Signaling pathways in breast cancer: therapeutic targeting of the microenvironment (2023)

FAQs

What are the signaling pathways involved in breast cancer? ›

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.

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.

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.

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.

There are four basic categories of chemical signaling found in multicellular organisms: paracrine signaling, autocrine signaling, endocrine signaling, and signaling by direct contact.

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).

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.

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.

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.

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.

How does tumor microenvironment work? ›

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.

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.

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.

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.

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.

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.

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.

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.

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.

What are the 3 therapeutic approach to malignancy? ›

Common adjuvant therapies include chemotherapy, radiation therapy and hormone therapy.

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.

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.

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.

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.

The key elements of a therapeutic relationship include unconditional acceptance, empathy, genuineness, attending and listening, open-ended questions, and silence.

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 [8].

What are the types of tumor microenvironment? ›

These cells shape the tumor microenvironment in four main ways: tumor proliferation and metastasis, neoangiogenesis, extracellular matrix remodeling and immunosuppression.

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.

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.

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.

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.

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.

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).

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.

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.

Which signal transduction pathway leads to cancer? ›

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).

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.

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.

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.

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.

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.

Usually in HER2-positive metastatic breast cancer, common places of spread include the liver, lung, bones, lymph nodes, and unfortunately the brain.

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.