Therapy Of Breast Cancer Cells Research Articles

Interleukin signaling in the regulation of natural killer cells biology in breast cancer.

In the field of breast cancer treatment, the immunotherapy involving natural killer (NK) cells is increasingly highlighting its distinct potential and significance. Members of the interleukin (IL) family play pivotal regulatory roles in the growth, differentiation, survival, and apoptosis of NK cells, and are central to their anti-tumor activity. These cytokines enhance the ability of NK cells to recognize and eliminate tumor cells by binding to specific receptors and activating downstream signaling pathways. Furthermore, interleukins do not function in isolation; the synergistic or antagonistic interactions between different interleukins can drive NK cells toward various functional pathways, ultimately leading to diverse outcomes for breast cancer patients. This paper reviews the intricate relationship between NK cells and interleukins, particularly within the breast cancer tumor microenvironment. Additionally, we summarize the latest clinical studies and advancements in NK cell therapy for breast cancer, along with the potential applications of interleukin signaling in these therapies. In conclusion, this article underscores the critical role of NK cells and interleukin signaling in breast cancer treatment, providing valuable insights and a significant reference for future research and clinical practice.

Trifluoromethyl-pyrrolidone phthalocyanine nanoparticles for targeted lipid droplet imaging and in vitro photodynamic therapy in breast cancer cells

Lipid droplets (LDs) serve as vital subcellular organelles, crucial for the maintenance of lipid and energy homeostasis within cells. Their visualization is of significant value for elucidating the intricate interactions between LDs and other cellular organelles. Despite the importance of LDs, the literature on the utilization of phthalocyanine-based photosensitizers for targeted LD imaging and two-photon imaging-guided photodynamic therapy (PDT) remains sparse. In this study, we have designed and synthesized trifluoromethyl-pyrrolidone silicon phthalocyanine (PyCF3SiPc). To enhance the water solubility of PyCF3SiPc and improve its tumor cells accumulation, we employed 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-mPEG2000) as a nanocarrier, thereby formulating DSPE@PyCF3SiPc nanoparticles. Our in vitro experiments in MCF-7 cells demonstrated that DSPE@PyCF3SiPc selectively targets and visualizes LDs, offering a reliable tool for tracking their dynamic movement. Moreover, DSPE@PyCF3SiPc demonstrates considerable phototoxicity against MCF-7 cells subjected to PDT underscoring its potential as an effective therapeutic agent. In conclusion, DSPE@PyCF3SiPc presents itself as a promising novel probe for the dual purpose of monitoring the dynamic movement of LDs and guiding imaging-assisted PDT. The development of this nanoparticle system not only advances our understanding of LD biology but also paves the way for innovative therapeutic strategies in oncology.

A tumor microenvironment-activated near-infrared photosensitizer enable efficient photodynamic therapy of breast tumor

As an emerging cancer therapy with high selectivity, minimally invasive and low side effects, photodynamic therapy (PDT) has become the focus of current researches. The breast cancer is a malignant tumor with the highest incidence in women. Thus, it is valuable for improving its treatment efficiency to construct efficient photosensitizer. To this end, we engineered a high stable near-infrared photosensitizer NPA-NH2 based on “step by step” strategy. By modifying the optically tunable amino group of NPA-NH2, a peroxynitrite (ONOO-) activated NPA-ONOO- theranostic agent with a new trifluoromethylsulfonamide recognization site was designed and synthesized. It possessed a good singlet oxygen-generating ability after ONOO- activation under 660 nm light, and a high sensitivity (limit of detection: 0.038 μM) and selectivity respond toward ONOO- in buffer solution. The theranostic agent was able to specially monitor ONOO- in tumor cells. Furthermore, we have succeeded in applying the NPA-ONOO- for efficient and precise photodynamic therapy of breast cancer cells and tumors in vivo. This work provides a new way for the design of highly stable photosensitizers and a reliable tool for effective treatment of breast tumors.

Antitumor effects of co-treatment of resveratrol with antitumor drugs in ER- and HER2-positive breast cancer cells are due to induction of apoptosis and modulation of estrogen receptor expression.

