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Cellular signal transmission
Volume 26, Issue 12,
, pages 2843-2856
Author links open overlay panel, , , , ,
Breast cancer is the most common cancer in women worldwide. Understanding the biology of this malignant disease is a prerequisite for choosing the appropriate treatment. Cell cycle changes occur in many types of cancer, including breast cancer. Some of the popular new targeted agents in breast cancer include:Cyclin-dependent kinaseInhibitors (CDKIs), which are drugs that block the function of cyclin-dependent kinases (CDKs) and drugs that target proto-oncogenessignaling pathwayssuch as Notch, Wnt and SHH (Sonic Hedgehog). CDKIs are divided into selective and non-selective CDK inhibitors. CDKIs have been tested as monotherapy and combination therapy. The CDKI palbocyclib is now a promising therapeutic agent for breast cancer. This drug recently entered phase III studyestrogen receptor(ER) positive breast cancer after showing encouraging resultssurvival without progressionin phase II studies.
The tumor microenvironment is now recognized as a key factor in response to cancer therapy. The tumor microenvironment is increasingly recognized as a target for combination therapy in breast cancer. Current findings on signaling pathways in breast cancer are summarized and discussed here. In addition, the therapeutic targeting of the microenvironment in breast cancer is also examined.
Cell division and cell death are the two dominant physiological processes that regulate the homeostasis of normal tissues. Alteration of these two physiological processes plays a key role in the pathogenesis of cancer , a disease composed of immortal cells that can be fatal for patients. Major efforts to elucidate the components of the cell cycle are leading to new approaches to cancer therapy.
Genes encoding cell cycle components such as cyclin, CDKs and their endogenous inhibitors that occur under physiological conditions are commonly deregulated in many human cancers . For example, CDKs are hyperactive in some cancers, depending on overexpression of cyclins or downregulation of endogenous CDKIs . Based on the data, researchers are focusing on whether the CDK inhibition strategy can make cancer treatment more successful. Some studies suggest that inhibition of CDKs could be an effective treatment in many types of cancer, including breast cancer . Hormone therapy is a systemic treatment that is usually used as an adjuvant to reduce the risk of cancer returning after surgery. It is also used to treat cancer that has come back or spread after treatment. A major breakthrough in clinical oncology has offered the opportunity to expand the options for treating breast cancer patients with hormone therapy, using drugs that block estrogen from binding to its receptors on cancer cells, thereby preventing the cells from growing and spreading  . Some signaling pathways such as Notch, Wnt, SHH (Sonic Hedgehog) and others have recently been described as a new therapeutic target in breast cancer , , , , .
The breast microenvironment consists of extracellular matrix (ECM) and numerous stromal cell types, including endothelial and immune cells, fibroblasts, and adipocytes [ 11 ]. Recent studies have reported that cancer-associated fibroblasts (CAFs), which constitute the majority of the tumor stroma and tumor microenvironment, promote initiation, angiogenesis, invasion, and metastasis [ 11 ]. In breast cancer, CAFs not only promote tumor progression but also induce treatment resistance. Consequently, targeting CAFs offers a new opportunity to control therapy-resistant tumors . Breast tumor cells express certain Notch molecules and release factors that promote tumor cell survival and proliferation , , . The tumor microenvironment is now recognized as an important factor in tumor progression and response to therapy . Consequently, there is increasing interest in the development of new therapies that target the microenvironment, particularly regarding invasiveness and metastatic progression. Signals from the microenvironment, particularly those from transforming growth factor β (TGF-β), induce targeted de novo epigenetic changes in cancer-related genes [ 15 ]. TGF-β signaling in cancer has been reported to play two opposing roles, namely tumor suppression and tumor promotion, and its dysregulation is at least partially caused by epigenetic changes [ 15 ]. This review summarizes and discusses the current understanding of breast cancer signaling pathways with particular emphasis on the therapeutic potential of microenvironmental targeting.
Signaling pathways and hormones involved in breast cancer cell cycle and survival
Several proteins, signaling pathways and hormones are involved in the cell cycle and survival of breast cancer such as: B. CDKs (Cyclin Dependent Kinase), Notch, Wnt, SHH, Estrogen Receptor, HER2 (Human Epidermal Growth Factor Receptor 2) and others. Figure 1 shows proteins, cell cycle pathways and breast cancer survival.
