Targeting the cell cycle: A new approach to cancer therapy Journal Article
| Authors: | Schwartz, G. K.; Shah, M. A. |
| Article Title: | Targeting the cell cycle: A new approach to cancer therapy |
| Abstract: | The cell cycle represents a series of tightly integrated events that allow the cell to grow and proliferate. Critical parts of the cell cycle machinery are the cyclin-dependent kinases (CDKs), which, when activated, provide a means for the cell to move from one phase of the cell cycle to the next. The CDKs are regulated positively by cyclins and regulated negatively by naturally occurring CDK inhibitors (CDKIs). Cancer represents a dysregulation of the cell cycle such that cells that overexpress cyclins or do not express the CDKIs continue to undergo unregulated cell growth. The cell cycle also serves to protect the cell from DNA damage. Thus, cell cycle arrest, in fact, represents a survival mechanism that provides the tumor cell the opportunity to repair its own damaged DNA. Thus, abrogation of cell cycle checkpoints, before DNA repair is complete, can activate the apoptotic cascade, leading to cell death. Now in clinical trials are a series of targeted agents that directly inhibit the CDKs, inhibit unrestricted cell growth, and induce growth arrest. Recent attention has also focused on these drugs as inhibitors of transcription. In addition, there are now agents that abrogate the cell cycle checkpoints at critical time points that make the tumor cell susceptible to apoptosis. An understanding of the cell cycle is critical to understanding how best to clinically develop these agents, both as single agents and in combination with chemotherapy. © 2005 by American Society of Clinical Oncology. |
| Keywords: | unclassified drug; clinical trial; constipation; fatigue; neutropenia; review; sorafenib; cisplatin; doxorubicin; cancer combination chemotherapy; diarrhea; drug dose reduction; drug potentiation; liver function; monotherapy; nonhuman; recommended drug dose; side effect; antineoplastic agents; pathophysiology; gemcitabine; paclitaxel; cytarabine; antineoplastic agent; neoplasm; neoplasms; cell proliferation; mitosis; metabolism; dna damage; gene; cell cycle; dna repair; carboplatin; apoptosis; controlled clinical trial; lung toxicity; multiple cycle treatment; cell growth; randomized controlled trial; antineoplastic combined chemotherapy protocols; myalgia; combination chemotherapy; continuous infusion; drug structure; drug effect; cancer therapy; physiology; docetaxel; irinotecan; drug dose escalation; hyperglycemia; rash; hypokalemia; hypotension; lung metastasis; drug antagonism; head and neck cancer; polo like kinase 1; gefitinib; vorinostat; cell cycle arrest; nausea and vomiting; cell cycle m phase; flavopiridol; drug bioavailability; drug blood level; drug dose increase; oxaliplatin; cyclin-dependent kinases; bryostatin 1; cyclin dependent kinase; cyclin dependent kinase inhibitor; indisulam; n [5 (5 tert butyl 2 oxazolylmethylthio) 2 thiazolyl]isonipecotamide; roscovitine; cell cycle regulation; cell protection; cell cycle g0 phase; genes, cdc; aurora b kinase; aurora a kinase; on 01910; sb 743921; pd 0332991; 7 hydroxystaurosporine; ck 0106023; imidazopyridine derivative; pyrido[2,3 d]pyrimidine derivative |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 23 |
| Issue: | 36 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2005-12-20 |
| Start Page: | 9408 |
| End Page: | 9421 |
| Language: | English |
| DOI: | 10.1200/jco.2005.01.5594 |
| PUBMED: | 16361640 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 187" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus" |
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