Resveratrol, a natural compound, may be an alternative to improving conventional breast cancer therapy. Thus, we assessed the capability of resveratrol at a low dose to enhance the in vitro effect of conventional theray in estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2)-positive breast cancer cells. Cell viability of breast cancer cells was measured with neutral red uptake assay. Apoptosis, autophagy, cell cycle progression and cell proliferation were detected through hypotonic fluorescent solution assay, formation of acidic vesicular organelles, flow cytometry, and bromodeoxyuridine assay, respectively. Western blotting was performed to study the expression of pro-apoptotic, anti-apoptotic and autophagic proteins, and estrogen receptors. Resveratrol combined with tamoxifen metabolites or trastuzumab reduced cell viability of ER- and HER2-positive breast cancer cells, respectively. This effect was mainly associated with induction of apoptosis due to a greater formation of hypodiploid nuclei, reduced protein expression of procaspase-7, Bcl-2, Bcl-xL, and PARP; and increased expression of cleaved PARP. Resveratrol decreased the expression of ERα and increased that of ERβ, contributing to the reduced viability on breast cancer cells. Combined treatments induced autophagy, evidenced by increased levels of acidic vesicular organelles and degradation of p62/SQSTM1 protein. Nevertheless, on inhibiting autophagy with 3-methyladenine, cell viability was further reduced and apoptosis was induced, suggesting a pro-survival role of autophagy, impairing apoptosis. Resveratrol increasead the in vitro cytotoxic effect of conventional therapy in breast cancer cells. However, it was necessary to block resveratrol-induced autophagy to improve the therapeutic response.

Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

IR-775 - Hyptis loaded bioactive nanoparticles for enhanced phyto-photothermal therapy of breast cancer cells

Photo-responsive therapy is an emerging treatment modality due to its bioimaging and therapeutic properties. Phototherapy induces localized hyperthermia and selectively eradicates cancer cells. The current study showed that multifunctional biodegradable liposome nanosystem (HIL NPs) containing Hyptis suaveolens bioactive molecules and IR-775, a NIR dye showed efficient bioavailability to cancer ells and allowed tumor ablation upon NIR laser irradiation. The resulting entities present in the nanosystem, i.e., bioactive molecules of Hyptis, serve as an anticancer agent, and IR-775 helps in the photothermal ablation of highly metastatic breast cancer cells. Hyptis suaveolens is a weed that grows rampantly, impeding the growth of neighboring plants; nonetheless, its bioactive compounds have demonstrated therapeutic benefits. The obtained HIL NPs, photothermally active liposome nanosystem showed a high fluorescence absorption peak in the NIR range and delivered a photothermal conversion efficiency of 55.20 % upon NIR laser irradiation. TEM and particle size analyzer revealed that HIL NPs have a size of 141 ± 30 nm with a spherical shape. The results of in-ovo (zebrafish) experiments have shown efficient bioimaging capabilities with minimal concentrations of HIL NPs compared to respective controls. Furthermore, in-vitro studies of HIL NPs against triple-negative breast cancer (4T1) indicated effective anticancer activity by a combined cytotoxic effect and hyperthermia. Tumor ablation was facilitated by reactive oxygen species production and hyperthermia, leading to DNA damage and apoptosis due to overexpression of ɣ-H2AX, Cathepsin B, and p53, which halted cancer cell proliferation. Therefore, HIL NPs demonstrated effective anticancer effects induced by combined phyto-photothermal therapy when evaluated against an in-vitro breast cancer model.

Resistance to hormone therapy in breast cancer cells promotes autophagy and EGFR signaling pathway.