CDK inhibitors in breast cancer
Breast cancer is the most common cancer in women worldwide  and some cell cycle changes have been identified in this disease. Checkpoint dysregulation plays a key role in some breast cancers. Alterations in signaling pathways involving cyclin, CDK, endogenous CDKI, and Rb protein are observed in almost all cancers, including breast cancer. Overexpression of cyclin D1 and cyclin E and reduced expression of CDKI p27Kip1 are some of them in human breast cancer , . Cyclin D1 amplification is
Therapeutic targeting of the microenvironment
New insights into the tumor microenvironment, both targeted and global, are identifying new therapeutic targets. Currently, three types of therapies targeting the tumor microenvironment are used in clinical practice: aromatase inhibitors (targeting the aromatase enzyme expressed mainly by stromal components), angiogenesis-modulating agents (including anti-VEGF receptor antagonists), and inhibitors of (HER) family such as trastuzumab, which inhibits receptor signaling in the epithelium
The era of targeted therapy has brought rapid advances in the treatment of breast cancer. Targeted therapies increase cure rates in localized breast cancer and prolong survival in metastatic breast cancer. The list of targets for drug therapy has expanded dramatically with a deeper understanding of the molecular pathology of breast cancer.
There is increasing evidence that the interplay between Notch, Wnt, HHS and major signaling pathways and their role in regulating TICs may promote tumorigenesis
All authors contributed to the design, preparation, editing and final revision of the manuscript.
Disclosure of Conflict of Interest
The authors declare no competing financial interests.
The authors thank the staff of their respective institutions for comments on the manuscript.
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Overview of treatment strategies for ER-positive breast cancer
2023, Biochemical Pharmacology(Video) Targeting Cancer Pathways: Understanding Immune Checkpoints
Estrogen receptor is the driving transcription factor in approximately 75% of all breast cancers targeted by endocrine therapies, but drug resistance is a common clinical problem. ESR1 point mutations in the ligand-binding domain are commonly identified in metastatic tumors and ctDNA (circulating tumor DNA) derived from ER-positive breast cancer patients on endocrine therapies. Although endocrine therapy and CDK4/6 inhibitor therapy have shown preclinical and clinical benefits in breast cancer, the development of resistance remains a major challenge, and the detailed mechanisms and potential therapeutic targets in advanced breast cancer remain to be elucidated. Since the interaction between tumor and tumor microenvironment (TME) plays an important role in tumor growth and metastatic growth, this effect could serve as key regulators in resistance to endocrine therapy and the transition of breast cancer cells to metastasis. In this article, we reviewed recent advances in endocrine therapy and the contribution of the TME to ER-positive breast cancer.
Role of NDRG1 in breast cancer pathogenesis and therapy
2023, Biochimica et Biophysica Acta – Cancer Reviews
Breast cancer (BC) is the leading cause of cancer death in women. This disease is heterogeneous, with clinical subtypes being estrogen receptor-α (ER-α) positive, human epidermal growth factor receptor 2 (HER2) overexpressing, or ER-α, progesterone receptor, and HER2 triple negative (TNBC). . Tumors that are ER-α positive and overexpress HER2 can be treated with drugs that target these proteins, including tamoxifen and pertuzumab, respectively. Despite these therapies, resistance and metastasis are problematic, and TNBC is difficult to treat due to the lack of suitable targets. Many studies examining BC and other tumors indicate a role for N-myc regulated gene 1 (NDRG1) as a metastatic suppressor. The ability of NDRG1 to inhibit metastasis is due in part to the inhibition of the first stage of metastasis, namely the epithelial-to-mesenchymal transition. Surprisingly, there are also reports that NDRG1 plays a pro-tumorigenic role in the pathogenesis of BC. The oncogenic effects of NDRG1 in BC have been reported to be related to lipid metabolism or mTOR signaling. The molecular mechanisms of how NDRG1 regulates the activity of multiple signaling pathways remain unclear. Therapeutic strategies to upregulate NDRG1 have been developed and include drugs from the di-2-pyridylketone thiosemicarbazone class. These compounds target oncogenic drivers in BC cells, suppress the expression of several important hormone receptors including ER-α, progesterone receptor, androgen receptor and prolactin receptor, and can also overcome tamoxifen resistance. Given the diverse role of NDRG1 in BC pathogenesis, further studies are needed to investigate which subset of BC patients will benefit from NDRG1 up-regulating pharmacopoeias.
