Podcast
Questions and Answers
What refinement has optimized the effectiveness of chemotherapy, specifically related to a patient's genetic makeup?
What refinement has optimized the effectiveness of chemotherapy, specifically related to a patient's genetic makeup?
- Increasing the dosage of chemotherapeutic agents to overcome resistance.
- Administering chemotherapy only during specific phases of the cell cycle.
- Tailoring the treatment to the genetics of the patient and their cancer. (correct)
- Using only non-cell cycle specific (NCCS) drugs, ensuring broad action.
In the context of cancer development, what distinguishes a tumor initiator from a tumor promoter?
In the context of cancer development, what distinguishes a tumor initiator from a tumor promoter?
- Tumor initiators enhance immune response, while tumor promoters suppress it.
- Tumor initiators directly activate oncogenes, while tumor promoters inactivate tumor suppressor genes.
- Tumor initiators are mutagens that cause genetic changes, while tumor promoters induce proliferation. (correct)
- Tumor initiators induce cell proliferation, whereas tumor promoters cause direct DNA damage.
If resistance to a chemotherapy drug develops because cancer cells upregulate the expression of specific enzyme targets, which therapeutic strategy might be most effective in overcoming this resistance?
If resistance to a chemotherapy drug develops because cancer cells upregulate the expression of specific enzyme targets, which therapeutic strategy might be most effective in overcoming this resistance?
- Switching to a chemotherapy drug that targets a completely different cellular process to bypass the overexpressed enzyme.
- Using an adjuvant therapy that specifically inhibits the overexpressed enzyme, thereby restoring the drug's effectiveness. (correct)
- Administering the chemotherapy drug in shorter, more frequent intervals to maintain a consistently high concentration.
- Increasing the dosage of the current chemotherapy drug to overwhelm the increased enzyme activity.
In the context of tumor suppressor genes, what is the functional consequence of a mutation leading to a 'mutator phenotype'?
In the context of tumor suppressor genes, what is the functional consequence of a mutation leading to a 'mutator phenotype'?
How does the development of aneuploidy contribute to cancer progression?
How does the development of aneuploidy contribute to cancer progression?
How does the mechanism of action of alkylating agents, a class of genotoxic chemotherapeutics, lead to cancer cell death?
How does the mechanism of action of alkylating agents, a class of genotoxic chemotherapeutics, lead to cancer cell death?
How does understanding the fractional kill hypothesis influence the scheduling and dosing of chemotherapy treatments?
How does understanding the fractional kill hypothesis influence the scheduling and dosing of chemotherapy treatments?
What is a critical difference between cell cycle-specific (CCS) and non-cell cycle-specific (NCCS) chemotherapy drugs?
What is a critical difference between cell cycle-specific (CCS) and non-cell cycle-specific (NCCS) chemotherapy drugs?
What is the key function of topoiosomerase I and II inhibitors in cancer chemotherapy, and during which phase of the cell cycle are they most effective?
What is the key function of topoiosomerase I and II inhibitors in cancer chemotherapy, and during which phase of the cell cycle are they most effective?
What is implied by the statement: 'Cancer is primarily a disease of old age'?
What is implied by the statement: 'Cancer is primarily a disease of old age'?
What is a main consideration when administering genotoxic agents?
What is a main consideration when administering genotoxic agents?
What aspect of the cell cycle is specifically targeted by chemotherapeutic drugs classified as 'mitotic spindle poisons'?
What aspect of the cell cycle is specifically targeted by chemotherapeutic drugs classified as 'mitotic spindle poisons'?
What strategy do tumors employ to evade the effects of chemotherapeutic drugs?
What strategy do tumors employ to evade the effects of chemotherapeutic drugs?
When tumors fail to response to the the effects of Tamoxifen, what could be the reason?
When tumors fail to response to the the effects of Tamoxifen, what could be the reason?
In which type of cancer is radiation recall reaction seen and what are the most common symptoms?
In which type of cancer is radiation recall reaction seen and what are the most common symptoms?
