Abstract 3496: Improvement of response to chemotherapy in breast cancer cells by the use of the non-oncologic drug minocycline
Authors: Bernemann Christof , Kiesel Ludwig 
Published: August 2015

Introduction

The majority of breast cancer patients receive (neo-) adjuvant chemotherapy. Although a high percentage of patients show good response - as shown by pathologic complete response - another high number of patients does not profit from chemotherapeutic treatments. Therefore, there is a high demand for improvement of chemotherapeutic treatments.

It has been proposed that non-oncologic drugs, which are used in treatment of other diseases, might represent a valid novel therapeutic approach, as these drugs have already been tested for side effects, etc. Nonetheless, a dramatic breakthrough by using non-oncologic drugs as single treatment agents has not been published so far.

However, we hypothesized that a combinatorial treatment using oncologic drugs as well as non-oncologic drugs might improve the response to classical cancer treating agents, e.g. chemotherapeutic agents.

Recently, we could show a sensitization of triple negative breast cancer cells to chemotherapy by using the anti-androgenic drug dutasteride in combination with either cisplatinum as well as paclitaxel (von Wahlde et al., 2014).

Currently, we deeply analyze the effect of another non-oncologic drug - minocycline - in the treatment of breast cancer cells. Minocycline has been described as a broad-spectrum tetracycline antibiotic. It has already been proposed that it might also improve chemotherapeutic treatments as well as radiation treatments (Sotomayor et al. 1992). However, an improvement of chemotherapy in breast cancer patients has not been described so far.

Methods

Breast cancer cells were treated with increasing concentrations of minocycline. Subsequently, cells were treated with minocycline in combination with different cytotoxic agents. Cell viability was measured using MTT assays. Molecular biological analyses were performed in order to dissect the mechanisms resulting in altered chemotherapeutic responses.

Results

When treated in the presence of minocycline alone, some breast cancer cells showed reduced viability only at high concentrations. The combinatorial treatment using minocycline plus cytotoxic agents however, greatly improved the response to the cytotoxic agents, as viabilitiy drastically decreased.

Conclusion

We conclude that the use of non-oncologic drugs might greatly improve the response to standard chemotherapeutic agents in the treatment of breast cancer. Thus, patients suffering from breast cancer might profit from a combinatorial application of both minocycline as well as standard chemotherapeutic agents.

As minocycline targets several distinct cellular components, a deeply analysis is needed in order to evaluate the mechanisms underlying the improved response to cytotoxic agents.

Citation Format: Christof Bernemann, Ludwig Kiesel. Improvement of response to chemotherapy in breast cancer cells by the use of the non-oncologic drug minocycline. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3496. doi:10.1158/1538-7445.AM2015-3496