Clinical update: Novel targets in gynecologic malignancies Journal Article
| Author: | Aghajanian, C. |
| Article Title: | Clinical update: Novel targets in gynecologic malignancies |
| Abstract: | The proteasome inhibitor bortezomib has shown activity in chemotherapy-resistant tumors and is approved for treatment of multiple myeloma. The critical component of bortezomib's antitumor activity is the inhibition of nuclear factor-kappa B (NF-κB). Patients with ovarian cancer respond to initial platinum-based chemotherapy, such as cisplatin. However, these agents have been shown to induce tumor cell survival by inducing NF-κB activity. Phase I trials of bortezomib in solid tumors, including ovarian cancer, are summarized and examined to determine if the compound can overcome the impact of chemoresistance. In one trial of single-agent bortezomib in advanced malignancies, it was deemed a safe and manageable drug with potential efficacy in solid tumors. A second phase I trial explored inhibition of NF-κB with bortezomib to see if the drug rendered platinum agents more sensitive in ovarian cancer patients. Seven of the nine patients in the study had major responses to the combination of carboplatin and bortezomib. The two trials indicate promising results for bortezomib in patients with solid tumors and patients with recurrent ovarian cancer, but further investigation is warranted. © 2004 Elsevier Inc. All rights reserved. |
| Keywords: | cancer chemotherapy; cancer surgery; clinical trial; fatigue; neutropenia; review; cisplatin; doxorubicin; advanced cancer; diarrhea; drug efficacy; drug safety; solid tumor; antineoplastic agents; drug approval; drug targeting; cancer patient; recurrent cancer; cancer diagnosis; anorexia; ovarian neoplasms; cell survival; carboplatin; bortezomib; proteasome inhibitor; drug eruption; multiple myeloma; ovary cancer; sensory neuropathy; boronic acids; protease inhibitors; pyrazines; transcription initiation; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; dexamethasone; melphalan; immunoglobulin enhancer binding protein; antineoplastic activity; cancer cell culture; drug screening; drug resistance, neoplasm; fever; pruritus; chemotherapy induced emesis; drug mechanism; protein-serine-threonine kinases; drug response; tumor cell; malignant neoplastic disease; inhibition kinetics; down regulation; platinum derivative; loperamide; headache; taxane derivative; drug sensitivity; gynecologic cancer; beta adrenergic receptor blocking agent; calcium channel blocking agent; clinical trials; alpha adrenergic receptor blocking agent; humans; human; female; priority journal |
| Journal Title: | Seminars in Oncology |
| Volume: | 31 |
| Issue: | Suppl.16 |
| ISSN: | 0093-7754 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2004-12-01 |
| Start Page: | 22 |
| End Page: | 26 |
| Language: | English |
| DOI: | 10.1053/j.seminoncol.2004.10.015 |
| PROVIDER: | scopus |
| PUBMED: | 15799241 |
| DOI/URL: | |
| Notes: | Semin. Oncol. -- Cited By (since 1996):17 -- Export Date: 16 June 2014 -- CODEN: SOLGA -- Source: Scopus |