In the context of precision medicine, how do targeted therapies like Imatinib (Gleevec) work?
In the context of precision medicine, how do targeted therapies like Imatinib (Gleevec) work?
If a chemotherapeutic agent is described as a 'P-glycoprotein inhibitor', what implication would this have for cancer treatment strategy?
If a chemotherapeutic agent is described as a 'P-glycoprotein inhibitor', what implication would this have for cancer treatment strategy?
What are some key components of an antibody-drug conjugate?
What are some key components of an antibody-drug conjugate?
If cancer cells evade apoptosis, what are some contributing factors?
If cancer cells evade apoptosis, what are some contributing factors?
What is a key fact about combination therapy?
What is a key fact about combination therapy?
A researcher is investigating a new drug that targets specific cancer cells, but finds that the drug is effective in vitro but less successful in animals. After further testing, it is determined that specific enzymes are causing the drug to become less effective. Why might the presence of liver and kidney issues be relevant?
A researcher is investigating a new drug that targets specific cancer cells, but finds that the drug is effective in vitro but less successful in animals. After further testing, it is determined that specific enzymes are causing the drug to become less effective. Why might the presence of liver and kidney issues be relevant?
Which concept poses challenges when using cytotoxic agents, specifically because they cause DNA damage?
Which concept poses challenges when using cytotoxic agents, specifically because they cause DNA damage?
How does Herceptin work as a cancer treatment?
How does Herceptin work as a cancer treatment?
Most chemotherapeutic drugs have serious side effects related to normal and rapidly dividing cells. Which are the most commonly affected cells?
Most chemotherapeutic drugs have serious side effects related to normal and rapidly dividing cells. Which are the most commonly affected cells?
Which hallmark of cancer describes the ability of cancer cells to sustain their own proliferation without external stimuli?
Which hallmark of cancer describes the ability of cancer cells to sustain their own proliferation without external stimuli?
A researcher discovers a novel compound that selectively inhibits the function of thymidylate synthase. How would they classify this compound?
A researcher discovers a novel compound that selectively inhibits the function of thymidylate synthase. How would they classify this compound?
What is the significance of "CHK 1/2 inhibitors" in cancer treatment?
What is the significance of "CHK 1/2 inhibitors" in cancer treatment?
A new study shows that a genetic mutation is prevalent in families. What is a possible risk?
A new study shows that a genetic mutation is prevalent in families. What is a possible risk?
A diagnostic test assesses the microscopic grade of a tumor. What tumor property correlates with a higher grade histologically?
A diagnostic test assesses the microscopic grade of a tumor. What tumor property correlates with a higher grade histologically?
What therapeutic action is achieved by Aromatase Inhibitors?
What therapeutic action is achieved by Aromatase Inhibitors?
How is cancer treated with radio/chemotherapy?
How is cancer treated with radio/chemotherapy?
What must occur to treat cancer with combination therapy?
What must occur to treat cancer with combination therapy?
How are side effects managed?
How are side effects managed?
One factor of cancer is that cells go through a dysregulated cell cycle. The stages of the cell cycle are highly intricate and have features of their own, how can chemotherapeutics aid in controlling the dysregulated cell cycle?
One factor of cancer is that cells go through a dysregulated cell cycle. The stages of the cell cycle are highly intricate and have features of their own, how can chemotherapeutics aid in controlling the dysregulated cell cycle?
What steps are involved with cancer from hyperplasia through to metastasis?
What steps are involved with cancer from hyperplasia through to metastasis?
In which scenario would chemotherapy likely demonstrate the highest efficacy, considering tumor growth dynamics?
In which scenario would chemotherapy likely demonstrate the highest efficacy, considering tumor growth dynamics?
How do cytotoxic chemotherapeutic agents induce cell death in rapidly dividing cells?
How do cytotoxic chemotherapeutic agents induce cell death in rapidly dividing cells?
Which of the following strategies is least likely to be a guideline for drug selection in combination therapy?
