Signaling Pathways and Apoptosis Mechanisms
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Questions and Answers

Which molecule is activated by PIP3 in the Pisk pathway?

  • Raf
  • Erk
  • Akt (PKB) (correct)
  • MEK
  • Mutated Ras can complicate treatment options for cancer patients.

    True (A)

    Name one drug that works on the Pisk pathway.

    Idelalisib

    The protein ___ is activated by the Apoptosome to initiate controlled cell death.

    <p>caspase-9</p> Signup and view all the answers

    Match the following terms with their corresponding pathways:

    <p>EGFR = Pisk Pathway Ras = Ras Pathway BAX = Intrinsic Pathway Death ligands = Extrinsic Pathway</p> Signup and view all the answers

    What is the main role of Akt in the Pisk pathway?

    <p>Inhibits apoptosis (C)</p> Signup and view all the answers

    The extrinsic pathway of apoptosis is initiated by internal stimuli.

    <p>False (B)</p> Signup and view all the answers

    What leads to the activation of caspase-3 and caspase-7 in the intrinsic pathway?

    <p>Activation of caspase-9</p> Signup and view all the answers

    What is the role of activated caspase-8 in the apoptosis process?

    <p>Directly activates executioner caspases (C)</p> Signup and view all the answers

    Caspase-3 is responsible for initiating the apoptotic process.

    <p>False (B)</p> Signup and view all the answers

    What type of therapy involves modifying a patient's T-cells to attack cancer cells?

    <p>CAR T-cell Therapy</p> Signup and view all the answers

    The binding of PD-L1 on tumor cells sends a __________ signal to T-cells, preventing them from attacking the tumor.

    <p>stop</p> Signup and view all the answers

    Match the immunotherapy types with their descriptions:

    <p>Checkpoint Inhibitors = Drugs that block proteins allowing T-cells to kill cancer cells CAR T-cell Therapy = Modifies T-cells to target specific cancer cells Cancer Vaccines = Stimulates the immune system to attack cancer PD-1/PD-L1 Inhibitors = Prevents cancer cells from turning off T-cells</p> Signup and view all the answers

    Which of the following is NOT a side effect of immunotherapy?

    <p>Increased appetite (A)</p> Signup and view all the answers

    Immunotherapy can only target solid tumors, not blood cancers.

    <p>False (B)</p> Signup and view all the answers

    What are the two main checkpoint proteins inhibited by therapeutic drugs in immunotherapy?

    <p>CTLA-4 and PD-1</p> Signup and view all the answers

    What is the primary function of the PD-1 receptor when it binds to PD-L1?

    <p>To reduce T-cell activity (B)</p> Signup and view all the answers

    Monoclonal antibodies can enhance the body's ability to destroy normal cells.

    <p>False (B)</p> Signup and view all the answers

    What is the main advantage of using bispecific antibodies in cancer treatment?

    <p>They can simultaneously target two different antigens or sites, enhancing the immune response against tumors.</p> Signup and view all the answers

    PD-1 receptor interaction with PD-L1 helps prevent __________________ by regulating T-cell activity.

    <p>autoimmunity</p> Signup and view all the answers

    Which of the following describes how monoclonal antibodies work?

    <p>They attract immune cells to targeted cancer cells. (A)</p> Signup and view all the answers

    Epigenetic changes do not alter the DNA sequence but can still affect gene expression.

    <p>True (A)</p> Signup and view all the answers

    Match the following types of antibodies with their characteristics:

    <p>Monoclonal Antibodies = Lab-produced to target specific antigens Bispecific Antibodies = Can bind to two different antigens simultaneously Trastuzumab = Targets HER-2 positive breast cancer Epigenetics = Heritable gene expression modifications without DNA sequence changes</p> Signup and view all the answers

    DNA methylation is a process in which __________ groups are added to DNA, often leading to gene silencing.