NRF2 signaling pathway: An integrated prognostic and gene expression profiling analysis in breast cancer
2023, Pathology Research and Practice
Breast cancer is the most commonly diagnosed malignancy in women and a major public health concern. The NRF2 axis is a cellular protective signaling pathway that protects both normal and cancer cells from oxidative damage. NRF2 is a transcription factor that binds to gene promoters containing antioxidant response element-like sequences. In this report, the differential expression of NRF2 pathway components as well as the association of NRF2 pathway mRNAs with various clinicopathological features including molecular subtypes, tumor grade, tumor stage and methylation status in breast cancer were examined using METABRIC and TCGA datasets. In the current report, our results demonstrated the dysregulation of several NRF2 signaling components in breast cancer patients. In addition, there were negative correlations between NRF2 gene methylation and mRNA expression. The expression of NRF2 genes differed significantly between different subtypes of breast cancer. In conclusion, significant dysregulation of NRF2 signaling components suggests an important role for these genes in breast cancer. Based on the clear correlations between mRNA expression and methylation status, DNA methylation could be one of the mechanisms regulating NRF2 signaling in breast cancer. The differential expression of Hippo genes in different molecular subtypes of breast cancer suggests that NRF2 signaling may function differently in different breast cancer subtypes. Our data also highlight an interesting correlation between transcription of NRF2 components and tumor grade/stage in breast cancer.
Network pharmacological investigation of the mechanism of action of tetradrine against breast cancer
2023, Phytomedizin Plus
These reports are in turn supported by KEGG pathway analysis, as discussed later in this article. Mechanistic pathways of malignancy in breast cancer have reported involvement of MAPK, PI3K/Akt/nuclear factor kappa B (NFκB), TGF-β, Hedgehog (Hh), Notch, Wnt/β-catenin and Hippo pathways (Nwabo Kamdje et. al ., 2014; Yousefnia et al., 2020). Similarly, in the present study, KEGG pathway enrichment analysis performed with DAVID tool also led to the annotation of 37 VPTTs showing their role in cancer signaling pathways such as Wnt, mTOR, PI3-Akt, Jak-STAT, Calcium, MAPK. HIF-1, VEGF, estrogen, p53, cell cycle and apoptosis pathways (Fig. 3, Supplementary Table S7).
tetrandrine, a dibenzylisoquinoline alkaloidStefania Tetrandrawas used in the present study. its rootsS. tetandrais one of the main components of Traditional Chinese Medicine (TCM) herbal preparations viz. Fang Ji, Han-Dan-Gan-Le, Han-Dan-Gan-Le, Fang-Ji-Huang-Qi-Tang and Fang-Ji-Fu-Ling-Tang act as diuretics, anti-inflammatory and anti-rheumatic. Alkaloids are its main constituentsS. tetandraThe roots and tetrandrine are one of the important dibenzylisoquinoline alkaloids in this herb.
In the present study, the network pharmacology approach was used to identify key cancer signaling pathways and protein molecules that tetradrine targets to induce antitumor activity in breast cancer.
Potential targets of tetradrine against breast cancer were selected from previously published articles and public databases and used in protein interaction (PPI) network analysis, gene ontology (GO) and pathway enrichment analysis.
PPI network analysis revealed 65 nodes, 315 edges, and a clustering coefficient of 0.493. Tetradrine mainly targeted the proteins of mTOR, PI3-Akt, cell cycle and MAPK signaling pathways, in addition to its effects on cellular, biological and molecular functions as observed by genomic ontology and KEGG analysis.
Tetrandrine exerts antitumor activity in breast cancer by targeting PI3K-Akt, mTOR and MAPK as well as cell cycle pathways.
Role of STAT3 in breast cancer development, progression, proliferation and metastasis and strategies for delivery of JAK and STAT3 inhibitors
2022, Life Sciences
Breast cancer (BC) accounts for the majority of cancers in the female population. Abnormal activation of various signaling pathways has become a problem. The JAK-STAT signaling pathway is activated in many types of cancer, including BC. STAT3 is widespread in BCs, as 40% of BCs have phosphorylated STAT3. JAK-STAT signaling is critical for proliferation, survival, metastasis, and other cellular events associated with the tumor microenvironment. Therefore, targeting this signaling pathway has become an area of interest for researchers.
This review article focuses on the role of STAT3 in the onset, proliferation, progression and metastasis of BC. The role of various phytochemicals, synthetic molecules and biologics against JAK-STAT and STAT3 in different cancers was discussed, with special emphasis on BC.
JAK and STAT3 are involved in different phases from initiation to metastasis. Targeting this pathway is a promising approach to inhibit the various stages of BC growth and prevent metastasis. A number of phytochemical, synthetic and biological molecules have shown potential inhibitory effects on JAK and STAT3, paving the way for the development of better BC therapeutics.
