Telomerase is perceived as an immortality enzyme that enables passing the Hayflick limit. Its main function is telomere restoration but only in a limited group of cells, including cancer cells. Since it is found in a vast majority of cancer cells, it became a natural target for cancer therapy. However, it has much more functions than just altering the metabolism of telomeres—it also reveals numerous so-called non-canonical functions. Thus, a question arises whether it is always beneficial to turn it off when planning a cancer strategy and considering potential side effects? The purpose of this review is to discuss some of the recent discoveries about telomere-independent functions of telomerase in the context of cancer therapy and potential side effects.

Currently, breast cancer appears to be the most widespread cancer in the world and the most common cause of cancer deaths. This specific type of cancer affects women in both developed and developing countries. Prevention and early diagnosis are very important factors for good prognosis. A characteristic feature of cancer cells is the ability of unlimited cell division, which makes them immortal. Telomeres, which are shortened with each cell division in normal cells, are rebuilt in cancer cells by the enzyme telomerase, which is expressed in more than 85% of cancers (up to 100% of adenocarcinomas, including breast cancer). Telomerase may have different functions that are related to telomeres or unrelated. It has been shown that high activity of the enzyme in cancer cells is associated with poor cell sensitivity to therapies. Therefore, telomerase has become a potential target for cancer therapies. The low efficacy of therapies has resulted in the search for new combined and more effective therapeutic methods, including the involvement of telomerase inhibitors and telomerase-targeted immunotherapy.

Human telomeres were one of the first discovered and characterized sequences forming quadruplex structures. Association of these structures with oncogenic and tumor suppressor proteins suggests their important role in cancer development and therapy efficacy. Since cationic porphyrin TMPyP4 is known as G-quadruplex stabilizer and telomerase inhibitor, the aim of the study was to analyze the anticancer properties of this compound in two different human breast-cancer MCF7 and MDA-MB-231 cell lines. The cytotoxicity of TMPyP4 alone or in combination with doxorubicin was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) and clonogenic assays, and the cell-cycle alterations were analyzed by flow cytometry. Telomerase expression and activity were evaluated using qPCR and telomeric repeat amplification protocol (TRAP) assays, respectively. The contribution of G-quadruplex inhibitor to protein pathways engaged in cell survival, DNA repair, adhesion, and migration was performed using immunodetection. Scratch assay and functional assessment of migration and cell adhesion were also performed. Consequently, it was revealed that in the short term, TMPyP4 neither revealed cytotoxic effect nor sensitized MCF7 and MDA-MB-231 to doxorubicin, but altered breast-cancer cell adhesion and migration. It suggests that TMPyP4 might substantially contribute to a significant decrease in cancer cell dissemination and, consequently, cancer cell survival reduction. Importantly, this effect might not be associated with telomeres or telomerase.

Breast cancer is one of the most frequently detected malignancies worldwide. It is responsible for more than 15% of all death cases caused by cancer in women. Breast cancer is a heterogeneous disease representing various histological types, molecular characteristics, and clinical profiles. However, all breast cancers are organized in a hierarchy of heterogeneous cell populations, with a small proportion of cancer stem cells (breast cancer stem cells (BCSCs)) playing a putative role in cancer progression, and they are responsible for therapeutic failure. In different molecular subtypes of breast cancer, they present different characteristics, with specific marker profiles, prognoses, and treatments. Recent efforts have focused on tackling the Wnt, Notch, Hedgehog, PI3K/Akt/mTOR, and HER2 signaling pathways. Developing diagnostics and therapeutic strategies enables more efficient elimination of the tumor mass together with the stem cell population. Thus, the knowledge about appropriate therapeutic methods targeting both “normal” breast cancer cells and breast cancer stem cell subpopulations is crucial for success in cancer elimination.

One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in selected miRNA levels in various breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3) treated with doxorubicin or cisplatin. The selection was based on literature data regarding the most commonly altered miRNAs in breast cancer (21-3p, 21-5p, 106a-5p, 126-3p, 126-5p, 155-3p, 155-5p, 199b-3p, 199b-5p, 335-3p, 335-5p). qPCR assessment revealed significant differences in the basal levels of some miRNAs in respective cell lines, with the most striking difference in miR-106a-5p, miR-335-5p and miR-335-3p—all of them were lowest in MCF7, while miR-153p was not detected in SK-BR-3. Additionally, different alterations of selected miRNAs were observed depending on the cell line and the drug. However, regardless of these variables, 21-3p/-5p, 106a, 126-3p, 155-3p and 199b-3p miRNAs were shown to respond either to doxorubicin or to cisplatin treatment. These miRNAs seem to be good candidates for markers of breast cancer cell response to doxorubicin or cisplatin. Especially since some earlier reports suggested their role in affecting pathways and expression of genes associated with the DNA-damage response. However, it must be emphasized that the preliminary study shows effects that may be highly related to the applied drug itself and its concentration. Thus, further examination, including human samples, is required.