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

Meiyun Fan, Timothy C. Chambers

Research output: Contribution to journalReview article

155 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)253-267
Number of pages15
JournalDrug Resistance Updates
Volume4
Issue number4
DOIs
StatePublished - Jan 1 2001

Fingerprint

Mitogen-Activated Protein Kinases
Drug Therapy
Antineoplastic Agents
Neoplasms
Apoptosis
Pharmaceutical Preparations
Mitogen-Activated Protein Kinase Kinases
Cell Survival
Cell Death
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Cancer Research
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy. / Fan, Meiyun; Chambers, Timothy C.

In: Drug Resistance Updates, Vol. 4, No. 4, 01.01.2001, p. 253-267.

Research output: Contribution to journalReview article

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