Novel doxorubicin/trans-ferulic acid-targeted PLGA nanoparticle combination doxorubicin/folate-targeted trans-ferulic acid: in vivo superiority over standard chemotherapy for the treatment of breast cancer
2022, Biomedicine and Pharmacotherapy
Because the oncogenic role of Notch in cancer is believed to be mediated through its interaction with various signaling pathways and not just Wnt signaling (61), we were motivated to investigate the ability of the combination of Dox/FA-PLGA-TFA NPs to control of Notch in assessing interactions with other signaling pathways such as estrogen, progesterone and HER2 signaling pathways. Rizzo et al. and Lamb et al. showed that stimulation of Notch and Wnt signaling directly correlates with ERα expression [62,63], which in turn can induce PR and HER2 expression [64,65]. In relation to this, the expression of ERα, PR and HER2 proteins was significantly increased in the BC group.
Doxorubicin/cyclophosphamide (AC) is one of the standard adjuvant anthracycline-containing regimens still used to treat breast cancer. Cancer cell resistance and AC-induced side effects make treatment suboptimal and worsen patients' quality of life. This study aimed to improve the efficacy of trans-ferulic acid (TFA) by loading it into folate receptor-targeted polylactic-co-glycolic acid nanoparticles (FA-PLGA-TFA-NPs). Furthermore, the antitumor efficacy of the doxorubicin (Dox)/FA-PLGA-TFA-NPs combination against dimethylbenz[ONE]Anthracene (DMBA)-induced breast cancer and its safety profile.
FA-PLGA-TFA NPs were optimally prepared and characterized. The levels of Notch1, Hes1, Wnt-3a, β-catenin, MMP-9, cyclin D1, permeability glycoprotein (P-gp), ERα, PR, and HER2 were evaluated as a measure of the antitumor efficacy of different treatment protocols. Cardiac and bone histopathology, ALT, AST, ALP, CK-MB and WBC measurements were evaluated to ascertain the safety profile of the combination.
Dox/FA-PLGA-TFA NPs not only inhibited Notch signaling but also suppressed Notch synergy with Wnt, estrogen, progesterone and HER2 signaling pathways. Interestingly, Dox/FA-PLGA-TFA-NPs reduced P-gp levels and preserved heart, bone and liver health and leukocyte count.
Dox/FA-PLGA-TFA-NPs reduced the side effects of each single drug while exerting excellent antitumor activity that overcomes the AC regimen by bypassing tumor cell resistance and exhibiting a superior safety profile.(Video) Tumor-immune Microenvironment During neoadjuvant targeted therapy in HER2-positive breast cancer
Transmembrane signaling in Saccharomyces cerevisiae as a model for signaling in metazoans: state of the art after 25 years
Cellular Signalling, Volume 26, Issue 12, 2014, pp. 2865-2878
In the very first article that appeared onCellular signal transmission, published in the first issue in October 1989, we examined signal transduction pathways inSaccharomyces cerevisiae. Although this yeast was already a powerful model organism for studying cellular processes, it was not yet a valuable tool for studying signaling cascades. Therefore, in 1989 we discussed only two signaling pathways, Ras/cAMP and the mating signaling cascade (Fus3). Basic insights into these signaling pathways have undoubtedly contributed to the realization that yeast is a relevant model for understanding signaling in higher eukaryotes. As a result, many signal transduction pathways have been discovered over the past 25 yearsS. cerevisiae, including the high osmotic glycerol kinase (Hog1), Stl2/Mpk1 and Smk1 mitogen-activated protein (MAP) pathways, the TOR, AMPK/Snf1, SPS, PLC1 and Pkr/Gcn2 cascades and systems that recognize and respond to different types of stress . Many cascades have been identified as rational signaling pathways in mammals since their discovery in yeast. Here we discuss advances in understanding signalingS. cerevisiaethe last 25 years. When all pathways are analyzed together, some important themes emerge. First, the wiring of cascading signals may not be the same everywhereS. cerevisiaestrains, but is likely specific to each genetic background. This situation complicates efforts to decipher and generalize these reaction networks. Second, Ras/cAMP and TOR cascades are central signaling pathways that affect all processes in yeast cell life, whereas yeast MAP kinase signaling pathways are not essential. Yeast cells lacking all MAP kinases proliferate normally. Another issue is the existence of central molecular connections, either as single proteins (e.g. Msn2/4, Flo11) or as multisubunit complexes (e.g. TORC1/2), which are regulated through multiple pathways and in turn they determine the fate of the cell. It is also apparent that lipid signaling is less intense in yeast than in higher eukaryotes. Finally, feedback regulatory mechanisms appear to be at least as important and powerful as the signaling pathways themselves. on its 50th anniversaryCellular signal transmissionin 2039.
