Questions and Answers
What is the primary mechanism of action of platinum-based chemotherapy in lung cancer treatment?
What is the primary reason for the development of cisplatin resistance in lung cancer treatment?
What is the main adverse effect of oxaliplatin that is more pronounced than with cisplatin?
What is the primary function of the major histocompatibility complex (MHC) in immunology?
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What is the main mechanism by which cancer cells evade the immune system?
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What is the primary adverse effect of immune checkpoint inhibitors (ICIs)?
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What is the primary mechanism of action of nivolumab in the 'Checkmate 816' trial?
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What is the primary difference between neoadjuvant and adjuvant therapy?
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What is the primary mechanism of action of 5-HT3 receptor antagonists in managing severe nausea and vomiting?
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What is the primary reason for the approval of immune checkpoint inhibitors as the standard of care in modern oncology?
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What is the primary mechanism of action of PD-1/PD-L1 inhibitors in cancer treatment?
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Which of the following is NOT a tyrosine kinase inhibitor?
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What is the primary target of EGFR tyrosine kinase inhibitors?
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Which of the following is a contraindication for the use of tyrosine kinase inhibitors?
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What is the response rate of ALK tyrosine kinase inhibitors in patients with ALK gene mutations?
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What is the role of primary care, urgent care, EM, and IM PAs in cancer treatment decision-making?
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What is the mechanism of action of CTLA-4 inhibitors in cancer treatment?
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Which of the following is a characteristic of tyrosine kinase inhibitors?
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Study Notes
What is Cancer?
- Cancer is when cells grow uncontrollably due to genetic alterations.
- These alterations affect genes, which are the instruction manual for cell behavior.
- Cancerous cells can invade or damage nearby tissues or travel to other locations.
Treatment Strategies
- Neoadjuvant therapy: giving drugs before surgery or radiation.
- Adjuvant therapy: giving drugs after surgery or radiation.
- Combination therapies can include chemotherapy, checkpoint inhibitors, and targeted therapies.
Traditional Treatment of Lung Cancer
- Platinum-based chemotherapy: Cisplatin, Carboplatin, and Oxaliplatin.
- Platinum moieties bind to DNA, interfering with synthesis, leading to cellular apoptosis.
Cisplatin Resistance
- Decreasing drug uptake
- Increasing drug efflux
- Inducing drug detoxification
- DNA repair mechanisms
Adverse Effects of Lung Cancer Treatment
- Severe N/V: managed with 5-HT3 receptor antagonists (like ondansetron)
- Nephrotoxic: more important with cisplatin, mitigated by aggressive IV hydration
- Myelosuppression: more important with carboplatin and oxaliplatin
- Neurotoxic: cold-induced and cumulative neuropathy with oxaliplatin
- Ototoxic, hypomagnesemia, hypocalcemia, and hypokalemia
Immunology Refresher
- MHC on antigen-presenting cells (APCs) presents antigens to T-cell receptor (TCR)
- 2nd signal often required for T-cell activation, like CD80 from APC to CD28 on T-cell
- Activated T-cells bring CTLA-4 and PD-1 to their surface to prevent excessive inflammation
How Cancer Subverts Immunology
- Cancer cells can bind to inhibitory receptors on T-cells and deactivate them
- Immune checkpoint inhibitors (ICIs) target these receptors to prevent deactivation
Immune Checkpoint Inhibitors
- 2011: first approval for ICIs
- Over 80 FDA-approved uses for over 17 concerns
- Considered the standard of care in modern oncology
- AE: autoimmune response to normal tissues, treated with corticosteroids
PD-1/PD-L1 Inhibitors
- Nivolumab (Opdivo), PD-1
- Pembrolizumab (Keytruda), PD-1
- Cemiplimab (Libtayo), PD-1
- Atezolizumab (Tecentriq), PD-L1
- Durvalumab (Imfinzi), PD-L1
CTLA-4 Inhibitors
- Ipilimumab (Yervoy)
- Tremelimumab (Imjudo)
Tyrosine Kinase Inhibitors
- Gene mutations cause abnormal cell behaviors
- Tyrosine kinases are involved in cell growth processes
- Each has their own adverse effects, monitoring parameters, and contraindications
ALK Tyrosine Kinase Inhibitors
- ALK gene codes for anaplastic lymphoma kinase (ALK), involved in cell growth
- Mutated forms of ALK gene and protein found in non-small cell lung cancer
- ALK TKIs recommended as first-line therapy in patients with ALK gene mutations, with response rates between 47-83%
EGFR Tyrosine Kinase Inhibitors
- EGF-R gene codes for Epidermal Growth Factor (EGF) Receptor on cell surface
- Mutations in the gene can cause EGF-R upregulation on cancer cells
- EGFR TKIs recommended as first-line therapy in patients with EGFR gene mutations, with response rates of at least 70%
Final Thoughts
- Decisions on cancer treatments are ultimately not up to primary care, urgent care, EM, or IM PAs
- Recognize these drugs and their potential adverse effects, which can be acute symptoms seen in patients
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Description
A quiz on lung malignancy treatment, covering clinical pharmacology concepts, taught by Michael A. Sharma from UT Southwestern Medical Center and Franklin Pierce University.
