Cancer metastases: tumor spread

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Cancer metastases: tumor spread

Section 1: Basics of metastasis

1.1 What are metastases?

Metastases are the process of spreading cancer cells from the primary tumor to other parts of the body. This is a key feature of cancer that makes it deadly. Unlike localized tumors that can be removed surgically or treated with local methods (for example, radiation therapy), metastatic cancer requires systemic treatment that affects the entire organism.

Metastases are formed when cancer cells come off the primary tumor, penetrate into the bloodstone or lymph vessels and spread throughout the body. They can settle in new organs or tissues and begin to form secondary tumors. These secondary tumors are called metastatic tumors or metastases. They consist of the same types of cells as the primary tumor, and therefore are classified as cancer of primary origin (for example, breast cancer metastases are not lung cancer, but metastatic cancer of the mammary gland).

1.2 metastasis mechanisms: cascade of events

Metastasis is a complex and multi -stage process, which is often described as a “metastatic cascade.” This cascade consists of several consistent stages, each of which requires certain abilities from cancer cells:

Local invasion: Cancer cells must first separate from the primary tumor and invade the surrounding fabrics. This includes the destruction of the extracellular matrix (VKM), a complex network of molecules that surrounds and supports cells. Cancer cells secrete enzymes, such as metalloproteinase matrix (MMP), which destroy VKM, allowing them to move. Changes in adhesive molecules, such as cadgerines, also play a role. In healthy tissues, cadgerines glue cells together. With cancer, there is often a decrease in the expression of cadgerins, which facilitates the separation of cells from the tumor.
Intravascular invasion (intravation): After the invasion of the surrounding tissues, cancer cells should penetrate the bloodstone or lymph vessels. This process is called intravasation. It is believed that it is facilitated by chemotaxis, i.e., cell movement in response to chemical signals. Cancer cells can secrete factors that attract endothelial cells lining blood vessels, or they can respond to factors secreted by stromal cells (cells that support tissues) in tumor micro -infection.
Survival in blood flow/lymph flow: Once in the bloodstream or lymph flow, cancer cells face severe conditions. They are exposed to shift forces, attack immune cells and compete for nutrients. Only a small part of the cancer cells that have penetrated the bloodstream survive. To survive, cancer cells can form units with other cancer cells or platelets, which protects them from the immune system and facilitates sticking to the walls of blood vessels.
Extravation: This is the process of cancer cells from blood or lymph vessels into a new tissue or organ. Cancer cells stick to endothelial cells lining the walls of the vessels, and then penetrate through the wall of the vessel. This process often includes the same mechanisms as intravation, such as the destruction of VKM and changes in adhesive molecules.
Colonization: After extravasia, cancer cells should adapt to a new micro -infection and begin to multiply, forming a metastatic tumor. This process, called colonization, is the most ineffective stage of the metastatic cascade. Many cancer cells cannot survive in the new micro-infection due to the lack of necessary growth factors, immune attacks or other adverse conditions. For successful colonization, cancer cells must induce angiogenesis (the formation of new blood vessels) to supply a metastatic tumor with oxygen and nutrients. They must also evade immune supervision and interact with the stromal cells in a new micro -infection.

1.3 paths of metastasis:

Cancer cells can spread in several ways:

Lymphogenic path: This is the most common path of metastasis. Cancer cells penetrate the lymph vessels and move into regional lymph nodes. The lymph nodes serve as filters that delay cancer cells. If cancer cells overcome lymph nodes, they can spread to more distant lymph nodes and other organs. The defeat of the lymph nodes is an important prognostic factor for many types of cancer.
Hematogenic path: This is the spread of cancer through blood vessels. Cancer cells penetrate the veins or arteries and are transferred with blood to distant organs. The most common places of hematogenous metastasis are lungs, liver, bones and brain.
Translomic path: This is the distribution of cancer cells in the body of the body, such as pleural (lungs), peritoneal (abdominal) or pericardial (heart) cavities. This path is especially important for cancers of ovaries, stomach and colon. Cancer cells can break away from the primary tumor and swim freely in the body cavities, then settle on the surface of the organs and form secondary tumors.
Implantation: This is the distribution of cancer cells directly into neighboring tissues or organs during surgery or biopsy. Although this path is less common, it can lead to a local relapse of cancer.

