Abstract
Breast cancer can be classified into molecular subtypes. Tumors overexpressing HER2 protein are more aggressive and metastatic; hence, patients have a poor prognosis. Anti-HER2 strategies, such as the monoclonal antibody Trastuzumab (Tz), have therefore been developed. Despite this progress, not all patients respond to the treatment. Retinoic acid (RA) has been proposed as an adjuvant treatment of breast carcinoma because of its ability to inhibit cell growth. We evaluated the effect of Tz in combination with RA on the viability, adhesion, migration, invasion and expression of migration-related proteins in SKBR3 and BT-474 human breast cancer cells. MTT, pharmacological interaction analysis, immunofluorescence, adhesion/migration/invasion and Western blot assays were performed. The coadministration of both drugs synergistically decreased cell survival. Tz+RA significantly decreased adhesion/migration/invasion in both cell types. Tz+RA strongly reduced FAK and HER2 expression and induced nuclear FAK translocation. In addition, a granular distribution of HER2 receptor was observed after the combined treatment. In conclusion, the coadministration of both drugs in patients with this type of cancer could contribute to the improvement of their prognosis and reduce the adverse effects of therapy because the applied Tz doses would be lower due to the adjuvant effect of RA.
Highlights
Breast cancer is one of the most common cancers in women worldwide [1]
One of the existing anti-human epidermal growth factor receptor 2 (HER2) strategies is the use of the monoclonal antibody Trastuzumab (Tz) or Herceptin®, which binds to the extracellular domain of HER2
Tz was approved by the Food and Drug Administration (FDA) for patients with advanced breast cancers that express HER2, and Tz is currently the therapy of choice and the most widespread treatment for this tumor subtype [7]
Summary
Breast cancer is one of the most common cancers in women worldwide [1]. It is a heterogeneous disease that is classified into molecular subtypes according to the presence or absence of estrogen receptors (ER), progesterone receptors or human epidermal growth factor receptor 2 (HER2, known as ErbB-2). Amplification of HER2 gene occurs in 25–30% of breast cancers and results in high levels of HER2 protein expression [3]. This is accompanied by an increase in HER2 signaling and promotion of malignant cell growth and survival [4]. 40-60% of patients do not respond to the treatment or develop resistance to it [7, 9]. This fact calls for new therapeutic approaches based on the combination of www.oncotarget.com different drugs and the combination of targeted therapies have great potential
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