Development of cell-cycle inhibitors for cancer therapy Journal Article
| Authors: | Dickson, M. A.; Schwartz, G. K. |
| Article Title: | Development of cell-cycle inhibitors for cancer therapy |
| Abstract: | The cell cycle governs the transition from quiescence through cell growth to proliferation. The key parts of the cell cycle machinery are the cyclin-dependent kinases (CDKS) and the regulatory proteins called cyclins. The CDKS are rational targets for cancer therapy because their expression in cancer cells is often aberrant and their inhibition can induce cell death. Inhibitors of CDKS can also block transcription. Several drugs targeting the cell cycle have entered clinical trials. These agents include flavopiridol, indisulam, AZD5438, SNS-032, bryostatin-1, seliciclib, PD 0332991, and SCH 727965. Phase I studies have demonstrated that these drugs can generally be administered safely. Phase II studies have shown little single-agent activity in solid tumors, but combination studies with cytotoxic chemotherapy have been more promising. In hematologic malignancies, reports have shown encouraging single-agent and combination activity. Pharmacodynamic studies show that the dose and schedule of these drugs are crucial to permit maximum therapeutic effect. Copyright © 2009 Multimed Inc. |
| Keywords: | cancer chemotherapy; cancer survival; treatment response; unclassified drug; fludarabine; clinical trial; drug tolerability; fatigue; neutropenia; review; cisplatin; advanced cancer; diarrhea; drug dose reduction; drug efficacy; drug safety; recommended drug dose; side effect; solid tumor; drug targeting; capecitabine; gemcitabine; paclitaxel; drug megadose; antineoplastic agent; endometrium carcinoma; anorexia; cell proliferation; cell cycle; carboplatin; low drug dose; melanoma; progression free survival; apoptosis; drug eruption; infection; multiple cycle treatment; multiple myeloma; ovary cancer; breast cancer; anemia; bone marrow suppression; lung non small cell cancer; nausea; stomatitis; thrombocytopenia; myalgia; continuous infusion; drug design; docetaxel; irinotecan; asthenia; tumor lysis syndrome; cancer inhibition; chemotherapy induced emesis; hypokalemia; survival time; b cell lymphoma; hematologic malignancy; nonhodgkin lymphoma; colon cancer; lymphoma; single drug dose; checkpoint kinase 2; flavopiridol; esophagus cancer; hand foot syndrome; cyclin-dependent kinases; cyclins; phase i clinical trials; phase ii clinical trials; 6 acetyl 8 cyclopentyl 5 methyl 2 [5 (1 piperazinyl) 2 pyridinylamino] 8h pyrido[2,3 d]pyrimidin 7 one; azd 5438; bryostatin 1; checkpoint kinase 1; cyclin a; cyclin b; cyclin dependent kinase; cyclin dependent kinase inhibitor; indisulam; n [5 (5 tert butyl 2 oxazolylmethylthio) 2 thiazolyl]isonipecotamide; roscovitine; sch 727965; cell cycle phase; cell cycle regulation; chronic lymphatic leukemia; esophageal adenocarcinoma; lethargy; stomach adenocarcinoma; uterus cancer |
| Journal Title: | Current Oncology |
| Volume: | 16 |
| Issue: | 2 |
| ISSN: | 1198-0052 |
| Publisher: | Multimed Inc |
| Date Published: | 2009-03-01 |
| Start Page: | 36 |
| End Page: | 43 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC2669234 |
| PUBMED: | 19370178 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "CODEN: CUONF" - "Source: Scopus" |
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