1.4 Organotropism: Why does cancer metastasize in certain places?

Organotropism is a tendency of certain types of cancer to metastation into certain organs. For example, breast cancer often metastasizes in bones, lungs, liver and brain, and colon cancer in the liver and lungs. Several factors explain organotropism:

“Theory of seeds and soil”: This theory, proposed by Stephen Page, suggests that cancer cells (“seeds”) can successfully grow only in certain organs (“soils”), which provide the necessary growth factors, nutrients and micro -infection.
Hemokins and Khemokin’s receptors: Hemokins are small proteins that act as chemical signals that guide cells to certain places. Cancer cells can express the receptors of chemokins, which are associated with chemokins, secreted cells in certain organs, thereby directing cancer cells to these organs. For example, breast cancer cells often express the CXCR4 Khemokin receptor, which is associated with CXCL12 Hemokin, which are present in the bone marrow, which can explain the metastasis of breast cancer in the bone.
Adhesive molecules: Cancer cells should stick to endothelial cells lining the walls of blood vessels in order to extract to the new organ. Adhesive molecules, such as selectins and integrines, play an important role in this process. Various organs express various adhesive molecules that can specifically contact a certain type of cancer cells.
Organic micro -infection: Micro -angle of the organ, including stromal cells, extracellular matrix and immune cells, can affect the growth and survival of metastatic cells. Some organs can provide more favorable micro -infection for certain types of cancer cells.

Section 2: Factors affecting metastasis

2.1 Genetic and epigenetic changes:

Metastasis is a complex process in which many genetic and epigenetic changes in cancer cells are involved. These changes lead to the acquisition of cancer cells of the ability to invasion, migration, survival in the bloodstream and colonization of remote organs.

Mutations in the genes of tumors: Tumor-spress genes control the growth and division of cells. Mutations in these genes can lead to uncontrolled cell growth and increase the risk of metastasis. Examples of tumor-participating in metastasis genes include TP53, PTEN and RB.
Activation of oncogenes: Oncogenes are genes that contribute to the growth and division of cells. Activation of oncogenes can occur as a result of mutations, amplification of genes or translocations. Activation of oncogenes can lead to uncontrolled cell growth and increase the risk of metastasis. Examples of oncogenes involved in metastasis include RAS, MyC and HER2.
Epigenetic changes: Epigenetic changes are changes in genes expression that are not associated with changes in the DNA sequence. Epigenetic changes may include DNA methylation, histone modifications and micrord regulation. These changes can affect the expression of genes involved in metastasis. For example, DNA methylation can lead to suppression of tumor-genes, and histones modifications can affect the availability of DNA for transcription factors.
Epithelial-mechanical transition (EMP): EMP is a process in which epithelial cells, tightly connected with each other, pass into meshenchimal cells that are more mobile and invasive. EMP plays an important role in metastasis. During EMP, the cells lose intercellular contacts, change the shape and begin to secrete enzymes that destroy the extracellular matrix. EMP is regulated by various transcription factors such as Snail, Twist and ZEB.

2.2 Micro -angle of the tumor:

Micro -angle of the tumor (MOO) is a complex and dynamic environment surrounding tumor cells. It includes stromal cells (fibroblasts, endothelial cells, immune cells), extracellular matrix (VKM), growth factors, cytokines and blood vessels. MOO plays an important role in the growth of the tumor, angiogenesis, invasion and metastasis.

