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[Cancer-associated gene abnormalities and chemosensitivity]
M Sakamoto1, K Umayahara, H Sakamoto
1Dept. of Gynecology, Sasaki Institute Kyoundo Hospital, Tokyo, Japan.
Abstract:
One of the most important clinical issues in cancer chemotherapy is the presence of intrinsic resistance or the appearance of acquired resistance against chemotherapy. As for intrinsic resistance, we had to perform direct chemo-sensitivity testing, or had to rely on the knowledge empirically acquired from randomized clinical trials. However, molecular or genetic markers associated with chemo-sensitivity have been reported recently. For example, inactivation of p53 or GML gene has been reported to be associated with chemo-resistance. Overexpression of topo-isomerase I has been reported to be associated with chemo-sensitivity to Topo I inhibitor. Overexpression of Thymidine Phosphorylase has been found to be associated with chemo-sensitivity to prodrug of 5-FU. By checking the status of such chemo-sensitivity markers prior to chemotherapy, it would be possible to predict the chemotherapeutic effect and even the necessity of the chemotherapy in the near future. In this article, we review the chemo-sensitivity markers reported so far, and methodology contributing to the discovery of new chemo-sensitivity markers. As a clinical study, 11 cases of ovarian cancer with high sensitivity to cisplatin-based chemotherapy and 29 cases of ovarian cancer with chemoresistance were analyzed by Comparative Genomic Hybridization (CGH). Copy number decrease in Xp, and copy number increase in 19q were observed in 13, 12 out of 29 resistant cases (45, 41%) and zero, 1 out of 11 sensitive cases (0, 9%), suggesting that -Xp and +19q were likely to be a genetic event associated with intrinsic drug-resistance (p = 0.006, 0.05, respectively). This effort should contribute to the discovery of new chemo-sensitivity and resistance markers.
Insights
Predicting cancer chemotherapy effectiveness is crucial. New genetic markers, like Xp and 19q in ovarian cancer, can identify drug resistance, guiding personalized treatment strategies.
Area of Science:
- Oncology
- Cancer Genomics
- Pharmacogenomics
Context:
- Chemotherapy resistance is a major clinical challenge in cancer treatment.
- Identifying reliable markers for chemoresistance is essential for effective patient management.
- Existing methods for predicting chemoresistance include empirical data and direct testing.
Purpose:
- To review known chemo-sensitivity markers and discovery methodologies.
- To investigate potential genetic markers associated with cisplatin resistance in ovarian cancer.
- To identify novel genetic markers for predicting chemotherapy response.
Summary:
- This study reviews chemo-sensitivity markers and their discovery. Comparative Genomic Hybridization (CGH) analysis of ovarian cancer cases revealed copy number decrease in Xp and copy number increase in 19q were significantly associated with cisplatin resistance.
- These genetic alterations (-Xp and +19q) suggest a role in intrinsic drug resistance, offering potential biomarkers for predicting treatment outcomes.
- The findings contribute to the ongoing effort to discover new chemo-sensitivity and resistance markers.
Impact:
- Enables prediction of chemotherapy effectiveness and necessity before treatment initiation.
- Facilitates the development of personalized medicine approaches in cancer therapy.
- Advances the understanding of genetic underpinnings of chemoresistance, paving the way for novel therapeutic strategies.