Breast cancer is the leading cause of cancer deaths for women worldwide. Endocrine therapies represent the cornerstone for hormone-dependent breast cancer treatment. However, in many cases, endocrine resistance is induced with poor prognosis for patients. In the current study, we have developed MCF-7 cell lines resistant to fulvestrant (MCF-7Fulv) and tamoxifen (MCF-7Tam) aiming at investigating mechanisms underlying resistance. Both resistant cell lines exerted lower proliferation capacity in two-dimensional (2-D) cultures but retain estrogen receptor α (ERα) expression and proliferate independent of the presence of estrogens. The established cell lines tend to be more aggressive exhibiting advanced capacity to form colonies, increased expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and heterodimerization of ERBB family receptors and activation of EGFR downstream pathways like MEK/ERK1/2 and PI3K/AKT. Tyrosine kinase inhibitors tested against resistant MCF-7Fulv and MCF-7Tam cells showed moderate efficacy to inhibit cell proliferation, except for lapatinib, which concomitantly inhibits both EGFR and HER2 receptors and strongly reduced cell proliferation. Furthermore, increased autophagy was observed in resistant MCF-7Fulv and MCF-7Tam cells as shown by the presence of autophagosomes and increased Beclin-1 levels. The increased autophagy in resistant cells is not associated with increased apoptosis, suggesting a cytoprotective role for autophagy that may favor cells' survival and aggressiveness. Thus, by exploiting those underlying mechanisms, new targets could be established to overcome endocrine resistance.NEW & NOTEWORTHY The development of resistance to hormone therapy caused by both fulvestrant and tamoxifen promotes autophagy with concomitant apoptosis evasion, rendering cells capable of surviving and growing. The fact that resistance also triggers ERBB family signaling pathways, which are poorly inhibited by tyrosine kinase inhibitors might attribute to cells' aggressiveness. It is obvious that the development of endocrine therapy resistance involves a complex interplay between deregulated ERBB signaling and autophagy that may be considered in clinical practice.

Zn(II) porphyrin-encapsulated MIL-101 for photodynamic therapy of breast cancer cells.

The photodynamic treatment is a non-aggressive and clinically accepted procedure for removing selected cancer cells with the activation of a photosensitizer agent at a specific light. In this study, the zinc porphyrin (Zn[TPP]) was prepared and encapsulated into the MIL-101 (Zn[TPP]@MIL-101). It was used in photodynamic therapy (PDT) against MCF-7 breast cancer cells under a red light-emitting diode. The structure, morphology, surface area, and compositional changes were investigated using conventional characterization methods including FTIR, FESEM, EDX, and BET analyses. The MTT assay was performed under light and dark conditions to explore the ability of Zn[TPP]@MIL-101 in PDT. The results have demonstrated the IC50 of 14.3 and 81.6mg/mL for light and dark groups, respectively. As the IC50 revealed, the Zn[TPP]@MIL-101 could efficiently eradicate cancer cells using PDT.

The Impact of Gold Nanoparticles Synthesized by Essential Oil of Lemon and Plasma Jet Scheme on Growth Inhibition of Breast Cancer Cells

Gold nanoparticles (AuNPs) have gained significance due to their size and shape. The current study aimed to prepare AuNPs by using green - plasma jet and calculate the cellular toxicity of those manufactured nanomaterials. Aqueous gold tetrachloride salts (HAuCl<sub>4</sub>·4H<sub>2</sub>O) and essential oil of lemon peels in different ratios (0:10, 1:9, 2:8, and 3:7) were used to produce AuNPs. The synthesized green-prepared gold was characterized by ultraviolet-visible (UV-vis), X-ray diffraction (XRD), and field emission scanning electron microscopy (FESEM). UV-vis spectrum showed the highest absorption at 540 nm, and the patterns of XRD at the ratio (2:8) showed four peaks occurred at peaks at 2θ = 38.1, 44.3, 64.5, and 77.98. FESEM study illustrated that the AuNPs particle sizes range between (38-76 nm). The cell toxicity results have shown the effectiveness of the green synthesized AuNPs on the breast cancer (AMJ13) cell line. The breast cancer (AMJ13) cell line is found to be more inhibited when the concentration of AuNPs reaches 100%. According to the findings, creating nanoparticle materials for the therapy of breast cancer cells using green-cold plasma is a potential technique.