Stromal cells: Stromal cells can have both stimulating and inhibitory effects on the growth and metastasis of the tumor. For example, fibroblasts associated with cancer (headlights) can secrete growth factors and cytokines that contribute to the growth of tumor and angiogenesis. On the other hand, immune cells, such as T-lymphocytes, can kill cancer cells and suppress metastasis.
Extracellular matrix (VKM): VKM is a complex network of molecules that surrounds and supports cells. VKM consists of collagen, laminin, fibronectin and other glycoproteins. VKM can influence the growth of a tumor, invasion and metastasis. For example, a change in the composition of the VKM can contribute to the invasion of cancer cells.
Growth factors and cytokines: Growth factors and cytokines are small proteins that act as chemical signals that regulate the growth, division and differentiation of cells. MOO contains many growth factors and cytokines that can affect the growth of tumor and metastasis. For example, the vascular endothelium factor (VEGF) contributes to angiogenesis, and the transforming factor of beta growth (TGF-β) can contribute to the EMP.
Angiogenes: Angiogenesis is the formation of new blood vessels. Tumors need angiogenesis to supply oxygen and nutrients. Angiogenesis can also contribute to metastasis, since new blood vessels serve by the spread of cancer cells into remote organs.

2.3 The role of the immune system:

The immune system plays a complex role in the control of cancer, exerting both antitumor and frail effects. On the one hand, immune cells, such as T-lymphocytes and NK cells, can recognize and kill cancer cells. On the other hand, some immune cells can contribute to tumor growth and metastasis.

Immune supervision: The concept of immune supervision suggests that the immune system constantly monitors the body for abnormal cells, including cancer cells, and destroys them. However, cancer cells can develop mechanisms for evasion from immune supervision, allowing them to survive and grow.
Immunosuppression: Tumors can create immunosuppressive micro -inflection that overwhelm the activity of immune cells. This can happen by secretion of immunosuppressive cytokines, such as TGF-β and IL-10, or by attracting regulatory T-lymphocytes (Treg), which inhibit the activity of other immune cells.
Inflammation: Chronic inflammation can contribute to the growth of the tumor and metastasis. Inflammation can lead to damage to DNA, angiogenesis and immunosuppression. Some immune cells, such as macrophages, can secrete growth factors and cytokines that contribute to the growth of the tumor.
Immunotherapy: Immunotherapy is a type of cancer treatment that uses the immune system to combat cancer. Immunotherapy may include the use of control points of the immune response, such as anti-PD-1 and anti-CTLA-4, which block the mechanisms used by cancer cells to evade immune supervision.

2.4 The influence of hormones and growth factors:

Hormones and growth factors play an important role in the regulation of cell growth and development, including cancer cells. Some types of cancer, such as breast cancer and prostate cancer, are hormone -dependent, which means that their growth is stimulated by hormones.

Breast cancer: Breast cancer can be positive in terms of estrogen receptors (ER+) or progesterone (PR+). Estrogen and progesterone are hormones that stimulate the growth of breast cells. Hormonal therapy, such as tamoxifen and aromatase inhibitors, is used to block the action of estrogen and progesterone and suppress growth ER+ and PR+ breast cancer.
Prostate cancer: Prostate cancer is hormone -dependent and is stimulated by androgens such as testosterone. Androgenic deprivation therapy (ADT), which reduces the level of androgens in the body, is the main method of treating prostate cancer.
Growth factors: Growth factors, such as an epidermal growth factor (EGF) and a hepatocyte growth factor (HGF), can stimulate tumor growth and metastasis. Some types of cancer, such as lung cancer and colon cancer, have mutations in genes encoding growth receptors, which leads to their excessive activity. Inhibitors of growth factors, such as Gephitinib and Cetuximab, are used to block the action of growth factors and suppress tumor growth.

Section 3: Diagnostics and Monitoring of Metastases

3.1 Visualization methods:

Visualization methods play a decisive role in the diagnosis and monitoring of metastases. They allow doctors to detect and evaluate the size, localization and amount of metastatic tumors.

