TY - JOUR
T1 - Paclitaxel and concurrent radiation for lung, pancreatic, and gastric carcinomas
T2 - Significance of p53 gene mutations for treatment response
AU - Choy, H.
AU - King, T. C.
AU - Akerley, W.
AU - Safran, H.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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U2 - 10.1016/S1053-4296(97)80062-8
DO - 10.1016/S1053-4296(97)80062-8
M3 - Article
AN - SCOPUS:0030792405
SN - 1053-4296
VL - 7
SP - 77
EP - 81
JO - Seminars in Radiation Oncology
JF - Seminars in Radiation Oncology
IS - 3 SUPPL. 2
ER -