Gene targets of antisense therapies in breast cancer

Expert Opin Ther Targets. 2002 Jun;6(3):375-85. doi: 10.1517/14728222.6.3.375.


Advances in molecular and cell biology have led to further understanding of the mechanisms of malignant growth and metastasis in human breast cancer cells. Initiation and progression of breast cancer results from mutations and the abnormal expression of many genes that control cellular proliferation, differentiation, invasion, metastasis and sensitivity to therapy (chemotherapy and radiation therapy). Inhibition of host immunity also plays a role in breast cancer progression. Many genes have been selected as targets for antisense therapy, including HER-2/neu, PKA, TGF-alpha, EGFR, TGF-beta, IGFIR, P12, MDM2, BRCA, Bcl-2, ER, VEGF, MDR, ferritin, transferrin receptor, IRE, C-fos, HSP27, C-myc, C-raf and metallothionein genes. The strategy behind antisense therapy is the development of specific therapeutic agents that aim to correct the mutations and abnormal expression of cellular genes in breast tumour cells by decreasing gene expression, inducing degradation of target mRNA and causing premature termination of transcription. Many in vitro and in vivo studies have investigated the therapeutic efficacy of oligonucleotides and antisense RNAs. These studies have demonstrated specific inhibition of tumour cell growth by antisense therapy and have shown synergistic inhibitory effects between antisense oligonucleotides or antisense RNA and conventional chemotherapeutic drugs used in the treatment of breast cancer. Antisense oligonucleotides have been modified to improve their ability to penetrate cells, bind to gene sequences and downregulate target gene function. Many delivery systems for antisense RNA and antisense oligonucleotides have been developed, including virus vectors (retrovirus, adenovirus and adeno-associate virus) and liposomes, to carry the antisense RNA or oligonucleotides through the cell membrane into the cytoplasm and nucleus of the tumour cells. However, in order to determine their feasibility antisense therapies need to be further investigated to determine their antitumour activity, pharmacokinetics and toxicity in breast cancer patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antisense Elements (Genetics) / pharmacology*
  • Antisense Elements (Genetics) / therapeutic use
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy*
  • Cell Cycle / drug effects
  • Cell Line, Tumor / drug effects
  • Clinical Trials as Topic
  • Drug Carriers
  • Drug Design*
  • Drug Resistance, Neoplasm / genetics
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Targeting
  • Genetic Therapy*
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use
  • Humans
  • Iron / metabolism
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / genetics
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry
  • Oligonucleotides / therapeutic use
  • RNA Precursors / antagonists & inhibitors
  • RNA, Neoplasm / antagonists & inhibitors
  • RNA, Small Nuclear / antagonists & inhibitors
  • Transfection


  • Antineoplastic Agents
  • Antisense Elements (Genetics)
  • Drug Carriers
  • Neoplasm Proteins
  • Oligonucleotides
  • RNA Precursors
  • RNA, Neoplasm
  • RNA, Small Nuclear
  • Iron