Targeting checkpoint kinase 1 in cancer therapeutics Journal Article
| Authors: | Tse, A. N.; Carvajal, R.; Schwartz, G. K. |
| Article Title: | Targeting checkpoint kinase 1 in cancer therapeutics |
| Abstract: | Progression through the cell cycle is monitored by surveillance mechanisms known as cell cycle checkpoints. Our knowledge of the biochemical nature of checkpoint regulation during an unperturbed cell cycle and following DNA damage has expanded tremendously over the past decade. We now know that dysfunction in cell cycle checkpoints leads to genomic instability and contributes to tumor progression, and most agents used for cancer therapy, such as cytotoxic chemotherapy and ionizing radiation, also activate cell cycle checkpoints. Understanding how checkpoints are regulated is therefore important from the points of view of both tumorigenesis and cancer treatment. In this review, we present an overview of the molecular hierarchy of the checkpoint signaling network and the emerging role of checkpoint targets, especially checkpoint kinase 1, in cancer therapy. Further, we discuss the results of recent clinical trials involving the nonspecific checkpoint kinase 1 inhibitor, UCN-01, and the challenges we face with this new therapeutic approach. ©2007 American Association for Cancer Research. |
| Keywords: | signal transduction; protein phosphorylation; unclassified drug; acute granulocytic leukemia; clinical trial; review; cisplatin; cytotoxic agent; doxorubicin; fluorouracil; cancer growth; drug potentiation; nonhuman; antineoplastic agents; drug targeting; gemcitabine; cytarabine; temozolomide; topotecan; antineoplastic agent; neoplasms; mitosis; protein analysis; animals; dna damage; cell cycle; low drug dose; bone marrow suppression; protein kinases; 7 ethyl 10 hydroxycamptothecin; antineoplastic activity; drug structure; protein p53; irinotecan; drug antagonism; drug distribution; drug mechanism; enzyme inhibitors; ionizing radiation; drug half life; dna topoisomerase inhibitor; mitomycin; checkpoint kinase 1; cell cycle phase; cell cycle regulation; drug protein binding; clinical trials; drug elimination; chemosensitization; caffeine; phase transition; 17 allylamino 17 demethoxygeldanamycin; 3 ethylidine 1,3 dihydroindol 2 one derivative; 7 hydroxystaurosporine; cep 3891; checkpoint kinase 1 blocking agent; chir 124; n aryl n' pyrazinylurea; pd 321852; pf 00394691 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 13 |
| Issue: | 7 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-04-01 |
| Start Page: | 1955 |
| End Page: | 1960 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-06-2793 |
| PUBMED: | 17404075 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 67" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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