Which of the following strategies is least likely to be a guideline for drug selection in combination therapy?
Which factor would most significantly compromise the effectiveness of a cell cycle-specific (CCS) drug?
Which factor would most significantly compromise the effectiveness of a cell cycle-specific (CCS) drug?
What is the most critical implication of the finding that a patient carries a MUT/MUT allele for TPMT before administering thiopurine drugs?
What is the most critical implication of the finding that a patient carries a MUT/MUT allele for TPMT before administering thiopurine drugs?
A patient with breast cancer is prescribed Tamoxifen, but the physician notes that the patient is also taking an antidepressant, what is the major concern?
A patient with breast cancer is prescribed Tamoxifen, but the physician notes that the patient is also taking an antidepressant, what is the major concern?
What cellular event is most directly inhibited by drugs classified as 'topoisomerase inhibitors'?
What cellular event is most directly inhibited by drugs classified as 'topoisomerase inhibitors'?
How do genotoxic chemotherapeutic agents typically initiate cell death?
How do genotoxic chemotherapeutic agents typically initiate cell death?
What is the primary mechanism by which methotrexate exerts its cytotoxic effect on cancer cells?
What is the primary mechanism by which methotrexate exerts its cytotoxic effect on cancer cells?
Which scenario best describes how cancer cells evade the effects of hormonal therapies like selective estrogen receptor modulators (SERMs)?
Which scenario best describes how cancer cells evade the effects of hormonal therapies like selective estrogen receptor modulators (SERMs)?
How does the inherent heterogeneity within tumors complicate the response to chemotherapy?
How does the inherent heterogeneity within tumors complicate the response to chemotherapy?
What is a critical function of tumor suppressor genes in maintaining genomic stability?
What is a critical function of tumor suppressor genes in maintaining genomic stability?
During which phase of the cell cycle do topoisomerase II inhibitors like etoposide exert their primary cytotoxic effects?
During which phase of the cell cycle do topoisomerase II inhibitors like etoposide exert their primary cytotoxic effects?
In which clinical setting would angiogenesis inhibitors be least effective?
In which clinical setting would angiogenesis inhibitors be least effective?
What mechanism underlies the capacity of cancer cells to sustain proliferative signaling, one of the recognized hallmarks of cancer?
What mechanism underlies the capacity of cancer cells to sustain proliferative signaling, one of the recognized hallmarks of cancer?
Why might a tumor with a mutation that causes upregulation of thymidylate synthase be resistant to 5-Fluorouracil?
Why might a tumor with a mutation that causes upregulation of thymidylate synthase be resistant to 5-Fluorouracil?
Which of the following represents a significant challenge in the design and application of chemotherapy regimens?
Which of the following represents a significant challenge in the design and application of chemotherapy regimens?
Why is scheduling is crucial for optimizing the efficacy of cell cycle-specific (CCS) drugs?
Why is scheduling is crucial for optimizing the efficacy of cell cycle-specific (CCS) drugs?
What is the role of leucovorin given during treatments using methotrexate?
What is the role of leucovorin given during treatments using methotrexate?
When compared to traditional chemotherapeutic agents, what is the key difference for molecularly targeted cancer therapies, such as tyrosine kinase inhibitors (TKIs)?
When compared to traditional chemotherapeutic agents, what is the key difference for molecularly targeted cancer therapies, such as tyrosine kinase inhibitors (TKIs)?
A researcher discovers a novel compound that effectively inhibits cancer cell proliferation in vitro. Initial in vivo studies show minimal effect. What is a likely reason?
A researcher discovers a novel compound that effectively inhibits cancer cell proliferation in vitro. Initial in vivo studies show minimal effect. What is a likely reason?
Which event in cancer initiation is best described tumor promoters?
Which event in cancer initiation is best described tumor promoters?
Why are cancers often treated using combination therapy?
Why are cancers often treated using combination therapy?
A patient is diagnoses with a high-grade tumor, how does this affect prognosis?