Effect of 13.56 MHz radiofrequency hyperthermia on mitotic cell cycle arrest in MCF7 breast cancer cell line and suggest a time interval for radiotherapy

After surgery, radiotherapy is the most common technique to treat breast cancer. Over the past decades, the thermal effects of radiofrequency-wave hyperthermia combined with radiotherapy have been used to increase radiosensitivity in cancer treatment. The cells have various radiation and thermal sensitivities at different stages of the mitotic cycle. Furthermore, ionizing radiation and the thermal effect of hyperthermia affect the cells' mitotic cycle and can partly induce cell cycle arrest. However, the time interval between hyperthermia and radiotherapy, as an essential factor influencing hyperthermia effect on cancer cells' cycle arrest, has not been studied before. In this study, we investigated the effect of hyperthermia on the MCF7 cancer cell cycle arrest in mitotic cycles at various selected time intervals after hyperthermia to find and propose appropriate time intervals between hyperthermia and radiotherapy. In this experimental study, we used the MCF7 breast cancer cell line to investigate the effect of 13.56 MHz hyperthermia (at a temperature of 43°C for a period of 20 min) on their cell cycle arrest. We performed the flowcytometry assay to assess the changes in the mitotic phases of the cell population at different time intervals (1, 6, 24, and 48 h) after hyperthermia. Our flowcytometry results indicated the 24-h time interval has the most significant effect on the cell population at S and G2/M phases. Therefore, the 24-h time interval can be proposed as the most appropriate time after hyperthermia for carrying out combinational radiotherapy procedure. Among various investigated time intervals examined in our research, the 24-h time interval can be proposed as the most appropriate time between hyperthermia and radiotherapy for combinational therapy of breast cancer cells.

Preparation of Gd-doped AuNBP@mSiO2 nanocomposites for the MR imaging, drug delivery and chemo-photothermal synergistic killing of breast cancer cells.

Under near-infrared (NIR) light, gold nanobipyramids (AuNBPs) exhibit a high photothermal conversion rate and photothermal stability, making them ideal mediators for photothermal therapy (PTT). In this study, highly purified AuNBPs are prepared, followed by coating their surfaces with mesoporous silica (mSiO2). The obtained AuNBP@mSiO2 nanocomplex exhibits an ellipsoidal shape with a relatively large specific surface, pore diameter and pore volume. To achieve MRI guided chemo-photothermal therapy of breast cancer cells, the nanocomplex is further coupled with the MRI contrast agent Gd-DTTA and the chemotherapeutic drug doxorubicin (DOX). The results indicated that under NIR light irradiation, AuNBPs exhibited promising PTT effects, while the cumulative release rate of DOX was significantly enhanced to 81.40%. Moreover, the chemo-photothermal therapy approach effectively eradicated 4T1 breast cancer cells. This work successfully confirms that chemo-photothermal synergistic therapy is an effective tumor treatment strategy and demonstrates the potential application of AuNBP@mSiO2 as a nano-drug delivery platform. Additionally, it introduces new ideas for the integrated study of breast cancer diagnosis and treatment.

The landscape of chimeric antigen receptor T cell therapy in breast cancer: Perspectives and outlook.

Chimeric antigen receptor-T (CAR-T) cell therapy is a revolutionary adoptive cell therapy, which could modify and redirect T cells to specific tumor cells. Since CAR-T cell therapy was first approved for B cell-derived malignancies in 2017, it has yielded unprecedented progress in hematological tumors and has dramatically reshaped the landscape of cancer therapy in recent years. Currently, cumulative evidence has demonstrated that CAR-T cell therapy could be a viable therapeutic strategy for solid cancers. However, owing to the immunosuppressive tumor microenvironment (TME) and heterogenous tumor antigens, the application of CAR-T cell therapy against solid cancers requires circumventing more challenging obstacles. Breast cancer is characterized by a high degree of invasiveness, malignancy, and poor prognosis. The review highlights the underlying targets of CAR-T cell therapy in breast cancer, summarizes the challenges associated with CAR-T cell therapy, and proposes the strategies to overcome these challenges, which provides a novel approach to breast cancer treatment.

Current State of Cell Therapies for Breast Cancer.

Metastatic breast cancer (BC) is an aggressive form of cancer and is an absolute challenge to treat. This review discusses the standard treatments available for metastatic BC. It further highlights the rationale for targeting oncodrivers, tumor-associated antigens, and neoantigens in BC. Explaining the significance of immune response in successful immunotherapeutic studies, it draws attention towards how adoptive cell therapy can be a useful immunotherapeutic tool. We focus on adoptive cell therapy in BC covering tumor-infiltrating lymphocyte therapy, engineered T cell receptor therapy, chimeric antigen receptor therapy, dendritic cell therapy and natural killer cell therapy. In this work, we aim to provide an overview of clinical data regarding the use of cellular immunotherapies in BC. Eventually, we conclude by proposing future adoptive cell therapy approaches, which can be used to cure BC.