Regulators and Mechanisms of Anoikis in Triple Negative Breast Cancer (TNBC): A Review
Critical Reviews in Oncology/Hematology, Band 140, 2019, S. 17-27
Metastases result in poor prognosis and reduced disease-free survival in breast cancer patients, particularly in patients with triple-negative breast cancer (TNBC) that is resistant to current therapies. Anoikis is a type of apoptosis caused by the detachment of cells from the native extracellular matrix, preventing the attachment of detached cells to other organs of the body. Anoic resistance is a critical cause of tumor growth and progression. Therefore, understanding the molecular signaling pathways associated with anoikis is important for designing effective therapies for TNBC. Several compounds have been shown to have the potential to modulate anoikis in breast cancer cells, such as DSF, AEB071, nanoencapsulated doxorubicin, berberine, salinomycin, PEM POL5551, AL10, 5-azacytidine, a synthetic flavonoid derivative (tubeBMSide GL-V9 -V ) and HPW-RX40. We reviewed the molecular basis of anoikis regulation, its potential role as an important target to inhibit metastasis in TNBC, and potential modulators of anoikis that could serve as drug candidates.
Estrogen signaling and the unfolded protein response in breast cancer
The Journal of Steroid Biochemistry and Molecular Biology, Band 163, 2016, S. 45-50
Activation of the unfolded protein response (UPR) confers resistance to antiestrogens and chemotherapy in estrogen receptor-α (ERα)-positive and triple-negative breast cancers. Among the regulators of the UPR in breast cancer is estrogen signaling. Estrogen modulates important components of UPR expression, and ER is associated with the susceptibility of cancer cells to UPR-regulated apoptosis. Recent studies have confirmed the interplay between ER and UPR and suggest new therapeutic strategies combining targeting of both signaling pathways. These agents may be more effective in suppressing tumorigenic adaptation mechanisms and benefit patients with refractory disease.
Molecular changes in breast cancer and mechanisms of resistance to endocrine therapy
Progress in Molecular Biology and Translational Science, Band 144, 2016, S. 539-562
Estrogen receptors (ERs) are expressed in 75% of breast cancers. ERs and their estrogens play a key role in the development and progression of breast cancer. ERs have genomic activity that involves directly modulating the expression of genes important for cell growth and survival through their classical nuclear receptors. Nongenomic activity is mediated by membrane receptor tyrosine kinases that activate signaling pathways, resulting in activation of ER signaling pathway regulators.
Endocrine therapies inhibit the growth activity of estrogen. ERs-positive breast cancers may exhibit de novo or acquired endocrine resistance. Mechanisms of resistance to endocrine therapy are complex and involve dysregulation of ER signaling, growth factor receptor signaling, cell cycle machinery, and the tumor microenvironment.
In this chapter, we will review the literature on the biology of ERs, proposed mechanisms of endocrine therapy resistance, and their clinical implications.
Co-targeting of estrogen receptor and HER2 signaling pathways in breast cancer
The Chest, Volume 23, Issue 1, 2014, pp. 2-9
The steroid hormone estrogen receptor (ER) and the human epithelial growth factor receptor 2 membrane growth factor tyrosine kinase receptor (HER2) are the mediators of two key pathways involved in breast cancer development, invasive behavior and cell growth. Coexpression of these receptors leads to specific biological features that are not yet fully understood. However, these include relative resistance to hormone therapy and chemotherapy, as well as better long-term outcomes from ER and worse outcomes from HER2 expression. The ER and HER2 signaling pathways interact with each other, as do many biological networks, and this creates opportunities for therapeutic co-targeting with drugs that modulate these respective pathways. However, relatively few studies have been conducted to test the simultaneous manipulation of ER and HER2. The avoidance of chemotherapy side effects is an attractive feature that has further fueled research into this strategy. However, the only dual-target strategy that has been approved by some regulatory agencies is the combination of aromatase inhibitor hormone therapy and the HER2 kinase inhibitor lapatinib. Other dual combinations have also shown benefit, although most trials compared hormonal therapy with or without HER2-targeted agents rather than vice versa, limiting the application of this concept to routine clinical practice, particularly when chemotherapy is also used. New generation signal transduction inhibitors can increase the effectiveness of hormone therapy. One such example of mTOR blockade with everolimus is currently in the clinic. The logical progression of co-targeting ER and HER2 is the discovery and clinical testing of "synthetic lethal" combinations that target different signaling pathways and result in quantum improvements compared to either treatment alone. Molecular annotation of human cancers may further support personalized combination therapies based on the unique circuitry of an individual patient's tumor, with the potential to deliver much more than incremental survival gains.
