What is cancer targeted therapy?
Targeted antiangiogenic therapies inhibit the formation of new blood vessels in cancerous tumors by blocking the factors that promote angiogenesis (the scientific name for growing blood vessels).
Targeted cancer therapies are specialized treatments focusing on specific factors that promote cancer growth and spread (metastasis). Targeted therapies involve administration of medications that interfere with the activity of proteins and cell-signaling mechanisms that cause cancer cells to develop, and help in their continued survival and proliferation.
How do cancers grow?
Cancers are a large group of diseases caused by uncontrolled growth of abnormal cells which breach the growth regulatory mechanisms in the body. Cancers arise due to genetic mutations in the cells which occur due to hereditary or environmental factors, certain viral infections, and sometimes for no identifiable reason.
Normal cells follow a strictly regulated cell cycle that instructs them to grow, divide, differentiate into a cell with specific function, or die, at the appropriate time. Normal cells undergo programmed cell death (apoptosis) when they are infected, old, damaged or simply no longer needed.
The defect in the cancer cell’s DNA activates genes that instruct the cancer cells to grow and divide endlessly, evading death. Continued growth of cancer cells can form abnormal lumps of tissue known as tumors. Tumors are termed to be malignant when tumor cells migrate to other parts of the body and metastasize.
Tumors cannot grow beyond a certain size without continued supply of oxygen and nutrients. In order to sustain their growth and metastasis, tumor cells develop the ability to subvert normal body mechanisms that keep one healthy.
One of the important mechanisms crucial for the tumor’s growth, survival and metastasis is the generation of new blood vessels (angiogenesis) that can meet its continuously increasing need for oxygen and nutrients.
How do cancer cells stimulate angiogenesis?
In healthy tissue, angiogenesis is an essential process for growth and development, as well as wound healing and growing new healthy tissue.
Angiogenesis is also the way tumors grow their own blood vessels to supply themselves with oxygen and nutrients -- like an invading army taking control of your country’s highway and electrical systems to further their goal of conquest.
Angiogenesis is a complex system regulated by proangiogenic and antiangiogenic factors. Angiogenesis involves migration, growth and differentiation of endothelial cells (cells lining the inside walls of blood vessels).
Tumor cells secrete enzymes that stimulate proangiogenic factors. Tumor cells can also stimulate the neighboring normal cells to produce proangiogenic signals and aid the tumor angiogenesis.
What are targeted antiangiogenic therapies?
Targeted antiangiogenic therapies inhibit the formation of new blood vessels in tumors by blocking the factors that promote angiogenesis. Targeted antiangiogenic therapies come in two forms:
- Small molecule drugs: Microscopic molecules that can work on the cell surface or get right inside the cell to interfere with the cellular processes.
- Monoclonal antibodies: Lab-produced cancer-specific antibodies that are too large to get inside a cell, but work by attaching to protein receptors on the cell surface, thus signaling the body’s immune system to kill them.
Following are the targeted therapies with angiogenesis inhibitors:
Vascular endothelial growth factor (VEGF) family consists of six types of glycoproteins (VEGF A, B, C, D, E and placental growth factor) which cells secrete to stimulate angiogenesis. The VEGF molecules bind to VEGF receptors in endothelial cells and stimulate them to form new blood vessels. There are three types of VEGF receptors, VEGFR1, 2 and 3.
VEGF-targeted therapies have been developed as monotherapy or for administration along with chemotherapy. Many monoclonal antibodies and small molecule drugs that target this pathway are in clinical trials. Cancers can, however, develop resistance to medications.
The FDA-approved therapies that target VEGF are:
- Bevacizumab (Avastin)
- Bevacizumab-awwb (Mvasi)
Both are monoclonal antibodies approved for the treatment of:
- Metastatic colorectal cancer
- Non-small-cell lung cancer
- Brain cancer (glioblastoma)
- Metastatic renal cell carcinoma
- Metastatic cervical cancer
- Ovarian cancer
Angiopoietins are growth factors secreted by cells to promote angiogenesis from pre-existing blood vessels. Four angiopoietins have been identified (Ang1 to Ang4), and Ang1 and Ang2 are required for the formation of mature blood vessels. Angiopoietins bind to protein molecules known as Tie receptors on the endothelial cells and activate them.
Currently there are no FDA-approved angiopoietin/Tie receptor targeted therapies, though many are in clinical trials.
Fibroblast growth factor (FGF) and FGF receptors play an important role in neo-angiogenesis, proliferation and stem cell survival. Fibroblasts are connective tissue cells which make up the extracellular matrix, which provides structural support to keep the cells in their natural positions.