Chitosan-based injectable in situ forming hydrogels containing dopamine-reduced graphene oxide and resveratrol for breast cancer chemo-photothermal therapy

Strategies combining nanomaterials’ chemotherapy and photothermal therapy hold an enormous potential for improving cancer treatment. Still, the translation of this modality has been hindered by the immunogenicity triggered by some of the polymers used for coating nanomaterials as well as by the nanostructures’ poor tumor uptake after systemic administration. To address this bottleneck, the formulation of injectable polymeric matrices capable of delivering/confining chemotherapeutics and nanomaterials into the tumor site has been gathering a great interest. In this work, ionotropically crosslinked chitosan-based injectable in situ forming hydrogels co-incorporating Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nano-agent) and Resveratrol (RES; chemotherapeutic drug), were prepared for the first time, to be applied in cancer chemo-photothermal therapy. The formulated hydrogels displayed injectability and in situ gelation as well as suitable physicochemical properties and good cytocompatibility. In vitro, the hydrogels’ photothermal therapy (DOPA-rGO@Gel +NIR light) only diminished the breast cancer cells’ viability to 72%. Moreover, cancer cells exposed to the hydrogels’ chemotherapy (RES+DOPA-rGO@Gel) still displayed a viability of 75%. In stark contrast, the hydrogels’ chemo-photothermal therapy (RES+DOPA-rGO@Gel +NIR light) was capable of decreasing cancer cells’ viability to just 31%. Overall, RES+DOPA-rGO@Gel presents an enormous potential for the chemo-photothermal therapy of breast cancer cells.

Staphylococcus aureus-Derived Extracellular Vesicles Enhance the Efficacy of Endocrine Therapy in Breast Cancer Cells.

The microbiome involved in the human estrogen metabolism is known as the estrobolome. This study aimed to show that the estrobolome can be used in breast cancer treatment. We first analyzed the blood microbiome composition of healthy controls and patients with breast cancer. In particular, we investigated the bacteria producing β−glucuronidase and/or β−galactosidase, which are involved in estrogen metabolism in the human body. Staphylococcus species were more abundant in healthy controls than in breast cancer patients and therefore were selected for further analyses. The effect of Staphylococcus aureus on endocrine therapy was analyzed by a combination treatment with tamoxifen. Analysis of the microbiome of blood samples showed that species producing β−glucuronidase were more abundant in breast cancer patients than in healthy controls. Further experiments confirmed that the efficacy of tamoxifen increased when administered in conjugation with the extracellular vesicles (EVs) of S. aureus. Based on our results, we deduced that S. aureus EVs could potentially be used as adjuvants for breast cancer treatment in the future.

MiR-206 conjugated gold nanoparticle based targeted therapy in breast cancer cells

MicroRNAs (miRNAs) are single-stranded, non-coding, 19–25 nucleotide RNA molecules that have been observed to be dysregulated in many diseases including cancer. miRNAs have been known to play an important role in cellular proliferation, differentiation, migration, apoptosis, survival, and morphogenesis. Breast cancer is heterogeneous in nature and contributed extensively to the increased mortality rate. miRNA can either be tumor-suppressive or oncogenic in nature. The level of expression of miRNA changes according to the subtypes of cancer and the mutation responsible for different cancers. miRNA mimicry or inhibition are emerging possible therapies to maintain the level of miRNA inside the cells. In order to have proper miRNA mimicry, the major hurdle is to deliver the miRNA mimics at the site of tumor. Metallic nanoparticles with modified surface can be used to solve the problem of miRNA delivery. MiR-206 is reported to be down-regulated in Luminal-A type of breast cancer. In the current manuscript, we aim to modify the surface of gold-nanoparticles (AuNPs) with PEG moiety and allow miRNA to attach to it. The fabricated nano-complex, not only delivered miR-206 but also caused cell death in MCF-7 by arresting cells in the G0-G1 phase and inducing apoptosis by downregulating NOTCH 3.

