Paclitaxel and concurrent radiation for lung, pancreatic, and gastric carcinomas: Significance of p53 gene mutations for treatment response

H. Choy, T. C. King, W. Akerley, H. Safran

Research output: Contribution to journalArticle

Abstract

Paclitaxel (Texol; Bristol-Myers Squibb Company, Princeton, NJ) and concurrent radiation (paclitaxel/RT) are being actively evaluated as treatment for locally advanced lung, pancreatic, and gastric cancers. Paclitaxel is a potent chemotherapeutic agent that interferes with mitotic spindle function to synchronize cells at G2M, the most radiosensitive phase of the cell cycle. Because G2M arrest is necessary but not sufficient for paclitaxel radiosensitization, other cellular factors must interact with paclitaxel to produce radiosensitization. We have investigated whether molecular genetic alterations that disturb cell cycle regulation in tumor cells affect the action of paclitaxel as a radiosensitizer. The p53 tumor suppressor gene serves a critical role at the G1S transition of the cell cycle by blocking entry into S phase under conditions that would result in genetic instability. Mutations in the tumor suppressor gene, p53, confer resistance to radiation therapy and most chemotherapeutic agents, including cisplatin and 5-fluorouracil. In striking contrast, we have now shown that p53 mutations in non-small cell lung cancer do not confer resistance to paclitaxel/RT. The effect of p53 mutations on response to paclitaxel/RT in pancreatic and gastric cancers is currently being investigated. Knowledge of specific genetic alterations in individual tumors may permit the selection of optimal therapeutic strategy for individual patients.

Original languageEnglish (US)
Pages (from-to)77-81
Number of pages5
JournalSeminars in Radiation Oncology
Volume7
Issue number3 SUPPL. 2
StatePublished - 1997

Fingerprint

p53 Genes
mutations
Paclitaxel
genes
lungs
Stomach
cancer
Radiation
Lung
Mutation
tumor suppressor genes
radiation
cycles
drugs
tumors
Cell Cycle
Therapeutics
Tumor Suppressor Genes
Pancreatic Neoplasms
spindles

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Radiation

Cite this

Paclitaxel and concurrent radiation for lung, pancreatic, and gastric carcinomas : Significance of p53 gene mutations for treatment response. / Choy, H.; King, T. C.; Akerley, W.; Safran, H.

In: Seminars in Radiation Oncology, Vol. 7, No. 3 SUPPL. 2, 1997, p. 77-81.

Research output: Contribution to journalArticle

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