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[Recent advance in gastric cancer chemotherapy]
1Dept. of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Abstract:
Because of the low chemosensitivity of gastric cancer to conventionally available agents, several approaches were investigated to design "order made" treatments using chemosensitivity tests, including the histoculture drug response assay (HDRA) which was useful in evaluating the appropriate cancer chemotherapy for the patients with Stage III/IV gastric cancer. A recent investigation using a molecular biological method was introduced to predict the sensitivity of gastric cancer specimens to 5-fluorouracil (5-FU) by dihydropyrimidine dehydrogenase (DPD) activity and its mRNA. The low activity of DPD and DPD mRNA resulted in the low sensitivity to 5-FU, although thymidylate synthetase activity was not related to the sensitivity to 5-FU. This method is promising, since a small amount of material obtained through gastrofiberscopy will be adequate to assess DPD mRNA to predict the sensitivity to 5-FU. On the other hand, some randomized control trials with a huge cohort have indicated the usefulness of a "docetaxel + cisplatin + 5-FU" regimen for advanced and recurrent gastric cancer, and "5-FU + LV + radiation" as an adjuvant therapy for advanced gastric cancer. Furthermore, the efficacy of adjuvant chemotherapy after curative resection for gastric cancer was warranted by a meta-analysis of 19 published randomized trials. The "order made" and "standard" therapies will be complementary in the further development of chemotherapy against gastric cancer.
Insights
Gastric cancer patients may benefit from personalized chemotherapy. Dihydropyrimidine dehydrogenase (DPD) activity predicts sensitivity to 5-fluorouracil (5-FU), guiding tailored treatments for better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gastric cancer exhibits low chemosensitivity to conventional agents.
- Developing personalized treatment strategies is crucial for improving patient outcomes.
- Current research explores molecular markers to predict drug response.
Purpose of the Study:
- To evaluate the efficacy of personalized chemotherapy approaches for gastric cancer.
- To investigate the role of dihydropyrimidine dehydrogenase (DPD) activity in predicting 5-fluorouracil (5-FU) sensitivity.
- To compare the effectiveness of "order made" treatments with established standard regimens.
Main Methods:
- Histoculture drug response assay (HDRA) for chemosensitivity testing.
- Molecular biological methods to assess dihydropyrimidine dehydrogenase (DPD) activity and mRNA levels.
- Analysis of randomized controlled trials and meta-analyses on chemotherapy regimens for advanced gastric cancer.
Main Results:
- Low DPD activity and DPD mRNA levels correlate with reduced sensitivity to 5-FU.
- Thymidylate synthetase activity was not found to be related to 5-FU sensitivity.
- Standard regimens like docetaxel + cisplatin + 5-FU and 5-FU + LV + radiation show efficacy in advanced/recurrent gastric cancer.
Conclusions:
- DPD activity assessment is a promising method for predicting 5-FU sensitivity in gastric cancer.
- Personalized ("order made") and standard chemotherapy approaches can be complementary.
- Further development of chemotherapy for gastric cancer can integrate both tailored and evidence-based strategies.