CAR-T Cell Therapy for Breast Cancer: From Basic Research to Clinical Application

Breast cancer rises as the most commonly diagnosed cancer in 2020. Among women, breast cancer ranks first in both cancer incidence rate and mortality. Treatment resistance developed from the current clinical therapies limits the efficacy of therapeutic outcomes, thus new treatment approaches are urgently needed. Chimeric antigen receptor (CAR) T cell therapy is a type of immunotherapy developed from adoptive T cell transfer, which typically uses patients' own immune cells to combat cancer. CAR-T cells are armed with specific antibodies to recognize antigens in self-tumor cells thus eliciting cytotoxic effects. In recent years, CAR-T cell therapy has achieved remarkable successes in treating hematologic malignancies; however, the therapeutic effects in solid tumors are not up to expectations including breast cancer. This review aims to discuss the development of CAR-T cell therapy in breast cancer from preclinical studies to ongoing clinical trials. Specifically, we summarize tumor-associated antigens in breast cancer, ongoing clinical trials, obstacles interfering with the therapeutic effects of CAR-T cell therapy, and discuss potential strategies to improve treatment efficacy. Overall, we hope our review provides a landscape view of recent progress for CAR-T cell therapy in breast cancer and ignites interest for further research directions.

MSBA-S - A pentacyclic sulfamate as a new option for radiotherapy of human breast cancer cells.

Many pentacyclic triterpenoids show anti-cancer and anti-inflammatory properties. Recently, we detected a pronounced cytotoxicity and radiosensitivity of two betulinyl sulfamates in human breast cancer cells. Besides betulinic acid scaffold (BSBA-S), we synthesized several new sulfamate-coupled scaffolds from oleanolic acid (OSBA-S), ursolic acid (USBA-S), platanic acid (PSBA-S) and maslinic acid (MSBA-S). Highest cytotoxicity was monitored in breast cancer cell lines after MSBA-S treatment showing in SRB assays IC50 values between 3.7μM and 5.8μM. Other sulfamate/triterpene conjugates, however, were less cytotoxic holding IC50 values between 6.6μM and >50µM, respectively. MSBA-S-treated breast cancer cells displayed significantly reduced clonogenic survival and an increased rate of apoptosis as compared to the other conjugates. In addition, MSBA-S in combination with irradiation resulted in effects on radiosensitivity in MDA-MB-231cells (DMF10=1.14). In particular, ROS formation was strongly assessed in MSBA-S-treated breast cancer cells. Our findings suggest that the sulfamate derivative of maslinic acid MSBA-S might be a new option for the radiation therapy in breast cancer cells.

Longitudinal FRET Imaging of Glucose and Lactate Dynamics and Response to Therapy in Breast Cancer Cells.

The reprogramming of cellular metabolism is a hallmark of cancer. The ability to noninvasively assay glucose and lactate concentrations in cancer cells would improve our understanding of the dynamic changes in metabolic activity accompanying tumor initiation, progression, and response to therapy. Unfortunately, common approaches for measuring these nutrient levels are invasive or interrupt cell growth. This study transfected FRET reporters quantifying glucose and lactate concentration into breast cancer cell lines to study nutrient dynamics and response to therapy. Two FRET reporters, one assaying glucose concentration and one assaying lactate concentration, were stably transfected into the MDA-MB-231 breast cancer cell line. Correlation between FRET measurements and ligand concentration were measured using a confocal microscope and a cell imaging plate reader. Longitudinal changes in glucose and lactate concentration were measured in response to treatment with CoCl2, cytochalasin B, and phloretin which, respectively, induce hypoxia, block glucose uptake, and block glucose and lactate transport. The FRET ratio from the glucose and lactate reporters increased with increasing concentration of the corresponding ligand (p < 0.005 and p < 0.05, respectively). The FRET ratio from both reporters was found to decrease over time for high initial concentrations of the ligand (p < 0.01). Significant differences in the FRET ratio corresponding to metabolic inhibition were found when cells were treated with glucose/lactate transporter inhibitors. FRET reporters can track intracellular glucose and lactate dynamics in cancer cells, providing insight into tumor metabolism and response to therapy over time.