A patient is diagnoses with a high-grade tumor, how does this affect prognosis?
A patient is being treated with hormone therapy and is administered Aromatase Inhibitors; what will the expected result be?
A patient is being treated with hormone therapy and is administered Aromatase Inhibitors; what will the expected result be?
A researcher finds that a novel therapeutic agent effectively kills tumor cells in vitro but shows poor efficacy in vivo. What factor is responsible?
A researcher finds that a novel therapeutic agent effectively kills tumor cells in vitro but shows poor efficacy in vivo. What factor is responsible?
What are a few reasons why cancer is primarily a disease of old age?
What are a few reasons why cancer is primarily a disease of old age?
What makes HER2/neu a viable cancer treatment?
What makes HER2/neu a viable cancer treatment?
How are side effects like nausea and vomiting reduced for cancer patients?
How are side effects like nausea and vomiting reduced for cancer patients?
Consider a scenario in which a tumor has undergone clonal proliferations, what is the first thing that must occur?
Consider a scenario in which a tumor has undergone clonal proliferations, what is the first thing that must occur?
How does the function of cytotoxic agents play a role in the challenges of killing the affected cells?
How does the function of cytotoxic agents play a role in the challenges of killing the affected cells?
Which statement accurately describes the current approach to cancer treatment?
Which statement accurately describes the current approach to cancer treatment?
What strategy is used with combination therapy?
What strategy is used with combination therapy?
What causes most chemotherapies to have adverse effects on normal cells?
What causes most chemotherapies to have adverse effects on normal cells?
What kind of therapy can be used for patients to take advantage of the genetics of cancer cells?
What kind of therapy can be used for patients to take advantage of the genetics of cancer cells?
A cancer cell utilizes multiple mechanisms to evade apoptosis and sustain proliferation. Which of the following integrated strategies would most effectively counteract these survival advantages?
A cancer cell utilizes multiple mechanisms to evade apoptosis and sustain proliferation. Which of the following integrated strategies would most effectively counteract these survival advantages?
A researcher aims to develop a novel therapeutic strategy that selectively eliminates cancer cells while minimizing harm to normal cells. Considering the information, which approach holds the most promise?
A researcher aims to develop a novel therapeutic strategy that selectively eliminates cancer cells while minimizing harm to normal cells. Considering the information, which approach holds the most promise?
To improve the efficacy of chemotherapeutic drugs, scientists are exploring methods to sensitize cancer cells. Which strategy shows the most promise for enhancing chemosensitivity across a broad range of tumors?
To improve the efficacy of chemotherapeutic drugs, scientists are exploring methods to sensitize cancer cells. Which strategy shows the most promise for enhancing chemosensitivity across a broad range of tumors?
A researcher is developing a novel drug to combat cancer metastasis and needs to choose a target that will have the broadest impact. Which of the following targets would most effectively prevent cancer cells from invading tissues and forming metastases?
A researcher is developing a novel drug to combat cancer metastasis and needs to choose a target that will have the broadest impact. Which of the following targets would most effectively prevent cancer cells from invading tissues and forming metastases?
A research team aims to develop a cancer therapy that exploits the unique metabolic requirements of cancer cells. Which strategy aligns best with this objective?
A research team aims to develop a cancer therapy that exploits the unique metabolic requirements of cancer cells. Which strategy aligns best with this objective?
A patient with a solid tumor is undergoing treatment with an anti-angiogenic drug. What is most likely the primary mechanism by which this drug impedes tumor growth and metastasis?
A patient with a solid tumor is undergoing treatment with an anti-angiogenic drug. What is most likely the primary mechanism by which this drug impedes tumor growth and metastasis?
A research team is investigating mechanisms to selectively target and eliminate cancer cells that have developed resistance to multiple chemotherapeutic drugs. Considering the data, which innovative therapeutic approach holds the greatest potential for overcoming drug resistance?
