Format

Send to

Choose Destination
See comment in PubMed Commons below
Drug Resist Updat. 2001 Aug;4(4):253-67.

Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy.

Author information

  • 1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Abstract

Antitumor agents, despite having diverse primary mechanisms of action, mediate their effects by inducing apoptosis in tumor cells. Cellular commitment to apoptosis, or the ability to evade apoptosis in response to damage, involves the integration of a complex network of survival and death pathways. Among the best-characterized pathways regulating cell survival and cell death are those mediated by the mitogen-activated protein kinase (MAPK) family. Not surprisingly, MAPK signaling pathways have been implicated in the response of tumor cells to chemotherapeutic drugs. Indeed, literature in this area has grown enormously in recent years, and the present review attempts to provide an overview and perspective of these advances. While the activities of the major MAPK subgroups are subject to modulation upon exposure of different types of cancer cell lines to diverse classes of antitumor agents, the response tend to be context-dependent, and can differ depending on the system and conditions. Despite these complexities, some important trends have surfaced, and molecular connections between MAPK signaling pathways and the apoptotic regulatory machinery are beginning to emerge. With increased evidence supporting a role for MAPK signaling in antitumor drug action, MAPK modulators may have potential as chemotherapeutic drugs themselves or as chemosensitizing agents. The ability of MAPK/ERK kinase (MEK) inhibitors to block survival signaling in specific contexts and promote drug cytotoxicity represents an example, and recent knowledge of the pro-apoptotic functions of JNK and p38 suggests possible new approaches to targeted therapy. However, it will be important first to extrapolate the knowledge gained from these laboratory findings, and begin to address the role of MAPKs in the clinical response to chemotherapeutic drugs.

PMID:
11991680
DOI:
10.1054/drup.2001.0214
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center