Computed tomography (CT): CT uses x -rays to create detailed images of internal organs and tissues. CT can be used to detect metastases in lungs, liver, bones and other organs. CT is often used with contrast agent to improve tumors visualization.
Magnetic resonance tomography (MRI): MRI uses a magnetic field and radio waves to create images of internal organs and tissues. MRI provides more detailed images of soft tissues than CT, and is especially useful for detecting metastases in the brain, spine and liver.
Positron emission tomography (PET): PET uses a radioactive tracer that is inserted into the body and absorbed by cells. PET can detect metabolically active cells, including cancer cells. PET is often used in combination with CT (PET-KT) to improve tumor localization.
Bones scintigraphy: Bones scintigraphy uses a radioactive tracer that is absorbed by bones. Bone scintigraphy can be used to detect metastases in bones.
Ultrasound examination (ultrasound): Ultrasound uses sound waves to create images of internal organs. Ultrasound can be used to detect metastases in the liver, lymph nodes and other organs.

3.2 Biopsy:

A biopsy is a procedure in which a sample of tissue is taken for research under a microscope. The biopsy is the gold standard for the diagnosis of cancer and determine its type and stage. The biopsy of the metastatic tumor can be used to confirm the diagnosis of metastatic cancer and determine its characteristics, such as hormone and Her2 receptors expression.

3.3 blood tests: tumor markers and circulating tumor cells (TsOC):

Blood tests can be used to monitor the progression of cancer and assess the response to treatment.

Tumor markers: Tumor markers are substances that are produced by cancer cells and can be found in the blood. The level of tumor markers can increase in the presence of cancer. Examples of tumor markers include PSA (prostate cancer), CA-125 (ovarian cancer) and CEA (colon cancer). However, tumor markers are not always specific for cancer and can be increased in other conditions.
Circulating tumor cells (TsOC): Tsok is cancer cells that separated from the primary tumor and circulate in the bloodstream. The detection of TsOC in the blood may indicate the presence of metastatic cancer. Calculation of TsOC can be used to monitor the progression of cancer and evaluate the response to treatment.

3.4 molecular tumor profiling:

The molecular profiling of the tumor includes an analysis of DNA, RNA and proteins of tumor cells to detect genetic and molecular abnormalities, which can be a target for treatment. Molecular tumor profiling can be used to select the most effective treatment for each specific patient. Examples of molecular tumor profiling include a new generation sequencing (NGS) and immunohymia (IGC).

Section 4: Treatment of metastatic cancer

4.1 Surgical treatment:

Surgical treatment of metastatic cancer may be an option in some cases, especially if metastases are localized and can be removed with minimal risk. Surgical removal of metastases can improve the survival and quality of life of some patients. For example, surgical removal of metastases of the colon cancer in the liver or lungs can be effective.

4.2 radiation therapy:

Radiation therapy uses high -energy X -rays or other types of radiation to destroy cancer cells. Radiation therapy can be used to treat metastases in various organs, such as bones, brain and lungs. Radiation therapy can help relieve pain, reduce symptoms and improve the quality of life.

Stereotactic radiation therapy (SLT): SLT is a type of radiation therapy that uses high -precision radiation rays for aiming on a tumor. SLT can be used to treat small metastases in the brain, lungs and other organs.

4.3 System therapy:

System therapy is a type of treatment that affects cancer cells throughout the body. System therapy includes chemotherapy, hormonal therapy, targeted therapy and immunotherapy.

Chemotherapy: Chemotherapy uses drugs to destroy cancer cells. Chemotherapy can be used to treat metastatic cancer in various organs. Chemotherapy often causes side effects, such as nausea, vomiting, hair loss and fatigue.
Hormonal therapy: Hormone therapy is used to treat hormone -dependent cancers, such as breast cancer and prostate cancer. Hormone therapy can block the effect of hormones that stimulate the growth of cancer cells.
Target therapy: Targeted therapy uses drugs for aiming on specific molecules or paths involved in the growth and spread of cancer cells. Targeted therapy can be more effective and have less side effects than chemotherapy. Examples of targeted therapy include tyrosinkinase inhibitors (ITK) and BRAF inhibitors.
Immunotherapy: Immunotherapy uses the immune system to combat cancer. Immunotherapy may include the use of control points of the immune response, such as anti-PD-1 and anti-CTLA-4, which block the mechanisms used by cancer cells to evade immune supervision. Immunotherapy can have serious side effects, such as autoimmune reactions.