A research team is investigating mechanisms to selectively target and eliminate cancer cells that have developed resistance to multiple chemotherapeutic drugs. Considering the data, which innovative therapeutic approach holds the greatest potential for overcoming drug resistance?
A researcher is investigating a cancer in which cells are highly proliferative, have a compromised DNA repair system, and display chromosomal instability. Which therapeutic strategy would be most effective?
A researcher is investigating a cancer in which cells are highly proliferative, have a compromised DNA repair system, and display chromosomal instability. Which therapeutic strategy would be most effective?
A scientist aims to enhance the delivery of chemotherapeutic agents specifically to tumor cells, which are located far from the bloodstream. Which strategy would be most effective?
A scientist aims to enhance the delivery of chemotherapeutic agents specifically to tumor cells, which are located far from the bloodstream. Which strategy would be most effective?
In designing an effective cancer treatment strategy, researchers aim to target pathways that give cancer cells a survival advantage. Which of the following approaches would counteract the cell's ability to 'evade apoptosis'?
In designing an effective cancer treatment strategy, researchers aim to target pathways that give cancer cells a survival advantage. Which of the following approaches would counteract the cell's ability to 'evade apoptosis'?
A clinician is presented with a patient whose tumor cells have developed multiple mechanisms of resistance to multiple chemotherapy drugs. Which of the following management strategies is the most likely to improve treatment outcomes?
A clinician is presented with a patient whose tumor cells have developed multiple mechanisms of resistance to multiple chemotherapy drugs. Which of the following management strategies is the most likely to improve treatment outcomes?
A new cancer therapeutic approach aims to leverage the body’s own immune system to target malignancies. Which of the following strategies would best align with this therapeutic approach?
A new cancer therapeutic approach aims to leverage the body’s own immune system to target malignancies. Which of the following strategies would best align with this therapeutic approach?
A pharmaceutical company aims to develop drugs that interfere with cancer metastasis. Which molecular target would offer the most promise of directly preventing the spread of cancer cells to distant sites?
A pharmaceutical company aims to develop drugs that interfere with cancer metastasis. Which molecular target would offer the most promise of directly preventing the spread of cancer cells to distant sites?
A researcher is studying the efficacy of combining two chemotherapeutic drugs, Drug A and Drug B, in treating a specific type of cancer. If Drug A is known to cause significant myelosuppression, which principle should guide the selection of Drug B to minimize overlapping toxicities?
A researcher is studying the efficacy of combining two chemotherapeutic drugs, Drug A and Drug B, in treating a specific type of cancer. If Drug A is known to cause significant myelosuppression, which principle should guide the selection of Drug B to minimize overlapping toxicities?
In cancer cells, which characteristic related to the cell cycle offers the most promise as a target for therapeutic intervention, aiming to selectively destroy cancer cells?
In cancer cells, which characteristic related to the cell cycle offers the most promise as a target for therapeutic intervention, aiming to selectively destroy cancer cells?
A patient with ER-positive breast cancer is being treated with tamoxifen. What factor could lead to a lack of response to tamoxifen therapy?
A patient with ER-positive breast cancer is being treated with tamoxifen. What factor could lead to a lack of response to tamoxifen therapy?
A researcher investigates a new anticancer drug that inhibits tubulin polymerization. During which phase of the cell cycle would this new drug be most effective?
A researcher investigates a new anticancer drug that inhibits tubulin polymerization. During which phase of the cell cycle would this new drug be most effective?
If a cancer cell acquires a mutation that disables a key DNA checkpoint, which outcome is most likely to occur?
If a cancer cell acquires a mutation that disables a key DNA checkpoint, which outcome is most likely to occur?
A researcher is studying cancer cells with a mutation that upregulates telomerase activity. What impact does telomerase activation have on cancer cells?
A researcher is studying cancer cells with a mutation that upregulates telomerase activity. What impact does telomerase activation have on cancer cells?
What is the most consequential implication at the cellular level following the inactivation of tumor suppressor genes?
What is the most consequential implication at the cellular level following the inactivation of tumor suppressor genes?
