Author Interviews, Breast Cancer, ESMO / 12.10.2016
Anti-Tumor Activity of PM01183 (lurbinectedin) in BRCA1/ 2-associated Metastatic Breast Cancer Patients
MedicalResearch.com Interview with:
Judith Balmaña MD
Medical Oncology
Hospital Vall d’Hebron and
Vall d’Hebron Institute of Oncology
Barcelona, Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Tumors with brca1 or brca2 mutations share homologous recombination repair deficiency, which confers sensitivity to different types of dna damaging agents. An understanding of the role of brca1 and brca2 in the repair of double-stranded dna damage opened a window of opportunity for treating brca mutation–associated cancers with targeted therapies.
Lurbinectedin is a trabectedin analog that specifically binds to cg-rich motifs with a selective mechanism of action: in living cells, lurbinectedin inhibits active transcription by degradation of elongating rna polymerase ii. This process occurs specifically on activated genes and is associated with the formation of double strand dna breaks and the collapse of replication forks. In addition, lurbinectedin exerts some antitumoral effect in the microenvironment by inhibiting the transcription of selected cytokines by tumor-associated macrophages, abrogating their protumoral properties. Observations that lurbinectedin was active against homologous-recombination-deficient cell lines led us to test it in patients with metastatic breast cancer having deleterious germline brca mutations.
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