ONS/ONCC Chemotherapy/Immunotherapy Lesson 11: Targeted Therapies fully solved 2024

How targeted therapy and chemo differ -targeted therapies act on specific molecular targets on or within the cells that are associated with cancer, whereas standard chemo act on all rapidly dividing cells-chemo has more SEs-targeted therapy ae chosen and designed to interact with their target on or within the cells, whereas chemo were IDed becaused they kill cells-targeted therapies are often cytostatic (they block tumor cell proliferation) whereas chemo agents are cytotoxic (kill tumor cells) Goals of targeted therapy -disease cure when used as primary or adjuvant therapy -improving overall response or increase disease-free survival when used in combination with conventional therapies -controlling or stabilizing disease -maintaining or enhancing quality of life -decreasing the severity of toxicities from other therapies Ligand a substance that forms a complex with another biomolecule to exert a biologic effect Ligand Binding process by which the ligand attaches to a specific receptor site and activates that receptor, activating the signaling pathway Dimerization two monomers that are side-by-side on the surface of the cell are paired and activated by a ligand, which causes a series of signals Kinase type of enzyme that adds chemicals called phosphates to other molecules such as sugars or proteins causing other molecules in the cell to become either active or inactive phosphorylation activation of a chemical process to initiate signaling targeted therapies work by doing the following 1. blocking angiogenesis 2. blocking signals inside or outside the cell 3. delivering toxic substances to the cell 4. stimulating the body's immune system BCR/ABL -fusion protein tyrosine kinase formed with a gene translocation occurs between gene 9 and 22-gene abnormality called the Philadelphia chromosome seen in CML and ALL VEGF this is the primary angiogenic factor produced by cells mTOR -target of rapamycin-a protein that tells cells when to grow, divide, and survive Two ways that angiogenesis inhibitors work 1. some intergere with action of VEGF which stimulates n ew blood vessel formation2. others target their molecules that stimulate new blood vessel growth Small Molecule Compound Targeted Therapies -end in -ib-targets located inside the cell because these gents are able to enter cells more easily-intracellular-most given orally Monoclonal Antibody Targeted Therapy - end in -mab-relatively large in size and therefore usually cannot enter cells-extracellular or transmembrane-man made version of antibodies that are designed to attack a very specific target on cancer cells-usually from mice Targeted Therapy NCI definition a type of treatment that uses drugs or other substances to identify/attack specific types of cancer cells with less harm to normal cells. Some therapies block the action of certain enzymes, proteins, or other molecules in growth/spread of cancer cells. Other therapies work with immune system to kill cancer cells/deliver toxic substances directly to cancer cell and kill them Receptor molecule inside/on surface of cell that binds to specific substance and causes a specific effect in cell Monomer molecule that can join with other identical monomers to form larger structure called polymer Signaling Pathway (also signaling cascade) chain of events that occurs in the cytoplasm of the cell to propagate the signal from the plasma membrane to produce a response Targets of targeted therapy -Extracellular -Intracellular -transmembrane Extracellular target receptors on the outside of the cell Intracellular target/interfere with processes inside the cell -interrupt signalling cascade within the cell Transmembrane environment within the surface of the cell Target therapy affects the ability of the cancer cell to... -grow -divide -repair -communicate Molecular targets -tumor cell receptors -angiogenesis/endothelial cell ligands and receptors -signal transduction pathway -apoptosis/enzyme complex -tumor specific antigens -multitargets Signal transduction inhibitors -block signal transduction (process by which a cell responds to signals from environment) -interfere with inappropriate signalling (blocking cell signals can sometimes help keep cancer under control) cell signaling process 1. cell receives specific signal 2. signal is transmitted by proteins to cells control center through series of biochemical reactions 3. control center reads signals and produces appropriate response Activation of tyrosine kinase triggers... biochemical cascade of cell-signaling Biochemical cascade of cell-signalling process 1. cell proliferation 2. induction of angiogenesis 3. increased growth factor production 4. inhibit apoptosis In cancer cells, signals are always... ON -malignant cells stimulated to continue cell division Examples of Signal Transduction Inhibitors -EGFR inhibitors -HER2 inhibitors -ALK inhibitors -BCR-ABL inhibitors -BRAF Kinase inhibitors (multikinase inhibitors) HER family -HER2 first of HER family to be specifically targeted; activated by overexpression and amplification -HER1 (EGFR or erb1 receptor); growth factors