Flashcards
What is cancer?
What is cancer?
A group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.
What is the main feature of cancer?
What is the main feature of cancer?
Uncontrolled cell division arising from an accumulation of several genetic mutations.
Self-sufficiency in growth signals
Self-sufficiency in growth signals
The ability of cancer cells to grow independently of normal growth signals.
What are Oncogenes?
What are Oncogenes?
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What are tumor suppressor genes?
What are tumor suppressor genes?
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What is chromosomal instability?
What is chromosomal instability?
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Describe Dysregulated Cell Cycle
Describe Dysregulated Cell Cycle
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What is the G1 phase?
What is the G1 phase?
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What happens during S Phase?
What happens during S Phase?
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What is the G0 phase?
What is the G0 phase?
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What is a Tumor Initiator?
What is a Tumor Initiator?
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What is a Tumor Promoter?
What is a Tumor Promoter?
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How do oncogenes promote cancer?
How do oncogenes promote cancer?
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What is Aneuploidy?
What is Aneuploidy?
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What is sustained angiogenesis?
What is sustained angiogenesis?
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What’s adenoma?
What’s adenoma?
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What’s carcinoma?
What’s carcinoma?
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What is metastasis?
What is metastasis?
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What is cancer grading?
What is cancer grading?
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what is cancer? Progression
what is cancer? Progression
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What is Chemotherapy?
What is Chemotherapy?
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What are Cell cycle-specific drugs (CCS)
What are Cell cycle-specific drugs (CCS)
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What are Non-cell cycle specific drugs (NCCS)
What are Non-cell cycle specific drugs (NCCS)
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What are 2 examples of genotoxic drugs? (NCCS)?
What are 2 examples of genotoxic drugs? (NCCS)?
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What is a genotoxic drug MOA?
What is a genotoxic drug MOA?
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Name some antimetabolites
Name some antimetabolites
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What kind of drug is Methotrexate frequently used?
What kind of drug is Methotrexate frequently used?
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What is a Cytoskeletal Inhibitor MOA?
What is a Cytoskeletal Inhibitor MOA?
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What is Vincristine/Taxol?
What is Vincristine/Taxol?
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What is a Topoisomerase Inhibitor?
What is a Topoisomerase Inhibitor?
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Names 3 hormonal Therapy drugs
Names 3 hormonal Therapy drugs
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Target is specific in cell
Target is specific in cell
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How does Interferon Help?
How does Interferon Help?
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Where is immuno-oncology going?
Where is immuno-oncology going?
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Vincristine
Vincristine
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What does 5-FU (fluorouracil) do?
What does 5-FU (fluorouracil) do?
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What is resistance?
What is resistance?
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What is increased expression?
What is increased expression?
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What does chemotherapy do?
What does chemotherapy do?
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Describe the affects of Chemotherapy
Describe the affects of Chemotherapy
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Describe type of cancer?
Describe type of cancer?
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What is Chemotherapy failing?
What is Chemotherapy failing?