Protein tyrosine phosphatases as novel targets in breast cancer therapy
Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, Band 1836, Ausgabe 2, 2013, S. 211–226
Breast cancer is associated with overactivation of protein tyrosine kinases (PTKs), and recent studies have shown that selective tyrosine dephosphorylation by protein tyrosine phosphatases (PTPs) of specific substrates, including PTKs, activates or inactivates oncogenic signaling pathways in the development of breast cells. human breast cancer. . related procedures. Here we review current knowledge on the involvement of PTPs in breast cancer as key regulators of PTKs targeted by breast cancer therapy, such as HER1/EGFR, HER2/Neu and Src. The functional interplay between PTKs and PTPs that activate or inactivate PTKs and its implications for novel breast cancer therapies based on targeting specific PTPs are discussed.
Copyright © 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
Overview of cell signalling mediated by the tyrosine kinase receptors (RTKs) Her2/Neu and estrogen receptors (ERs), two key components of breast cancer development. Their activation initiates the PI3K/Akt/mTOR and MAPK pathways, finally promoting cell growth, proliferation, survival, and other hallmarks of cancer.What is the therapeutic target for breast cancer? ›
Breast cancer targeted therapy uses drugs that block the growth of breast cancer cells in specific ways. For example, targeted therapy may block the action of an abnormal protein (such as HER2) that stimulates the growth of breast cancer cells.What is the role of tumor microenvironment in breast cancer and targeted therapies? ›
The tumor microenvironment plays a crucial part in the development, growth, and progression of the tumor and the resistance that is developed against the therapy being applied. It has drawn a lot of attention for treating breast cancer.What is the role of microenvironment in breast cancer? ›
Interaction between the cells in the tumor microenvironment leads to enhanced production of cytokines, growth factors, angiogenic factors and proteolytic enzymes that help in sustaining tumor growth, promoting angiogenesis, and tumor cell invasion and metastasis.What are the 4 types of cell signaling pathways? ›
There are four basic categories of chemical signaling found in multicellular organisms: paracrine signaling, autocrine signaling, endocrine signaling, and signaling by direct contact.What are the three Signalling pathways? ›
The molecular components of these signal transduction pathways are always activated by a chemical signaling molecule. Signaling molecules can be grouped into three classes: cell-impermeant, cell-permeant, and cell-associated signaling molecules (Figure 8.3).What are therapeutic targets for cancer treatment? ›
Targeted therapy is a type of cancer treatment. It uses drugs to target specific genes and proteins that help cancer cells survive and grow. Targeted therapy can affect the tissue environment that cancer cells grow in or it can target cells related to cancer growth, like blood vessel cells.What are two ways in which therapeutic target cancer? ›
There are two main types of targeted therapies: small molecule medicines and monoclonal antibodies. Small molecule medicines are small enough to slip inside cancer cells and destroy them.What are the therapeutic targets? ›
A therapeutic target is a biological molecule, biological pathway, or physiolocal response that is associated with a particular disease process and may be inhibited or activated by a therapy in a way that will change the course of the disease in a positive way.What is the role of tumor microenvironment in cancer therapy? ›
Tumor survival and function are regulated or promoted by the tumor microenvironment (TME). The interaction between TME structural components and cells permits cancer cells to acquire an invasive phenotype, spreading to distant sites from the primary site via a complex and multistep metastatic cascade.
