Cancer Flashcards
Describe the process of whole-exome sequencing (WES) and its role in cancer research.
WES involves sequencing the protein-coding regions (exons) of the genome. This allows researchers to identify somatic mutations specific to tumor cells, providing insights into the genetic drivers of cancer development and potential therapeutic targets.
Explain the concept of phylogenetic signal in the context of tumor evolution.
Phylogenetic signal refers to the tendency of closely related tumor cells to share similar phenotypic or genotypic characteristics. Analyzing phylogenetic signal in gene expression patterns can reveal genes and pathways under selection pressure during tumor evolution.
What are eQTLs, and how can they be used to understand the genetic control of gene expression in cancer?
eQTLs (expression quantitative trait loci) are genetic variants associated with variations in gene expression levels. Studying eQTLs in tumors can help identify genetic factors influencing gene expression, potentially explaining differential drug responses and revealing new therapeutic targets.
Define the dN/dS ratio and its significance in identifying genes under selection pressure in cancer.
The dN/dS ratio compares the rate of non-synonymous (amino acid-changing) to synonymous (silent) mutations in a gene. A high dN/dS ratio suggests positive selection, indicating the gene is undergoing adaptive evolution, potentially driving tumor growth.
Explain the concept of subclonal selection and its implications for cancer treatment.
Subclonal selection occurs when specific subpopulations of tumor cells, harboring advantageous mutations, are preferentially selected for during tumor growth and treatment. This leads to tumor heterogeneity and potential resistance to therapy.
What is the mechanism of action of PD-1 inhibitors in cancer immunotherapy?
PD-1 inhibitors block the interaction between PD-1 receptors on T cells and PD-L1 ligands on tumor cells. This releases the inhibitory signal, enabling T cells to recognize and attack tumor cells more effectively.
Describe the challenges associated with identifying effective drug combinations in cancer treatment.
Identifying effective drug combinations is challenging due to complex interactions between drugs and tumor cells. Factors like
- drug resistance,
- tumor heterogeneity, and
- potential synergistic or antagonistic effects
need careful consideration.
How can CRISPR-Cas9 technology be utilized for developing personalized T cell therapies?
CRISPR-Cas9 can be used to modify T cells, enabling the introduction of specific TCRs or CARs targeting tumor-specific antigens. This allows for the development of personalized T cell therapies with enhanced tumor recognition and killing capabilities.
Explain the concept of “exhaustion” in CAR T cells and its impact on treatment efficacy.
CAR T cell exhaustion refers to the gradual loss of function and proliferative capacity in engineered T cells due to chronic antigen stimulation. This can limit the long-term efficacy of CAR T cell therapies.
Discuss the role of high-throughput screening in identifying potential drug candidates.
High-throughput screening involves testing vast libraries of compounds against specific targets or cellular pathways. This accelerates the identification of potential drug candidates with desired biological activity.
What are some examples of drugs derived from natural sources?
Digitalis:This drug originates from the foxglove plant and is used to treat heart conditions like arrhythmias. The active ingredient responsible for its therapeutic effects is called digitalin.
Taxol (Paclitaxel): Isolated from the bark of the Pacific yew tree, taxol acts as a microtubule stabilizing agent, preventing cell division. This property makes it valuable as an anti-cancer therapy, particularly for breast and ovarian cancers.
What is the Drug Project Operating Model in pharmaceutical research?
A systematic approach adopted by pharmaceutical companies to guide drug discovery and development. It often consists of a series of linear steps:
Target Identification: This initial phase focuses on pinpointing a specific biological target, often a protein, that plays a key role in the disease process.
Molecule Identification: Researchers employ techniques like structure-based drug design or high-throughput screening to discover molecules that effectively interact with the chosen target.
Lead Optimization: The identified molecules undergo refinement and modification to enhance their potency, selectivity, and safety.
Preclinical Studies: Before human testing, extensive laboratory and animal studies are conducted to evaluate the drug’s efficacy, safety, and pharmacokinetic properties.
Clinical Trials:Human clinical trials are meticulously designed to assess the drug’s safety, efficacy, and optimal dosage in patients.
Regulatory Approval: If clinical trials demonstrate the drug’s safety and effectiveness, the pharmaceutical company seeks approval from regulatory agencies (e.g., FDA in the US) to market the drug.
How is artificial intelligence (AI) used in drug discovery?
Target Identification: AI algorithms analyze vast datasets to identify potential drug targets and predict their relevance to specific diseases.
Virtual Screening: AI helps researchers rapidly screen millions of virtual compounds to find those likely to bind to the target.
Lead Optimization: AI guides the optimization process by predicting the properties and activity of modified molecules.
Drug Repurposing:AI algorithms identify existing drugs that could be repurposed for new therapeutic applications.
What is an angiogenesis inhibitor and how is it evaluated?
A drug that blocks the formation of new blood vessels (angiogenesis-crucial for tumor growth and spread)
For evaluation: use advanced imaging techniques to observe the drug’s impact on:
- Tip Formation:The formation of specialized cells at the leading edge of new blood vessels.
- Sprouting: The emergence of new blood vessels from existing ones.
These imaging techniques help distinguish between true angiogenesis inhibitors and vascular disrupting agents (which simply damage existing blood vessels).
What is apoptosis and how is it relevant in cancer drug research?
Cell death (tightly controlled), in cancer apoptosis is key measure of a drugs effectiveness
- Caspases: Apoptosis is executed by a family of enzymes called caspases. When activated, these enzymes dismantle cellular components, leading to cell death.
Apoptosis Assays: Scientists employ various laboratory techniques to measure caspase activity and other hallmarks of apoptosis to determine if a drug is successfully inducing cancer cell death.
