 phosphorylation at Ser10 (S10), and S10 p27 phosphorylation leads to erlotinib resistance in EGFR-expressing breast cancer. Inhibiting S10 phosphorylation of p27 by knocking down human kinase-interacting stathmin (KIS), a nuclear protein that can phosphorylate p27 at S10, led to p27 accumulation in the nucleus and enhanced erlotinib-mediated cytotoxicity. Further, in vivo KIS gene silencing enhanced the antitumor activity of erlotinib in an orthotopic breast cancer xenograft model. KIS depletion also enhanced erlotinib sensitivity in erlotinib-resistant EGFR-expressing triple-negative breast cancer cells. Our study provides a rationale for the development of combinations of erlotinib with KIS inhibition to overcome EGFR TKI resistance in EGFR-expressing breast cancer. Mol Cancer Ther; 9(11); 3090–9. ©2010 AACR.
Data from Anticancer peptide CIGB-300 binds to nucleophosmin/B23, impairs its CK2-mediated phosphorylation, and leads to apoptosis through its nucleolar disassembly activity
Authors: Perera Yasser , Farina Hernán G. , Gil Jeovanis , Rodriguez Arielis , Benavent Fernando , Castellanos Lila , Gómez Roberto E. , Acevedo Boris E. , Alonso Daniel F. , Perea Silvio E.
Published: April 2023

Abstract
CIGB-300, formerly known as P15-tat, is a proapoptotic peptide with established antiproliferative activity in vitro and antitumoral activity in vivo. This hypothesis-driven peptide was initially selected for its ability to impair the in vitro CK2-mediated phosphorylation in one of its substrates through direct binding to the conserved acidic phosphoaceptor domain. However, the actual in vivo target(s) on human cancer cells among the hundreds of CK2 substrates as well as the subsequent events that lead to apoptosis on tumor cells remains to be determined. In this work, we identified the multifunctional oncoprotein nucleophosmin/B23 as a major target for CIGB-300. In vivo, the CIGB-300–B23 interaction was shown by pull-down experiments and confirmed by the early in situ colocalization of both molecules in the cell nucleolus. Moreover, CIGB-300 inhibits the CK2-mediated phosphorylation of B23 in a dose-dependent fashion both in vitro and in vivo as shown using the recombinant GST fusion protein and the metabolic labeling approach, respectively. Such phosphorylation impairment was correlated with the ability of CIGB-300 to induce nucleolar disassembly as documented by the use of established markers for nucleolar structure. Finally, we showed that such a sequence of events leads to the rapid and massive onset of apoptosis both at the molecular and cellular levels. Collectively, these findings provide important clues by which the CIGB-300 peptide exerts its proapoptotic effect on tumor cells and highlights the suitability of the B23/CK2 pathway for cancer-targeted therapy. [Mol Cancer Ther 2009;8(5):OF1–8]
Data from Enhanced Anticancer Effect of the Combination of BIBW2992 and Thymidylate Synthase–Targeted Agents in Non–Small Cell Lung Cancer with the T790M Mutation of Epidermal Growth Factor Receptor
Authors: Takezawa Ken , Okamoto Isamu , Tanizaki Junko , Kuwata Kiyoko , Yamaguchi Haruka , Fukuoka Masahiro , Nishio Kazuto , Nakagawa Kazuhiko
Published: April 2023

Abstract
Most non–small cell lung cancer (NSCLC) tumors with activating mutations of the epidermal growth factor receptor (EGFR) are initially responsive to first-generation, reversible EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, but they subsequently develop resistance to these drugs through either acquisition of an additional T790M mutation of EGFR or amplification of the proto-oncogene MET. We have now investigated the effects of combination treatment with thymidylate synthase (TS)–targeting drugs and the second-generation, irreversible EGFR-TKI BIBW2992 on the growth of NSCLC cells with the T790M mutation. The effects of BIBW2992 on EGFR signaling and TS expression in gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of BIBW2992 and the TS-targeting agents S-1 (or 5-fluorouracil) or pemetrexed on the growth of gefitinib-resistant NSCLC cells were examined both in vitro and in vivo. The combination of BIBW2992 with 5-fluorouracil or pemetrexed synergistically inhibited the proliferation of NSCLC cells with the T790M mutation in vitro, whereas an antagonistic interaction was apparent in this regard between gefitinib and either of these TS-targeting agents. BIBW2992 induced downregulation of TS in the gefitinib-resistant NSCLC cells, implicating depletion of TS in the enhanced antitumor effect of the combination therapy. The combination of BIBW2992 and either the oral fluoropyrimidine S-1 or pemetrexed also inhibited the growth of NSCLC xenografts with the T790M mutation to an extent greater than that apparent with either agent alone. The addition of TS-targeting drugs to BIBW2992 is a promising strategy to overcome EGFR-TKI resistance in NSCLC with the T790M mutation of EGFR. Mol Cancer Ther; 9(6); 1647–56. ©2010 AACR.
Data from Cell surface profiling with peptide libraries yields ligand arrays that classify breast tumor subtypes
Authors: Dane Karen Y. , Gottstein Claudia , Daugherty Patrick S.
Published: April 2023