The tumor microenvironment shapes the fate of DCs by providing environmental cues that either create an immune response to tumor cells or accept them. Cytokines secreted from the TME trigger DCs to tolerate the presence of tumor cells and block the induction of an immune response.What is the role of the microenvironment in tumor growth? ›
The tumor microenvironment consists of numerous pro-angiogenic factors, including VEGF, bFGF, and PDGF. These factors are secreted by tumor cells or tumor-infiltrating lymphocytes or macrophages, and can activate pro-angiogenic signaling pathways to promote tumor angiogenesis, growth, invasion, and metastasis.What are microenvironmental factors in cancer? ›
Tumor microenvironment (TME) is characterized by some special factors such as low extracellular pH, high level of reactive oxygen species, hypoxia, and over-expressed certain proteases in comparison with normal tissue.Why does the environment matter for breast cancer? ›
Proteins produced by developing mammary tissue may change after exposure to bisphenol A, a chemical found in many plastic products, and other pollutants in the environment. These exposures may alter cells in ways that contribute to breast cancer.What is the tumor microenvironment and why is it important to understand the tumor microenvironment? ›
The tumor microenvironment is the ecosystem that surrounds a tumor inside the body. It includes immune cells, the extracellular matrix, blood vessels and other cells, like fibroblasts. A tumor and its microenvironment constantly interact and influence each other, either positively or negatively.What is an example of a signalling pathway? ›
There is an almost staggering array of signaling pathways in a multicellular organism. The types of receptors and their second messengers do have similarities but can also be vastly different from each other. Some examples of signal transduction pathways include vision and touch and hormones.What are key signalling pathways? ›
The key regulatory pathways, such as MAPK pathway, PI3K/AKT/mTOR signaling, and Wnt/β-catenin signaling pathway, play essential roles in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism, and so on.What are signaling pathways? ›
Describes a series of chemical reactions in which a group of molecules in a cell work together to control a cell function, such as cell division or cell death. A cell receives signals from its environment when a molecule, such as a hormone or growth factor, binds to a specific protein receptor on or in the cell.What are the 5 primary types of cell signaling? ›
- Paracrine signalling.
- Autocrine signalling.
- Endocrine signalling.
- Direct Contact.
In this review, two major signal transduction pathways, cAMP-dependent pathway and mitogen-activated protein kinase (MAPK) pathway, will be discussed. Both pathways are highly relevant to modulation of differentiation and proliferation in T. cruzi by phosphorylating a set of specific substrate proteins.
Common adjuvant therapies include chemotherapy, radiation therapy and hormone therapy.How are targets for targeted cancer therapies identified? ›
Once healthcare providers understand the genetic mutation changing a healthy cell into a cancer cell, they identify specific cancer cell parts to target for treatment. Sometimes, these are targets on cancer cells surfaces. Other times, the targets are substances inside cancer cells.What 3 factors work together to produce successful therapeutic treatment? ›
The first is the use of evidence-based treatment that is deemed appropriate for your particular issue. The second important factor is the clinical expertise of the psychologist or therapist. The third factor is your own characteristics, values, preferences, and culture.What is the use of signal targets towards therapy of cancer? ›
Deliver cell-killing substances to cancer cells.
Some monoclonal antibodies are combined with cell-killing substances such as toxins, chemotherapy drugs, or radiation. Once these monoclonal antibodies attach to targets on the surface of cancer cells, the cells take up the cell-killing substances, causing them to die.
There are two ways by which targeting of nanoparticles can be achieved, namely passive and active targeting. Passive targeting allows for the efficient localization of nanoparticles within the tumor microenvironment. Active targeting facilitates the active uptake of nanoparticles by the tumor cells themselves.What are the 5 phases of treatment in therapeutic community? ›
- I – ENTRY PHASE. Occurs to assimilate the individual into the TC. ...
- II – JUNIOR PHASE. Continues the increasing levels of pro-social attitudes, behaviors, and responsibilities molded by the TC environment. ...
- III – SENIOR PHASE. Introduces the residents to social integration. ...
- IV – RE- ENTRY and AFTERCARE.
The authors discuss five key common factors: the therapeutic relationship, motivation, corrective experiencing, insight, and self‑efficacy, which serve as heuristics for therapists of any background.What are the 5 components of the therapeutic relationship? ›
The key elements of a therapeutic relationship include unconditional acceptance, empathy, genuineness, attending and listening, open-ended questions, and silence.Why is the tumor microenvironment immunosuppressive? ›
Tumor microenvironment is a barrier to effector immune cells
Dysregulated cancer cell growth can lead to tumor intrinsic immunosuppressive features, such as regions of hypoxia and elevated levels of lactate that can inhibit effector T cell function.
The primary tumor microenvironment. The cellular component of TME includes cancer and noncancerous cells, immune cells, mesenchymal stem cells, endothelial cells, niche cells, cancer-associated fibroblasts, and adipocytes that can promote tumor growth .
