Panitumumab

effect of panitumumab
Brand name: Vectibix®
FDA approval: Yes
Usage:

Vectibix is classified as a monoclonalDerived from a single source. In the context of cancer, the term is used in two ways: 1) to refer to the fact that tumors arise from a single damaged cell and 2) to describe the antibodies used in the treatment of cancer. antibodyAntibody molecules tightly bind to their targets (usually proteins) with great specificity. Antibody binding alerts the immune system to target the bound molecule for destruction. Specific antibodies can be made in the laboratory. and signal transduction inhibitor by binding to epidermal growth factorA substance that stimulates cell division. Growth factors are usually small proteins or steroid hormones. They may be secreted by the same cells on which they act or by cells that reside in a different part of the body than the target cells. Some examples of growth factors include estrogen, a growth factor for breast cells, and VEGF, a growth factor that causes the development of blood vessels. Several different anti-cancer treatments are designed to inhibit the activity of growth factors. receptors (EGFR). Vectibix is used to treat colorectal cancer that has spread.  It is used to treat colon cancers that express EGFR and disease that has gotten worse either on or following fluoropyrimidine, oxaliplatin and irinotecan containing chemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division. regimens.  

Vectibix is injected into a vein through an IV. A healthcare provider will give you this injection. Before you receive this medicine, you may need to undergo a biopsyA medical procedure in which a sample of tissue is removed for examination. Biopsies can range from a small sample drawn into a needle to samples taken during more invasive surgery. to make sure panitumumab is the right medication to treat your cancer. Vectibix must be given slowly, and the IV infusion can take up to 90 minutes to complete. Vectibix is usually given once every 2 weeks. Follow your doctor's instructions. While using panitumumab, you may need frequent blood tests. Your skin and vision may also need to be checked. Panitumumab can have long lasting effects on your body. You may need frequent medical tests for up to 8 weeks after you stop using this medicine.

Mechanism:

The EGFR is a transmembrane glycoproteinA protein that has been modified by the addition of one or more sugar molecules (carbohydrates). The addition of the sugar molecules alters the properties/function of the protein. Many proteins located on the outside of cell membranes are glycoproteins. that is a member of a subfamily of type I receptor tyrosine kinases, including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in normal epithelialA type of tissue (epithelium) that covers our exposed surfaces, such as skin. Also lines our hollow or tube-like organs/tissues such as the digestive tract. Since these tissues are often exposed to environmental insults such as chemicals and solar radiation and are often divide rapidly to replace lost cells, many cancers arise in epithelial tissues. tissues, including the skin and hair follicle. EGFR is overexpressed in certain human cancers, including colon and rectum cancers. Interaction of EGFR with its normal ligands (eg, EGF, transforming growth factorA substance that stimulates cell division. Growth factors are usually small proteins or steroid hormones. They may be secreted by the same cells on which they act or by cells that reside in a different part of the body than the target cells. Some examples of growth factors include estrogen, a growth factor for breast cells, and VEGF, a growth factor that causes the development of blood vessels. Several different anti-cancer treatments are designed to inhibit the activity of growth factors.-alpha) leads to phosphorylationThe addition of a phosphate group to a metabolic intermediate or to a protein. The addition or removal (dephosphorylation) of phosphate groups acts as a biological on/off switch for many processes. Addition or removal of a phosphate group can activate/inactivate an enzyme and control processes such as cell division. Enyzmes that add phosphate groups are termed kinases and those that remove phosphate groups are called phosphatases. and activation of a series of intracellular proteins, which in turn regulate transcriptionThe production of an RNA molecule from a DNA template. An RNA copy of a gene is produced by an enzyme, RNA polymerase. The RNA produced can either be used directly in the cell or can be used to direct the production of a protein through the process of translation. Many of the genes that are altered in cancer cells have potent effects on the process of transcription. See transcription factor. of genes involved with cellular growth and survival, motility, and proliferationRefers to cell division. The proliferation rate is an indicator of how quickly a tumor is growing. The proliferation rate may be represented as a percentage, showing what fraction of the cells are actively involved in the division process.. Signal transduction through the EGFR results in activation of the wild-type KRAS proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins.. However, in cells with activating KRAS somatic mutations, the KRAS-mutant protein is continuously active and appears independent of EGFR regulation. 

Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosisAlso called programmed cell death. Apoptosis is a natural process that occurs throughout the lives of almost all animals and plants. The death of the cells is a carefully controlled process that does not generate any inflammation., decreased proinflammatory cytokine and vascular growth factor production, and internalization of the EGFR. In vitroFrom the Latin, assays and in vivo animal studies demonstrate that panitumumab inhibits the growth and survival of selected human tumor cell lines expressing EGFR. 

The diagram below shows the 3D molecular structure of Panitumumab in complex with epidermal growth factor receptor domain 3.

Side effects:

Some people receiving a Vectibix injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, nauseated, light-headed, or have a fever, chills, chest tightness, or trouble breathing during the injection. Common Vectibix side effects may include: acne, dry skin, rash, itching; swelling or irritation around your fingernails or toenails; loss of appetite, nausea, diarrhea; blisters or ulcers in your mouth, red or swollen gums, trouble swallowing; tired feeling, weakness; or low potassium - confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling.

Contraindications:

Serious effects that can result from panitumumab treatment include dermatologic toxicity including dermatitis acneiform, redness, paronychia (infection at the base of the fingernail or toenail), rash, skin exfoliation, dry skin and skin fissures; infusion reactions (anaphylactic shock, bronchospasm, fever, chills and low blood pressure); and pulmonary fibrosis. Due to a potential harm to the developing fetus, women receiving this treatment should take contraceptive measures and pregnant women should be warned of this risk. New mothers should not nurse infants during or immediately following this treatment regimen. Panitumumab is not recommended for use in combination chemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division. regimens. Since sunlight can enhance skin reactions due to panitumumab, patients should limit sun exposure during treatment.1

  • 1.Chu, E., & DeVita, V. T. (2015). Physicians' cancer chemotherapy drug manual 2015. Burlington, MA: Jones & Bartlett Learning.