Abstract
Cancer heterogeneity renders risk stratification and therapy decisions challenging. Thus, genomic and proteomic methodologies have been used in an effort to identify biomarkers that can differentiate tumor subtypes to improve therapeutic outcome. Here, we report a generally applicable strategy to generate tumor type–specific peptide ligand arrays. Peptides that specifically recognize breast tumor-derived cell lines (MDA-MB-231, MCF-7, and T47-D) were identified using cell-displayed peptide libraries carrying an intrinsic fluorescent marker allowing for sorting and characterization with quantitative flow cytometry. Tumor cell specificity was achieved by depleting libraries of ligands binding to normal mammary epithelial cells (HMEC and MCF-10A). Although integrin binding RGD motifs were favored by some cell lines, screening with RGD competitors yielded several novel consensus motifs exhibiting improved tumor specificity. The resultant peptide array contained multiple consensus motifs exhibiting strong similarity to breast tumor–associated proteins. Profiling a panel of breast cancer cell lines with the peptide array revealed receptor expression patterns distinctive for luminal or basal tumor subtypes. In addition, peptide displaying bacteria and peptide functionalized microparticles enabled fluorescent labeling of tumor cells and frozen tumor tissue sections. Our results indicate that cell surface profiling using highly specific breast tumor cell binding ligands may provide an efficient route for tumor subtype classification, biomarker identification, and for the development of targeted diagnostics and therapeutics. [Mol Cancer Ther 2009;8(5):1312–8]
Data from Recombinant, refolded tetrameric p53 and gonadotropin-releasing hormone-p53 slow proliferation and induce apoptosis in p53-deficient cancer cells
Authors: LaFevre-Bernt Michelle , Wu Shili , Lin Xinli
Published: April 2023

Abstract
The p53 tumor suppressor is mutated in over 50% of human cancers. Mutations resulting in amino acid changes within p53 result in a loss of activity and consequent changes in expression of genes that regulate DNA repair and cell cycle progression. Replacement of p53 using protein therapy would restore p53 function in p53-deficient tumor cells, with a consequence of tumor cell death and tumor regression. p53 functions in a tetrameric form in vivo. Here, we refolded a wild-type, full-length p53 from inclusion bodies expressed in Escherichia coli as a stable tetramer. The tetrameric p53 binds to p53-specific DNA and, when transformed into a p53-deficient cancer cell line, induced apoptosis of the transformed cells. Next, using the same expression and refolding technology, we produced a stable tetramer of recombinant gonadotropin-releasing hormone-p53 fusion protein (GnRH-p53), which traverses the plasma membrane, slows proliferation, and induces apoptosis in p53-deficient, GnRH-receptor–expressing cancer cell lines. In addition, we showed a time-dependent binding and internalization of GnRH-p53 to a receptor-expressing cell line. We conclude that the GnRH-p53 fusion strategy may provide a basis for constructing an effective cancer therapeutic for patients with tumors in GnRH-receptor–positive tissue types. [Mol Cancer Ther 2008;7(6):1420–9]
Data from ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity
Authors: Munshi Neru , Jeay Sébastien , Li Youzhi , Chen Chang-Rung , France Dennis S. , Ashwell Mark A. , Hill Jason , Moussa Magdi M. , Leggett David S. , Li Chiang J.
Published: April 2023

Abstract
The met proto-oncogene is functionally linked with tumorigenesis and metastatic progression. Validation of the receptor tyrosine kinase c-Met as a selective anticancer target has awaited the emergence of selective c-Met inhibitors. Herein, we report ARQ 197 as the first non-ATP–competitive small molecule that selectively targets the c-Met receptor tyrosine kinase. Exposure to ARQ 197 resulted in the inhibition of proliferation of c-Met–expressing cancer cell lines as well as the induction of caspase-dependent apoptosis in cell lines with constitutive c-Met activity. These cellular responses to ARQ 197 were phenocopied by RNAi-mediated c-Met depletion and further demonstrated by the growth inhibition of human tumors following oral administration of ARQ 197 in multiple mouse xenograft efficacy studies. Cumulatively, these data suggest that ARQ 197, currently in phase II clinical trials, is a promising agent for targeting cancers in which c-Met-driven signaling is important for their survival and proliferation. Mol Cancer Ther; 9(6); 1544–53. ©2010 AACR.
Data from Transcriptional Analysis of an E2F Gene Signature as a Biomarker of Activity of the Cyclin-Dependent Kinase Inhibitor PHA-793887 in Tumor and Skin Biopsies from a Phase I Clinical Study
Authors: Locatelli Giuseppe , Bosotti Roberta , Ciomei Marina , Brasca Maria G. , Calogero Raffaele , Mercurio Ciro , Fiorentini Francesco , Bertolotti Matteo , Scacheri Emanuela , Scaburri Angela , Galvani Arturo , Pesenti Enrico , De Baere Thierry , Soria Jean-Charles , Lazar Vladimir , Isacchi Antonella
Published: April 2023

Abstract
A transcriptional signature of the pan–cyclin-dependent kinase (Cdk) inhibitor PHA-793887 was evaluated as a potential pharmacodynamic and/or response biomarker in tumor and skin biopsies from patients treated in a phase I clinical study. We first analyzed the expression of a number of known E2F-dependent genes that were predicted to be modulated after Cdk2 and Cdk4 inhibition in xenograft tumor and skin samples of mice treated with the compound. This panel of 58 selected genes was then analyzed in biopsies from seven patients treated with PHA-793887 in a phase I dose escalation clinical trial in solid tumors. Quantitative real-time PCR or microarray analyses were done in paired skin and tumor biopsies obtained at baseline and at cycle 1. Analysis by quantitative real-time PCR of the signature in skin biopsies of patients treated at three different doses showed significant transcriptional downregulation with a dose-response correlation. These data show that PHA-793887 modulates genes involved in cell cycle regulation and proliferation in a clinical setting. The observed changes are consistent with its mechanism of action and correlate with target modulation in skin and with clinical benefit in tumors. Mol Cancer Ther; 9(5); 1265–73. ©2010 AACR.