These cells shape the tumor microenvironment in four main ways: tumor proliferation and metastasis, neoangiogenesis, extracellular matrix remodeling and immunosuppression.What are three 3 environmental causes of cancer? ›
However, exposures to certain chemicals in the environment, at home, and at work may contribute to an individual's risk of developing cancer. Benzene, asbestos, vinyl chloride, radon, and arsenic are examples of toxic substances that can increase the risk of cancer to those who are exposed.What two environmental factors are most frequently associated with the development of cancer? ›
These exposures may include substances, such as the chemicals in tobacco smoke, or radiation, such as ultraviolet rays from the sun. People can avoid some cancer-causing exposures, such as tobacco smoke and the sun's rays.Is breast cancer driven by environmental factors? ›
Although we know of many risk factors that increase women's chances of developing breast cancer, scientists do not completely understand what causes normal cells to become cancerous. But most experts agree that a combination of genetic, hormonal, and environmental factors leads to breast cancer.What is the breast cancer environmental movement? ›
In the early 1980s, the burgeoning environmental breast cancer movement (EBCM) began to take hold, backed by increasing evidence from TLC member, Breast Cancer Action, the first health organization and feminist health alliance to link the disease to environmental causes.How much of breast cancer is environmental? ›
More than 90% of cases are thought to be caused by environmental factors, i.e. external biological, physical or chemical factors. After much research, today we know some of the factors that can affect the development of this type of cancer.Can signaling pathways lead to breast cancer? ›
One of the signaling pathways upregulated in aggressive subtype of breast cancer is the hedgehog signaling pathway (61). There is an association between overexpression of hedgehog signaling pathway regulators such as SHH, DHH, IHH, PTCH1, SMO, and GLI1 with proliferation, migration, and aggressiveness of BC (88).What is the PI3K AKT mTOR signaling pathway in breast cancer? ›
PI3K/Akt/mTOR signaling pathway involved in cell survival, growth, and proliferation is the commonly activated signaling pathway in human cancers. Dysregulated mTOR activation is a frequent observation in cancer and represents a process in cancerogenesis.What is the signalling pathway of HER2 positive breast cancer? ›
HER2 signaling pathway
HER2 subtype of breast cancer is associated with gene amplification and/or protein overexpression of Human epidermal growth factor receptor 2 (HER2/neu), also known as ErbB2 which leads to aggressive tumor growth and poor clinical outcome. HER2 belongs to HER family of receptor tyrosine kinase.
Normal breast development and mammary stem cells are regulated by several signaling pathways, such as estrogen receptors (ERs), HER2, and Wnt/β-catenin signaling pathways, which control stem cell proliferation, cell death, cell differentiation, and cell motility.
The two RAS signaling pathways most prominently associated with cancer are the MAP kinase pathway regulating cell proliferation and the phosphoinositide 3-kinase (PI3K) pathway that regulates cell metabolism and survival (Figure 1).What are the key signaling pathways implicated in cell cycle control in cancer? ›
The Ras-ERK and PI3K pathways. Oncogenic mutations, amplification, or gene fusions involving upstream tyrosine kinases lead to constitutive signaling through both the Ras-ERK and PI3K-Akt pathways.Are signalling pathways disrupted in cancer? ›
It is clear that a signaling pathway can be disrupted at multiple points, and a variety of genomic and epigenomic alterations can contribute to this, ultimately leading to cancer.What is PI3K pathway in cancers? ›
The PI3K/AKT signaling pathway regulates cell survival and proliferation. Aberrant activation of the pathway is commonly observed in many human cancers, including breast, lung, ovarian, and prostate. Increased activity of this pathway is often associated with tumor progression and resistance to cancer therapies.What is the role of PI3K-akt mTOR pathway in cancer? ›
The PI3K/Akt/mTOR pathway regulates cell proliferation, growth, cell size, metabolism, and motility. Component genes of this pathway have been extensively studied and found to be commonly activated in human cancer.Is Akt a therapeutic target for cancer? ›
The abnormal overexpression or activation of AKT has been observed in many cancers, including ovarian, lung, and pancreatic cancers, and is associated with increased cancer cell proliferation and survival. Therefore, targeting AKT could provide an important approach for cancer prevention and therapy.Where does HER2-positive breast cancer spread first? ›
Usually in HER2-positive metastatic breast cancer, common places of spread include the liver, lung, bones, lymph nodes, and unfortunately the brain.How does Herceptin target HER2? ›
How does trastuzumab work? Trastuzumab is an antibody drug specially made to target HER2-positive cancer cells. Trastuzumab attaches to the HER2 protein on the surface of HER2-positive breast cancer cells. This can slow or stop their growth.