Cancer Stem Cells and Somatic Stem Cells as Potential New Drug Targets, and Prognosis Markers, and Therapy Efficacy Predictors in Breast Cancer Treatment

Abstract

Breast cancer (BC) is one of the leading causes of cancer death in women. Thus, the search for drug targets, markers of disease prognosis, and more efficient treatment options is relevant. We have conducted a pilot study including patients with luminal B stage breast cancer IIA-IIIB (T1-3N0-3M0), triple-negative BC, and HER+ BC (age range: 28 to 66 years). The control group consisted of healthy women of similar age. Presence and frequency of various populations of cancer stem cells (CSC) and somatic stem cells (e.g., hematopoietic stem cells, endothelial progenitor cells, and epithelial precursors) were assessed in the blood from the cubital vein, breast tumor tissue, and tissue adjacent to the tumor. Moreover, the sensitivity of CSC and somatic stem cells to drugs used in chemotherapy was assessed in vitro. Our results suggest that patients with BC can be divided into two distinct groups based on the frequency of aldehyde dehydrogenase positive cells (ALDH+ cells) in the assessed tissues (ALDHhi and ALDHlow). For each group of patients, different cellular biomarkers for the prognosis of metastasis are proposed. In patients within the ALDHhi group, potential biomarkers of metastasis are HSCs, CSC (CD227+CD44+CD24-), and epithelial tumor cells (CD44+CD24‒CD49f+). In contrast, epithelial tumor cells (CD326+CD44+CD24‒) and breast mesenchymal stem cells (CD326‒CD49f+) are proposed as cellular metastasis biomarkers in ALDHlow patients. We have shown that these cells are resistant to cytostatics and can thus act as potential contributors to tumor progression and formation of metastases. Since these cell types are present in the patient circulation, we hypothesize that they are potential markers of the disease prognosis and predictors of the efficacy of the treatment. To increase the effectiveness of chemotherapy, we propose to evaluating the efficacy of cytostatics in vitro using biopsy material.