FGFR inhibitors are in early phases of clinical trials.
The Notch signaling pathway plays a major role in embryonic vascular development and sprouting and branching of new blood vessels in angiogenesis. Targeted therapies to inhibit the Notch signaling pathways are in early phases of clinical trials.
Integrin targeted agents
Integrins are protein receptors on cell surfaces which attach the cell to the extracellular matrix. Integrins enable two-way interactions between the cell’s cytoskeleton and the extracellular matrix. Cytoskeleton is a network of microfilaments and microtubules which help the cell maintain its shape and organize the cellular components.
Integrins are necessary for vascular proliferation, adhesion, immune response, and wound repair. Many tumors are found to have excessive presence of integrins. Integrin targeted therapies are in clinical trials.
Vascular targeting agents
While antiangiogenic therapies prevent formation of new blood vessels, vascular targeting agents damage existing blood vessels in solid tumors and deprive them of blood supply.
Vascular targeting agents are designed to locally interrupt the cytoskeleton and cell-cell interactions in the endothelial cells in solid tumors. This leads to plasma leak, viscous blood flow and clot formation which block the supply of oxygen and nutrients to the tumor.
Currently there are seven small molecule vascular targeting agents in phase II clinical trials and several in preclinical development.
Targeted antiangiogenic therapies inhibit the formation of new blood vessels in cancerous tumors by blocking the factors that promote angiogenesis (the name for blood vessel formation). Targeted cancer therapies are specialized treatments focusing on specific factors that promote cancer growth and spread (metastasis).
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Cancer Risk Factors
Though it's difficult to say why some people develop cancer while others don't, research shows that certain risk factors increase a person's odds of developing cancer. These risk factors include growing older, family history of cancer, diet, alcohol and tobacco use, and exposure to sunlight, ionizing radiation, certain chemicals, and some viruses and bacteria.
Cancer is a disease caused by an abnormal growth of cells, also called malignancy. It is a group of 100 different diseases, and is not contagious. Cancer can be treated through chemotherapy, a treatment of drugs that destroy cancer cells.
Certain behavioral, lifestyle, and environmental factors contribute to cancer. Cancer prevention involves modifying these factors to decrease cancer risk. Tobacco use, alcohol consumption, physical inactivity, inadequate fruit and vegetable intake, and obesity increase the risk of certain cancers. Vaccines, genetic testing, and cancer screening also play a role in cancer prevention.
Cancer pain results from the tumor pressing on nerves or invading bones or organs. Cancer treatments like chemotherapy, radiation, or surgery can also cause pain. Over-the-counter pain relievers, prescription medications, radiation, biofeedback, and relaxation techniques are just some treatments for cancer pain.
Cancer fatigue is a lack of energy that is caused by cancer or cancer treatment, including chemotherapy, radiation, biological therapy, or bone marrow transplantation. Strategies to combat cancer fatigue include scheduling rest, pacing oneself, planning ahead and prioritizing work and activities, eating the right foods, exercising, and practicing proper body mechanics.
Tumor grade is a system used to classify cancer cells in how likely the tumor is to grow and how abnormal they look under a microscope. Tumor grade is not the same as tumor stage. A biopsy is taken to determine if the tumor is benign (non cancerous) or malignant (cancerous).
What Exactly Is a Tumor?
A tumor is an abnormal growth of cells, which serves no purpose in the body. There are three types of tumors, but it is not always clear how a tumor will develop in the future. Some non-cancerous tumors can become cancerous. Early detection of a lump or tumor is important to determine what will be the treatment.
What Is Usually the First Symptom of Testicular Cancer?
The first signs and symptoms of testicular cancer are a painless lump in the testicular area, unusual firmness in the affected testis or dull aching in the scrotum or the groin.
Which Is the Deadliest Cancer?
Lung cancer is considered to be the most deadly cancer. More people die from lung cancer each year than from breast, colorectal and prostate cancer combined.
What Type of Cancer Makes You Very Tired?
Extreme and recurrent tiredness is one of the common symptoms of most types of cancers. Tiredness is usually considered a warning sign of cancer progressing. Tiredness related to cancers usually does not get better with adequate rest or sleep.
What Is a Grade 4 Tumor?
In grade 4 cancer, tumor cells look very different from the normal cells, and most likely, they have spread to distant organs. Such tumors have a poorer outlook and may need more aggressive management. Usually, tumors in grade 4 are undifferentiated and very aggressive.
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