Potential Therapeutic Targets in Triple Negative Breast Cancer

Triple negative breast cancers (TNBC) are often described as biologically aggressive tumors, with poorer survival compared to other breast cancer subtypes. The fact that TNBC lacks an obvious target like estrogen receptor and HER2 represents a major challenge in the management of these patients. Genomic analyses have revealed that TNBC comprises a diverse group of cancers, which have distinct molecular profiles and different prognosis. These studies also highlighted molecular aberrations that could serve as potential treatment targets. On the other hand, a high percentage of TNBCs express some important surface receptors that have been already exploited in the development of promising targeted therapies, which are currently tested in clinical trials. In this review, we will provide an overview on the molecular diversity of TNBC with special emphasis on the evolving role of some potential biomarkers that may be utilized in the near future.

Stimulation of apolipoprotein D secretion by steroids coincides with inhibition of cell proliferation in human LNCaP prostate cancer cells

Although steroid hormones are known to play a predominant role in the regulation of cell growth in hormone-sensitive cancers, their mechanisms of action, especially their interaction with growth factors and/or growth inhibitors, is poorly understood. We have recently observed that the effects of androgens and estrogens on the expression of the major protein found in human breast gross cystic disease fluid, protein-24, are opposite to their respective action on cell proliferation in human breast cancer cell lines. Somewhat surprisingly, the recent elucidation of the amino acid sequence of this progesterone binding protein reveals that this tumor marker is apolipoprotein D (apo D), a member of a superfamily of lipophilic ligand carrier proteins. The present study was designed to determine whether apo D is secreted by human prostate cancer cells and could thus be a new marker of steroid action in these cancer cells, and whether the sex steroid-induced stimulation of apo D secretion coincides with inhibition of cell proliferation. We took advantage of the biphasic pattern of the effect of steroids on the proliferation of the human prostate cancer LNCaP cell line, which offers the opportunity to discriminate between positive and negative steroid receptor-regulated cell growth processes. A 10-day exposure to low concentrations of dihydrotestosterone and testosterone caused a potent stimulation of LNCaP cell proliferation, whereas incubation with higher concentrations of these androgens led to a progressive decrease in cell proliferation towards basal levels. The biphasic action of androgens was also observed on apo D secretion, the effects on apo D secretion being inversely related to their action on LNCaP cell proliferation. Similar opposite biphasic effects were also observed with 9 other steroids, thus indicating that the stimulation of secretion of this new biochemical marker coincides with inhibition of cell proliferation in LNCaP human prostatic cancer cells.