4.4 Palliative treatment:

Palliative treatment is aimed at alleviating symptoms and improving the quality of life of patients with metastatic cancer. Palliative treatment may include anesthesia, management of symptoms, such as nausea and fatigue, and psychological support.

Section 5: Forecast and survival with metastatic cancer

5.1 Factors affecting the forecast:

The prognosis for metastatic cancer depends on many factors, including:

Cancer type: Some types of cancer have a more aggressive course and worst forecast than others.
Cancer stage: The stage of cancer when making a diagnosis is an important factor. Early detection and treatment can improve the prognosis.
Localization of metastases: Localization of metastases can affect the forecast. For example, metastases in the brain are often associated with the worst forecast.
Age and general health of the patient: Young and more healthy patients often have the best prognosis.
Answer to treatment: The response to treatment is an important factor. Patients who respond well to treatment often have the best prognosis.
Molecular characteristics of the tumor: The molecular characteristics of the tumor, such as the presence of certain mutations, can affect the forecast.

5.2 survival statistics:

The statistics of survival in metastatic cancer varies depending on the type of cancer, cancer, localization of metastases and other factors. Survival statistics are an assessment of the percentage of patients who are alive after a certain period of time after the diagnosis. It is important to remember that survival statistics are only average indicators and cannot predict an individual forecast for a particular patient.

Section 6: New directions in metastases research

6.1 liquid biopsy:

Liquid biopsy is a non -invasive method that allows you to analyze cancer cells or DNA circulating in the blood. Liquid biopsy can be used for early diagnosis of cancer, monitoring cancer progression and evaluate the response to treatment. Liquid biopsy has a potential for revolutionizing cancer treatment, allowing doctors to receive information about cancer in real time without the need to conduct invasive biopsy.

6.2 Immunotherapy:

Immunotherapy is a promising new approach to the treatment of metastatic cancer. Inhibitors of control points of the immune response, such as anti-PD-1 and anti-CTLA-4, showed promising results in the treatment of various types of cancer, including melanoma, lung cancer and kidney cancer. Other types of immunotherapy, such as Car-T cell therapy and therapy with oncolytic viruses, are also under development.

6.3 targeted therapy:

The development of new targeted drugs aimed at specific molecules and paths involved in metastasis is an active field of research. Examples of new targeted drugs include MMP inhibitors, EMP inhibitors and angiogenesis inhibitors.

6.4 Nanotechnologies:

Nanotechnologies are used to develop new methods of diagnosis and treatment of metastatic cancer. Nanoparticles can be used to deliver drugs directly to cancer cells, to improve tumor visualization and to destroy cancer cells with heat or light.

6.5 Cancer metabolism:

Studies of cancer metabolism are aimed at understanding metabolic changes occurring in cancer cells. Cancer cells often have an abnormal metabolism, which allows them to grow quickly and share. Understanding the metabolism of cancer can lead to the development of new cancer treatment strategies aimed at the metabolic pathways necessary for the survival of cancer cells.

Section 7: Life with metastatic cancer

7.1 Psychological support:

The diagnosis of metastatic cancer can be destructive and cause severe stress, anxiety and depression. It is important to get psychological support from family, friends, specialists in mental health and support groups.

7.2 Physical activity and nutrition:

Physical activity and healthy nutrition can help improve the quality of life of patients with metastatic cancer. Physical activity can help reduce fatigue, improve mood and strengthen the immune system. Healthy nutrition can help maintain weight, provide the body with the necessary nutrients and reduce the side effects of treatment.

7.3 Symptoms management:

Management of symptoms, such as pain, nausea, fatigue and loss of appetite, is an important part of patients with metastatic cancer. There are various treatment methods that can help alleviate the symptoms and improve the quality of life.

7.4 Communication with doctors and family:

Open and honest communication with doctors and family is crucial for controlling metastatic cancer. It is important to ask questions, share your fears and take an active part in making decisions on treatment.

7.5 Planning of the future:

Planning the future, including financial planning, legal planning and care planning, can help patients with metastatic cancer feel more controlled and reduced stress.

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