Differences in effects of oncogenes on sensitivity to anticancer drugs
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Updated: Aug 17, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Tomoyuki Hamamoto1, Keiji Suzuki, Hitoshi Sasaki
1Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Abstract:
Methods to predict the responsiveness of a particular tumor to a particular anticancer drug are desirable not only for chemotherapy but also for chemoradiotherapy. Here, we examined the effects of viral or activated oncogenes on sensitivity to anticancer drugs by using SHOK (Syrian hamster Osaka-Kanazawa) cells and their transfectants. The IC50 of each transfectant was compared with that of the pSV2Neo transfected control. Cells transfected with the c-myc, v-mos, or v-fgr gene increased their sensitivity to bleomycin, while those transfected with the H-ras gene developed resistance. Resistance to cisplatin was conferred by the introduction of the H-ras or c-cot gene. In the case of adriamycin, the c-myc or c-cot transfectant increased sensitivity and the H-ras transfectant decreased it. Mitomycin C resistance was observed by the introduction of the K-ras gene. Thus, the H-ras gene was found to be involved in the development of resistance to three of the four anticancer drugs. In addition, we have for the first time shown that mos and cot have an effect on sensitivity to three and all of the four anticancer drugs, respectively. These results suggest that the expression of each oncogene would differently affect sensitivity to the four anticancer drugs used in this study, and this property could be a possible marker to predict chemosensitivity.
Insights
Oncogene expression influences anticancer drug sensitivity. Certain oncogenes like H-ras can cause drug resistance, while others may increase sensitivity, offering potential markers for predicting chemotherapy response.
Area of Science:
- Molecular oncology
- Cancer drug development
- Genetics and cancer biology
Background:
- Predicting tumor response to anticancer drugs is crucial for effective chemotherapy and chemoradiotherapy.
- Understanding how oncogenes affect drug sensitivity can lead to personalized treatment strategies.
Purpose of the Study:
- To investigate the impact of viral or activated oncogenes on cellular sensitivity to various anticancer drugs.
- To identify potential oncogene-based markers for predicting chemosensitivity in tumors.
Main Methods:
- Utilized Syrian hamster Osaka-Kanazawa (SHOK) cells and their transfectants expressing specific oncogenes (c-myc, v-mos, v-fgr, H-ras, c-cot, K-ras).
- Assessed drug sensitivity by comparing the IC50 values of oncogene-transfected cells against a pSV2Neo control.
- Tested sensitivity to four anticancer drugs: bleomycin, cisplatin, adriamycin, and mitomycin C.
Main Results:
- H-ras oncogene conferred resistance to bleomycin, cisplatin, and adriamycin, and K-ras to mitomycin C.
- c-myc and v-fgr increased sensitivity to bleomycin; c-myc and c-cot increased sensitivity to adriamycin.
- v-mos affected sensitivity to bleomycin and adriamycin, while c-cot impacted all four drugs tested.
Conclusions:
- Different oncogenes differentially modulate sensitivity to anticancer drugs.
- The expression patterns of specific oncogenes may serve as predictive markers for individual tumor chemosensitivity.
- Findings highlight the potential for oncogene profiling in tailoring cancer therapy.
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