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Clinical Outcomes of Genotype-Matched Therapy for Recurrent Gynecological Cancers: A Single Institutional Experience
Kiyoka Sawada1, Kentaro Nakayama1, Kohei Nakamura1
1Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan.
Abstract:
Recent advances in next-generation sequencing and genome medicine have contributed to treatment decisions in patients with cancer. Most advanced gynecological cancers develop resistance to chemotherapy and have a poor prognosis. Therefore, we conducted genomic tests in gynecological tumors to examine the efficacy and clinical feasibility of genotype-matched therapy. Target sequencing was performed in 20 cases of gynecological cancers (cervical cancer, 6; endometrial cancer, 6; and ovarian cancer, 6). Both actionable and druggable genes were identified in 95% (19/20) of the cases. Among them, seven patients (35%) received genotype-matched therapy, which was effective in three patients. Of the three patients, one patient with a PTEN mutation received everolimus, another patient with a TSC2 mutation received everolimus and letrozole, and the patient with a BRIP1 mutation received olaparib. Subsequently, disease control in these three patients lasted for more than half a year. However, all patients relapsed between 9 and 13 months after the initiation of genotype-matched therapy. In this study, the response rate of genotype-matched therapy was 43% (3/7), which may have contributed to improved prognoses. Therefore, genotype-matched therapies may help patients with refractory gynecological cancers achieve better outcomes.
Insights
Genomic testing identified actionable targets in 95% of advanced gynecological cancers. Genotype-matched therapies showed a 43% response rate, offering potential for improved outcomes in refractory cases.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Advanced gynecological cancers often develop chemotherapy resistance, leading to poor prognoses.
- Genomic profiling is crucial for identifying targeted treatment strategies.
Purpose of the Study:
- To evaluate the efficacy and clinical feasibility of genotype-matched therapy in patients with advanced gynecological cancers.
- To identify actionable genetic alterations in gynecological tumors.
Main Methods:
- Target sequencing was performed on 20 gynecological tumor samples (cervical, endometrial, ovarian).
- Patients with identified actionable mutations received genotype-matched therapy.
Main Results:
- Actionable and druggable genes were found in 95% of cases.
- Seven patients received genotype-matched therapy, with three (43% response rate) showing initial disease control.
- Specific mutations (PTEN, TSC2, BRIP1) responded to targeted agents like everolimus, letrozole, and olaparib.
Conclusions:
- Genotype-matched therapy demonstrates potential clinical utility in refractory gynecological cancers.
- While initial responses were observed, further research is needed to overcome treatment resistance and improve long-term outcomes.
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