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ONS/ONCC Chemotherapy
Immunotherapy Certificate
Lesson 1: Foundations to Set the Stage - CORRECT ANSWER ✔✔✔ Focusing on Cellular Structure and Function - CORRECT ANSWER ✔✔✔ The Normal Cell Cycle - CORRECT ANSWER ✔✔✔ -The cell cycle refers to the ordered seres of processes of DNA replication and mitosis, or cell division -Cell nucleus regulates these processes by gathering and processing complexes molecular information Interphase and Mitotic Phase - CORRECT ANSWER ✔✔✔ Cell division produces two identical cells through these two major phases During interphase: - CORRECT ANSWER ✔✔✔ Cell grows and DNA is replicated through the following three steps: 1: First growth phase (G1 or first gap) 2: Synthesis phase (S phase) 3:Mitotic Phse (M phase) First Growth Phase (G1 or first gap) - CORRECT ANSWER ✔✔✔ -cells increase in size -reproduce RNA -"quality assurance" test that the cell will be ready to synthesis DNA -Length of time is variable, can be from hours to days Synthesis Phase (S phase) - CORRECT ANSWER ✔✔✔ -DNA replicates -Results in the formation of identical pairs of DNA (chromatids)
-which are attached a t the centromere -lasts 2-10 hours Mitotic Phase (M phase) - CORRECT ANSWER ✔✔✔ -Replicated chromosomes are aligned, separated, and move into 2 new, identical daughter cells -takes about 30-60 minutes Major points of cell regulation are entry and exit from - CORRECT ANSWER ✔✔✔ - G1 checkpoint -S Phase -G2 checkpoint -M phase Restriction Point - CORRECT ANSWER ✔✔✔ -The transition from the resting phase into an actively dividing phase (G0-G1) is a point where cellular transformation can occur -During this time, cells pass through a transition phase known as a restriction point -Extracellular growth factors trigger reentry into G1, and GF are required to send the cells past the restriction point, or the point of no return G0 Phase (resting phase) - CORRECT ANSWER ✔✔✔ -After mitosis, cells may enter back into the G1 phase or go into a resting phase, known as G -Most cells in the human body reside in G -Exceptions to this are those that are (Resting in G0 phase) - CORRECT ANSWER ✔✔✔ -Exceptions to this are those that are metabollically active, such as -granulocytes
-An example of an inhibitory protein is p53 (AKA TP53) DNA Damage Checkpoints - CORRECT ANSWER ✔✔✔ -If DNA damage is present, cells are programmed to stop dividing or undergo apoptosis (programmed cell death) -The retinoblastoma protein (Rb), p53, and p21 are some of the most well- understood inhibitory proteins (IP) Inhibitory proteins p53 - CORRECT ANSWER ✔✔✔ -Levels of this IP regulate several important target genes -Will increase when DNA damage is present -Protects against inappropriate signal proliferation -sometimes called the "suicide gene" M Phase Checkpoints - CORRECT ANSWER ✔✔✔ When the cells prepare to divide, the chromosomes line up in the mitotic spindle. If the chromosomes are not properly aligned, division is not allowed to continue Immunity - CORRECT ANSWER ✔✔✔ Cells of the Immune System - CORRECT ANSWER ✔✔✔ Pluripotent Stem Cell - CORRECT ANSWER ✔✔✔ -The cells of the immune system are created in the bome marrow from what is know as a ___ -A stem cell that can differentiate into any cell type except for extraembryotic tissue, does not yet have a function Myeolid Precursor Cells - CORRECT ANSWER ✔✔✔ Mature into: -RBCS -Plts -WBCs (Granulocytes) Lymphoid Precursor Cells - CORRECT ANSWER ✔✔✔ Mature into: -Specialized WBCs called lymphocytes (Agranulocytes)
Lines of Defense: The Immune System's Response to Attack - CORRECT ANSWER ✔✔✔ Consists of 2 types of immunity: 1: Innate 2: Adaptive Innate Immunity - CORRECT ANSWER ✔✔✔ -First line of defense against a pathogen -Does not retain memory of the entity -Involves the following: (skin, mucous membranes, and normal flora of the skin and gut) (Cellular components such as phagocytes, natural killer cells, granulocytes, and macrophages)
- Phagocytes
- Natural Killer Cells
- Granulocytes
- Macrophages - CORRECT ANSWER ✔✔✔ 1.Cells that engulf and destroy invader
- Cells that sense receptors on self and non-self to determine if they should kill or not
- Type of WBC that have granules (Neutrophils Eosinophils - parasites Basophils - release histamine to stimulate immune response)
- Large phagocytic cells stimulated by infection Adaptive Immunity - CORRECT ANSWER ✔✔✔ -Stimulated if innate immunity is insufficient -leads to immune system memory
Helper T-Cells (CD4+) - CORRECT ANSWER ✔✔✔ -help other T-Cells by secreting chemicals -Help B Cells to respond -rapidly divide, in an effort to stay ahead of the antigen dividsion -some will turn into effector cells, which secrete different kinds of cytokines -respond similarly to B-Cells Cytotoxic T-Cells (CD8+) - CORRECT ANSWER ✔✔✔ -Directly kill cells for which they are activated to kill -rapidly divide, become mature cells, and start killing antigens Cytokines - CORRECT ANSWER ✔✔✔ -Secreted by lymphocytes -Tasked with eliminating the antigen -Multifunctional subsances having proinflammatory, anti-inflammatory, and regulatory functions in the immune system Cytokines Include.. - CORRECT ANSWER ✔✔✔ -Interferons (IFNs) -Tumor necrosis factors -Transforming GFs -Interleukins (IL -1, -2, -3, -4, -6, -8, -10, and -15) -These cytokines regulate antibody production and the functions of B and T cells as well as interact with antigen-presenting cells and NKCs
Benign Tumors - CORRECT ANSWER ✔✔✔ -encapsulated and grow in an orderly manner with smooth edges -Do not invade neighboring tissue -DO not metastasize to distant sites -the cells well differentiated in that they look like the parent cell Characteristics of Cancer Cells - CORRECT ANSWER ✔✔✔ -Malignant tumors are not encapsulated -Cell structure is different from parent tissue (no as well differentiated) -Cell division is uncontrolled -Cells are loosely adherent without contact inhibition -Cells are able to invade neighboring tissue -Cells can migrate and metastasize to distant sites -Can stimulate the development of new blood vessels to supply the tumor (angiogenesis) Proto-oncogene - CORRECT ANSWER ✔✔✔ -regulate normal cell growth and division -large family of genes that code for proteins and enzymes that turn on the cell cyle Oncogene - CORRECT ANSWER ✔✔✔ when mistakes in copies of DNA can occur, if a mutation occurs next to a proto-oncogene, it can "turn on" and become a ______ Examples of oncogoenes - CORRECT ANSWER ✔✔✔ 1. EGFR or Erb-B1 (codes for an epidermal GF receptor in the receptor-tyrosine kinase family ad is associated with head and neck and colorectal cancers)
Dimerization - CORRECT ANSWER ✔✔✔ 1. Homodimerization: binding with the same type of receptor, such as an epidermal GF receptor (EGFR) 1 receptor with another EGFR
- Heterodimerization: binding with a different kind of receptor, such as EGFR binding with EGFR Protein tyrosine kinases phosphorylates - CORRECT ANSWER ✔✔✔ -turned on by giving up a phosphate molecule -the message is now send via a "bucket bridage", or passing the message from one molecule to other signaling molecules until the message gets first into the cell nucleus -where it is transcribed Pathways - CORRECT ANSWER ✔✔✔ many pathways and crossalks signaling btw and among the different pathways, and they all have the power to control cell behavior in one way or another mitogen-activating protein kinase (Raf-1/MAPK) pathway - CORRECT ANSWER ✔✔✔ -shown to decrease the benefits of some cancer drugs -decrease disease-free survival time in some pts mammalian target of rapamycin (mTOR) survival pathway - CORRECT ANSWER ✔✔✔ -play a role in resistance to some chemotherapy agents in certain pts by keeping cells that have been exposed to chemotherapy from undergoing apoptosis -role in angiogenesis phosphoinositide 3-kinases (PI3K) - CORRECT ANSWER ✔✔✔ -transduction enzymes that activate Akt, leading to cell survival, increased cell proliferation, and growith Neoadjuvant Treatment - CORRECT ANSWER ✔✔✔ -treatment given as a first step to shrink a tumor before the main treatment, usually surgery -examples: chemo, radiation therapy, hormone therapy Adjuvant therapy - CORRECT ANSWER ✔✔✔ -additonal cancer treatment given after the primary treatment to lower the risk that the cancer can recur
-Examples: chemo, radiation therapy, hormone therapy, targeted therapy, or biologic therapy Dose density - CORRECT ANSWER ✔✔✔ -refers to the drug dose per unit of time -reduction of time between treatments to achieve higher concentration than in a standard treatment plan Dose intensity - CORRECT ANSWER ✔✔✔ -amount of drug delivered over time -smaller doses of chemotherapy given more frequently Relative dose intensity (RDI) - CORRECT ANSWER ✔✔✔ -calculated by comparing the dose that the pt received to the planned dose of the standard regimen Oral Chemotherapy - CORRECT ANSWER ✔✔✔ -greater challenge to adherence because the responsibility falls on the pt and caregiver Nonadherence - CORRECT ANSWER ✔✔✔ -pt takes too few or too many pills Overadherence - CORRECT ANSWER ✔✔✔ -when a pt believes a dose was missed or that "more is better", too much medication may be taken, leading to increased toxicity Factor affecting adherence - CORRECT ANSWER ✔✔✔ -provider relationship -side effects -necessity -routinization -support -lifestyle fit -cost -medication knowledge -pill burden -regiment complexity Lesson 2: Alkylating Agents - CORRECT ANSWER ✔✔✔ Alkylating Agents - CORRECT ANSWER ✔✔✔ -function by causing a break in the DNA helix strand, causing interference with DNA replication, which results in cell death
-nephrotoxic (IV hydration 2-3 L per day) -severe N/V -ovarian and testicular Cyclophosphamide (Cytoxin) - CORRECT ANSWER ✔✔✔ -Alkylating agent) -hemorrhagic cystitis (dysuria, hematuria, hemorrhage) -DC treatment if hemorrhagic cystitis -adequate hydration Oxaliplatin - CORRECT ANSWER ✔✔✔ -Alkylating agent -irritant and vesicant, extra caution with the IV site -peripheral neuropathy is a dose-limiting side effect (exacerbated by cold temperatures) -avoid cold drinks and foods, wearing gloves and warm shoes -avoid breathing cold air Intrathecal Chemotherapy - CORRECT ANSWER ✔✔✔ -injects chemo directly into the subarachnoid space so it reaches the CNS -Often used to treat leukemia and lymphoma that has spread to the CNS since most IV chemo does not cross the blood-brain barrier -only MTX and cytarabine via this route -IT hydrocortisone is often given at the same time to reduce inflammation
-MUST be preservative free to avoid CNS irritation Chemotherapy-Induced N/V (CINV) Risk factors - CORRECT ANSWER ✔✔✔ -younger -have a hx of low or no alcohol consumption -are female -hx of morning sickness -prone to motion sickness -have had chemo previously Types of CINV - CORRECT ANSWER ✔✔✔ -Acute: occurring within 24 hours -Delayed: from 24 hour - 5 days after -Breakthrough: Occurring despite treatment -Anticipatory: triggered by taste, odor, memories, visions, anxiety r/t chemo -Refractory: occurring despite subsequent cycles when treatment failed in earlier cycles Prevention/Treatment of hand foot syndrome - CORRECT ANSWER ✔✔✔ -limit exposure of hands and feet to hot water -take cool showers -avoid exposure to sources of heat, such as using saunas or sitting in the sun -avoid activities that cause unnecessary force or friction on the hands or feet, such as running or aerobics -avoid contact with harsh chemicals used in detergents and household cleaning products -avoid activities that require you to press your hand against a hard surface
Stomatitis - CORRECT ANSWER ✔✔✔ -specifically inflammatory conditions of the mouth Xerostomia - CORRECT ANSWER ✔✔✔ -dryness of the mouth caused by damage to or dysfunction of the salivary glands Hypersensitivity Reaction (HSR) - CORRECT ANSWER ✔✔✔ -body mounts an immunologic response to a foreign substance or antigen, resulting in local tissue injury IgE-mediated - CORRECT ANSWER ✔✔✔ -immediate (within 5 minute) HSR, present like classic allergic reactions T-Cell--Mediated - CORRECT ANSWER ✔✔✔ -Delayed hypersensitivity reactions, can occur any time after the immediate hypersensitivity window, even days or weeks Type 1 HSR early S/SX - CORRECT ANSWER ✔✔✔ -pruritus -restlessness, agitation, anxiety, feeling of impending doom -fever, flushing, chills -urticaria (hives) -maculopapular rash -edema of hands, face, and feet -N/V -dyspnea, wheezing, bronchospasm -hypotension, cyanosis -circulatory and respiratory collapse Type IV HSR - CORRECT ANSWER ✔✔✔ -pneumonitis -mucositis -contact dermatitis -granulomas -Graph vs host disease Lesson 7: Cumulative Dose - CORRECT ANSWER ✔✔✔ Cumulative dose - CORRECT ANSWER ✔✔✔ total amount of one antineoplastic agent given to the pt, adding up each time that the pt has received it Cumulative lifetime dose - CORRECT ANSWER ✔✔✔ -"cumulative dose should not exceed..."
-total amount of specific antineoplastic agents that can be safely given over the course of a pt's lifetime Extravasation - CORRECT ANSWER ✔✔✔ -leak of a drug capable of causing tissue damage from the vessel in which it is being administered into the surround tissue Irritant - CORRECT ANSWER ✔✔✔ -causes inflammation, pain, and burning but rarely causes tissue necrosis Vesicants - CORRECT ANSWER ✔✔✔ -causes blistering and significant pain and tissue damage and destruction, leading to tissue death Vesicants in PIVs - CORRECT ANSWER ✔✔✔ -Do not use IV in hand, wrist, AC areas -Do NOT place the IV below a recent ventipuncture site used (<24 hours) -Use a flexible IV catheter When a vesicant extravasation occurs or is suspected, take the following steps: - CORRECT ANSWER ✔✔✔ 1. Immediately STOP administering the vesicant and IV fluids
- Disconnect the IV tubing from the IV device. Do not remove the IV device or noncoring port needle
- Attempt to aspirate residual vesicant from the IV device or port needling use a small (1-3 mL) syringe
- Remove the peripheral IV device or port needle
- Initiate appropriate management measures Managing Non-DNA Binding Vesicant Extravasation - CORRECT ANSWER ✔✔✔ - Vinca Alkaloids (vincristine, vinblastine) -Do not bind to DNA in healthy cells when they extravasate into tissue. Indirect effect on healthy tissue -Treat with heat, elevation, and hyaluronidase local injection (spreads the vesicant through the tissue for faster metabolism of the vesicant agent)
-controlling or stabilizing disease -maintaining or enhancing quality of life -decreasing the severity of toxicities from other therapies Receptor - CORRECT ANSWER ✔✔✔ -molecule inside or on the surface of a cell that binds to a specific substance causes a specific effect in that cell Monomer - CORRECT ANSWER ✔✔✔ molecule that can join with other identical monomers to form a structure called a polymer Ligand - CORRECT ANSWER ✔✔✔ a substance that forms a complex with another biomolecule to exert a biologic effect Ligand Binding - CORRECT ANSWER ✔✔✔ process by which the ligand attaches to a specific receptor site and activates that receptor, activating the signaling pathway Dimerization - CORRECT ANSWER ✔✔✔ 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 - CORRECT ANSWER ✔✔✔ 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 - CORRECT ANSWER ✔✔✔ activation of a chemical process to initiate signaling targeted therapies work by doing the following - CORRECT ANSWER ✔✔✔ 1. blocking angiogenesis
- blocking signals inside or outside the cell
- delivering toxic substances to the cell
- stimulating the body's immune system BCR/ABL - CORRECT ANSWER ✔✔✔ -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 - CORRECT ANSWER ✔✔✔ this is the primary angiogenic factor produced by cells mTOR - CORRECT ANSWER ✔✔✔ -target of rapamycin -a protein that tells cells when to grow, divide, and survive Two ways that angiogenesis inhibitors work - CORRECT ANSWER ✔✔✔ 1. some intergere with action of VEGF which stimulates n ew blood vessel formation
- others target their molecules that stimulate new blood vessel growth Small Molecule Compound Targeted Therapies - CORRECT ANSWER ✔✔✔ -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 - CORRECT ANSWER ✔✔✔ - 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 Lesson 12: Immunotherapy - CORRECT ANSWER ✔✔✔ Immunotherapy works by - CORRECT ANSWER ✔✔✔ -stopping or slowing the growth of cancer cells