    <p>methyl</p> Signup and view all the answers

    Study Notes

    Signaling Pathways

    • PI3K Pathway: Initiated when a growth factor binds to a tyrosine kinase receptor (RTK) on the cell surface. This triggers a cascade of events involving PI3K, PIP2, PIP3, Akt, BAD, mTOR, GSK-3B, and Foxo, leading to cell growth, proliferation, and survival.
    • Drugs that target PI3K pathway: Idelalisib, Copanlisib, Duvelisib
    • Ras Pathway: Activated when a growth factor binds to an RTK on the cell surface, causing receptor dimerization and autophosphorylation. The active Ras protein activates Raf, MEK, and ERK, ultimately leading to gene transcription for cell cycle progression, differentiation, survival, and growth.
    • Drugs that target Raf pathway: Vemurafenib, Trametinib, Dabrafenib, Sorafenib
    • Mutations in Ras and Raf are common in cancers: These mutations can lead to uncontrolled cell proliferation.
    • Mutated Ras: Makes cancer cells resistant to drugs targeting this pathway.

    Apoptosis

    • Intrinsic Pathway: Triggered by internal stimuli signaling unfavorable conditions for survival. Pro-apoptotic members of the Bcl-2 family (BAX and BAK) activate, leading to mitochondrial permeabilization and release of cytochrome c and apoptotic factors into the cytoplasm. Cytochrome c and Apaf-1 form the apoptosome, which activates caspase-9, leading to caspase cascade activation and controlled cell death.
    • Extrinsic Pathway: Induced by extracellular death ligands binding to death receptors on the cell surface. This triggers receptor trimerization, assembly of the DISC complex, and activation of caspase-8, which activates caspase-3 and leads to apoptosis.

    Immunotherapy

    • Checkpoint Inhibitors: Block checkpoint proteins on T-cells, allowing immune cells to recognize and kill cancer cells.
      • CTLA-4 inhibitors: Block CTLA-4 on T-cells, enhancing their activity. Example: Ipilimumab.
      • PD-1/PD-L1 inhibitors: Block PD-1/PD-L1 pathway interaction, preventing cancer cells from inactivating T-cells. Examples: Pembrolizumab, Nivolumab.
    • CAR T-cell Therapy: Patients' T-cells are engineered to target specific proteins on cancer cells, enhancing their anti-cancer activity. Often used for blood cancers like leukemia and lymphoma.
    • Cancer Vaccines: Stimulate the immune system to attack cancer cells. Examples include HPV vaccines, which prevent cancer related to certain viral infections.

    Mechanism of Action of Immunotherapy

    • Enhancement of T-cell activity by blocking "off switches" on T-cells (PD-1/PD-L1, CTLA-4).
    • Providing specific tools to fight certain cancers by engineering T-cells to target cancer cells (CAR T-cell therapy).
    • Stimulating the immune system to fight cancer cells (cancer vaccines).

    Side Effects of Immunotherapy

    • Autoimmune disease, fatigue, fever, flu-like symptoms, and organ inflammation.

    PD-1/PD-L1 Pathway

    • In cancer: PD-L1 binding to PD-1 on T-cells inhibits their activity, allowing cancer cells to evade immune detection and destruction.
    • Under normal conditions: PD-1/PD-L1 interaction helps regulate T-cell activity, preventing autoimmunity.
    • Monoclonal antibodies: Disrupt PD-1/PD-L1 interaction, reactivating T-cells to recognize and destroy cancer cells.

    Monoclonal Antibodies (mAbs)

    • How they work: Target specific antigens on cancer cells, attracting immune cells to kill cancer cells, blocking signals promoting cancer cell growth, and delivering treatments directly to cancer cells.
    • Advantages: Targeted treatment, fewer side effects, compatible with other treatments.

    Bispecific Antibodies

    • How they work: Bind simultaneously to two different antigens, targeting tumor cells and immune cells, and stimulating immune response against cancer cells. Some bispecific antibodies block signaling pathways that promote cancer growth.
    • Advantages: Dual-targeting, increased effectiveness, greater control over immune response.

    Epigenetics

    • Epigenetic changes: Modifications in gene expression without altering the DNA sequence.
    • Main mechanisms: DNA methylation, histone modifications, and non-coding RNAs.
    • DNA methylation: Addition of methyl groups to DNA, often silencing genes.

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    Related Documents

    Pathways & Apoptosis PDF

    Description

    Explore the intricate details of signaling pathways including the PI3K and Ras pathways, as well as the mechanisms of apoptosis. This quiz covers key concepts, associated drugs, and the impact of mutations in cancer biology. Test your understanding of how these pathways influence cell growth and survival.

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