Trabectedin for the treatment of breast cancer

Expert Opin Investig Drugs. 2016;25(1):105-15. doi: 10.1517/13543784.2016.1124086. Epub 2015 Dec 22.

Abstract

Introduction: Trabectedin is an anti-tumor compound registered in Europe and in several other countries, for the second-line treatment of soft tissue sarcoma (STS) and for ovarian cancer in combination with liposomal doxorubicin. Trabectedin inhibits cancer cell proliferation mainly affecting the transcription regulation. Trabectedin also acts as a modulator of tumor microenvironment by reducing the number of tumor associated macrophages (TAM). Because of its unique mechanism of action, trabectedin has the potential to act as antineoplastic agent also in several solid malignancies, including breast cancer (BC).

Areas covered: This article reviews the preclinical and clinical data of trabectedin focusing on development in metastatic BC (mBC). Comments regarding the nature and the results of these trials are included.

Expert opinion: Trabectedin is thought to have a crucial activity with defective DNA-repair machinery and also in modulating the tumor micro-environment and the immune-system of cancer patients. From the current available data, we recognize a potential activity of trabectedin in mBC and support the renewed efforts to better elucidate the value of trabectedin in this indication.

Keywords: BRCA mutation; DNA repair; metastatic breast cancer; trabectedin.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • DNA Repair / drug effects
  • Dioxoles / pharmacology
  • Dioxoles / therapeutic use*
  • Female
  • Humans
  • Neoplasm Metastasis
  • Tetrahydroisoquinolines / pharmacology
  • Tetrahydroisoquinolines / therapeutic use*
  • Trabectedin
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Tetrahydroisoquinolines
  • Trabectedin