CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin.
Simone Di Franco,Barbara Parrino,Miriam Gaggianesi,Vincenzo Davide Pantina,Paola Bianca,Annalisa Nicotra,Laura Rosa Mangiapane,Melania Lo Iacono,Gloria Ganduscio,Veronica Veschi,Ornella Roberta Brancato,Antonino Glaviano,Alice Turdo,Irene Pillitteri,Lorenzo Colarossi,Stella Cascioferro,Daniela Carbone,Camilla Pecoraro,Micol E. Fiori,Ruggero De Maria,Matilde Todaro,Isabella Screpanti,Girolamo Cirrincione,Patrizia Diana,Giorgio Stassi +24 more
Reads0
Chats0
TLDR
In this paper, the authors reported that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells, followed by an adaptive response selecting the CR-CSphC-resistant compartment.About:
This article is published in iScience.The article was published on 2021-05-29 and is currently open access. It has received 25 citations till now. The article focuses on the topics: Wnt signaling pathway & Stem cell.read more
Citations
More filters
Journal ArticleDOI
Metabolomics-assisted discovery of a new anticancer GLS-1 inhibitor chemotype from a nortopsentin-inspired library: From phenotype screening to target identification.
Daniela Carbone,Vincenzo Vestuto,Mariarosaria Ferraro,Tania Mara Ciaglia,Camilla Pecoraro,Eduardo Sommella,Stella Cascioferro,Emanuela Salviati,Sara Novi,Mario Felice Tecce,Giuseppina Amodio,Nunzio Iraci,Girolamo Cirrincione,Pietro Campiglia,Patrizia Diana,Alessia Bertamino,Barbara Parrino,Carmine Ostacolo +17 more
TL;DR: In this paper , the enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression and exacerbation of different aggressive tumors such as glioblastoma, hepatocarcinoma, pancreas, bone, and triple-negative breast cancer.
Journal ArticleDOI
Oxadiazole: A highly versatile scaffold in drug discovery
Nisheeth C. Desai,Jahnvi D. Monapara,Aratiba M. Jethawa,Vijay M. Khedkar,Bapurao B. Shingate +4 more
TL;DR: The present review will guide the way for researchers in the field of medicinal chemistry to design new biologically active molecules based on the oxadiazole nucleus.
Journal ArticleDOI
Messing Up the Cancer Stem Cell Chemoresistance Mechanisms Supported by Tumor Microenvironment.
Miriam Gaggianesi,Simone Di Franco,Vincenzo Davide Pantina,Gaetana Porcelli,Caterina D’Accardo,Francesco Verona,Veronica Veschi,Lorenzo Colarossi,Naida Faldetta,Giuseppe Pistone,Maria Rita Bongiorno,Matilde Todaro,Giorgio Stassi +12 more
TL;DR: In this paper, a combinatorial approach was proposed to perturb the interaction network between CSCs and the different component of TME, which strengthened CSC refractoriness to standard and targeted therapies by enhancing survival signaling pathways, DNA repair machinery, expression of drug efflux transporters and anti-apoptotic proteins.
Journal ArticleDOI
Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.
Jacqueline Nathansen,Felix Meyer,Luise K. Müller,Marc Schmitz,Kerstin Borgmann,Anna Dubrovska +5 more
TL;DR: A review of the role of DNA repair proteins in CSC maintenance and their potential as therapeutic targets can be found in this article, where the authors discuss the different roles of DNA Repair proteins in cancer stem cells.
Journal ArticleDOI
CHK1 protects oncogenic KRAS-expressing cells from DNA damage and is a target for pancreatic cancer treatment.
Jennifer E. Klomp,Ye S. Lee,Craig M. Goodwin,Björn Papke,Jeff Klomp,Adele Waters,Clint A. Stalnecker,Jonathan M. DeLiberty,Kristina Drizyte-Miller,Runying Yang,J. Nathaniel Diehl,Hongwei H. Yin,Mariaelena Pierobon,Elisa Baldelli,Meagan B. Ryan,Siqi Li,Jackson Peterson,Amber R. Smith,James T. Neal,Aaron K. McCormick,Calvin J. Kuo,Christopher M. Counter,Emanuel F. Petricoin,Adrienne D. Cox,Kirsten L. Bryant,Channing J. Der +25 more
TL;DR: In this paper, the authors apply genetic screens to delineate modulators of KRAS mutant pancreatic ductal adenocarcinoma (PDAC) sensitivity to ERK inhibitor treatment and identify components of the ATR-CHK1 DNA damage repair (DDR) pathway.
References
More filters
Journal ArticleDOI
Chk1 C-terminal regulatory phosphorylation mediates checkpoint activation by de-repression of Chk1 catalytic activity.
TL;DR: It is shown that Chk1 kinase activity is rapidly stimulated in a cell-cycle phase-specific manner in response to both DNA damage and replication arrest, and that the extent and duration of activation correlates closely with regulatory phosphorylation at serines (S) S317, S345 and S366.
Journal ArticleDOI
Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism.
Alessia Lodi,Achinto Saha,Xiyuan Lu,Bo Wang,Enrique Sentandreu,Meghan Collins,Mikhail G. Kolonin,John DiGiovanni,Stefano Tiziani +8 more
TL;DR: High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer, and ursolic acid and curcumin were identified as the most promising combination for inhibiting tumor growth.
Journal ArticleDOI
CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells
Gwenola Manic,Michele Signore,Antonella Sistigu,Giorgio Russo,Francesca Corradi,Silvia Siteni,Martina Musella,Sara Vitale,Maria Laura De Angelis,Matteo Pallocca,Carla Azzurra Amoreo,Francesca Sperati,Simone Di Franco,Sabina Barresi,Eleonora Policicchio,Eleonora Policicchio,Gabriele De Luca,Francesca De Nicola,Marcella Mottolese,Ann Zeuner,Maurizio Fanciulli,Giorgio Stassi,Marcello Maugeri-Saccà,Marta Baiocchi,Marco Tartaglia,Ilio Vitale,Ruggero De Maria +26 more
TL;DR: Results provide a strong rationale for biomarker-driven clinical trials with LY2606368 in patients with CRC, which selectively eliminates replication-stressed, p53-deficient and hyperdiploid CRC-SCs independently of RAS mutational status.
Journal ArticleDOI
Synthesis and in-vitro anticancer activity of 3,5-bis(indolyl)-1,2,4-thiadiazoles.
TL;DR: A series of 3,5-bis(indolyl)-1,2,4-thiadiazoles were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines and the compound 4h with 4-chlorobenzyl and methoxy substituents showed the most potent activity.
Journal ArticleDOI
Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma.
David S. Hong,Kathleen N. Moore,Kathleen N. Moore,Manish R. Patel,Stefan C. Grant,Howard A. Burris,William N. William,Suzanne F. Jones,Funda Meric-Bernstam,Jeffrey R. Infante,Lisa Golden,Wei Zhang,Ricardo Martinez,Sameera R. Wijayawardana,Richard P. Beckmann,Aimee Bence Lin,Cathy Eng,Johanna C. Bendell +17 more
TL;DR: The prexasertib maximum-tolerated dose of 105 mg/m2 was confirmed as the recommended phase II dose and demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC.