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Case Report: Olaparib Shows Satisfactory Clinical Outcomes Against Small Cell Esophageal Carcinoma With ATM Mutation
Weiwei Wang1, Xiaoyan Zhang2, Yu Fang2
1Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China.
Abstract:
Small cell esophageal carcinoma (SCEC) is a rare, undifferential type of cancer, with a high degree of malignancy and early systemic metastasis. Radio-chemotherapy and surgery have been used as the primary treatment strategies for SCEC, but they both result in poor prognosis. There is need to develop an optimal standard treatment for the disease to improve prognosis and limit the related mortality. In this study, we described identification of driver mutations in ATM, a gene involved in homologous recombination deficiency (HRD) pathway, using next-generation sequencing on primary lesion and peripheral blood of a SCEC patient, who experienced recurrence after resection and radio-chemotherapy. In addition, we subjected the patient to olaparib, a PARP inhibitor, for the treatment of tumor with HRD and obtained a partial response. This is the first evidence implicating olaparib in successful treatment of SCEC with ATM mutation. The findings suggest that targeting mutations in HRD genes using olaparib or actionable genetic mutations using corresponding drugs, may be an effective therapeutic option for SCEC, although this requires further investigation.
Insights
This study identified an ATM mutation in small cell esophageal carcinoma (SCEC). Olaparib, a PARP inhibitor, showed a partial response in a patient with this mutation, suggesting a new treatment avenue for SCEC.
Area of Science:
- Oncology
- Genetics
Background:
- Small cell esophageal carcinoma (SCEC) is a rare, aggressive cancer with poor prognosis.
- Current treatments like radio-chemotherapy and surgery offer limited success.
Observation:
- Next-generation sequencing identified an ATM gene mutation in a recurrent SCEC patient.
- The patient's tumor exhibited homologous recombination deficiency (HRD).
Findings:
- Targeting the HRD pathway with olaparib (a PARP inhibitor) resulted in a partial response.
- This is the first report of olaparib efficacy in SCEC with an ATM mutation.
Implications:
- Targeting HRD pathway mutations with PARP inhibitors like olaparib may be a viable therapeutic strategy for SCEC.
- Further investigation is needed to establish olaparib as a standard treatment for SCEC patients with actionable genetic mutations.