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Study Notes
Cancer Pharmacology Introduction
- Cancer is a collection of diseases characterized by abnormal cell growth and the potential to invade or spread to other areas of the body
- In Canada, cancer accounted for 26.4% of deaths in 2020
- 239,100 new cases and 86,700 deaths are expected to occur in Canada in 2023
- Lung, colorectal, breast, and prostate cancers will account for approximately half of all cancer diagnoses and deaths in Canada in 2023
- Roughly 1 in 2 Canadians will develop cancer during their lifetime, and 1 in 4 will die from it
- Approximately 63% of Canadians that are diagnosed with cancer will survive for at least 5 years following their diagnosis
- Cancer is primarly a disease of old age
What This Course Will Cover
- Stages of the cell cycle
- Molecular biology of cancers (oncogenes vs tumor suppressors)
- General principles of cancer, pathology, types, stages of tumor progression
- General principles of cancer treatment
- Chemotherapy drugs (cell cycle specific vs non-cell cycle specific)
- Adverse reactions and mechanisms of resistance to chemotherapy
- Pharmacogenomics and individualized therapy
- Chemotherapeutic strategies on the horizon
Learning Objectives
- Explain the difference between normal and cancer cells
- Explain the hallmarks of cancer
- Discuss the cell cycle in detail
- What part of the cell cycle do chemotherapy agents act
- Explain how tumor suppressor genes and oncogenes relate to checkpoint proteins
- Explain ways the cell cycle can be mis-regulated and how this leads to cancer
- Discuss the different types of chemotherapeutics and their function
- Identify chemotherapeutic side-effects that reduce patient quality-of-life
Cancer as a Multi-Step Process
- Cancer requires cells to make critical decisions
- These decisions include, cell renewal, differentiation, and cell death
- These decisions are often not completed properly
The Path To Cancer
- Cancer begins with clonal proliferation, forming from single cell
- Expansion occurs in steps
- Cancer progresses through pre-malignant states (Polyp, MDS, MGUS)
- Accumulation of mutations (Clonal evolution and Resistance)
Hallmarks of Cancer
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis
- Limitless reproductive potential
- Sustained angiogenesis
- Tissue invasion and metastases
- Genomic instability
How Cancer Arises
- Cancer originates from the accumulation of genetic changes including somatic mutations or genetic selection at the level of single cells
- Most cancers have a minimum of 5 gene mutations, but often more(6-9)
- Cancer is generally not a hereditary disease, but dispositions can be inherited
- The BRCA 1/2 mutations can lead to breast and ovarian cancer
- Normal gene activated by ATM kinase and targets p53
- Mutated genes often are involved in regulating the cell cycle
- Genomic instability increases the frequency of cancer
- Aneuploidy is a hallmark of cancerous cells
Etiology: Nature vs Nurture
- Nature : Genetic/Developmental includes inherited cancer syndromes p53, BRCA1/2 and MMR
- Nature also includes immune deficiency syndromes and polymorphisms that influences risk of the occurance, progression and treatment for cancer
- Nurture: Enviromental factors cosmic, fallout, radon/sun, chemotherapy MDS, viruses and bacteria including EBV, HTLV-I/II, H. pylori
- Nurture : Repeated injury, workplace/home and other envrionmental and lifestyle factors
- Enviromental include food additives, pollutions, occupational and industrial
- Lifestyle factors contribute such as tobacco (NSCLC), alcohol (rectal cancer), diet (obesity) and viruses (HPV/HIV)
Cancer Development
- Tumor initiators (Mutagens)
- Include X rays, UV light, DNA alkylating agents
- Tumor promoting actions promote cell proliferation
- Such as inflammation, alcohol, or estrogen and androgens
Cell Cycle Phases
- G1 (gap phase): cell growth and preparation for DNA synthesis
- S (synthesis phase): DNA synthesis
- G2 (second gap phase): cell prepares to divide
- M (mitosis): cell division occurs
- G0 (arrest/quiescent): resting state
Cell Cycle Checkpoints
- G1/S checkpoint: ensures cell size and DNA integrity
- G2/M checkpoint: monitors DNA synthesis and damage
- M checkpoint: monitors spindle formation and attachment to kinetochores
Cancer Pathogenesis: Role of Genes
- Mutations in oncogenes and tumor suppressor genes can lead to cancer
- Oncogenes: activated proto-oncogenes which normally function in cell growth and transcription (myc, ras, src, abl, bcl2)
- Tumor suppressor genes are inactivated and involved in DNA repair, cell cycle control, and cell death (p53, Rb, APC, MEN1, NF1)
Role of Tumour Suppressors
- Tumour Suppressors act as "Guardian(s) of the genome" to maintain genomic integrity, and mutations can lead to a mutator phenotype, increasing mutation rates
- Tumour Suppressors are often the 1st mutation in a developing cancer
- p53 is a classic tumour suppressor
- In 50% of cancers have p53 pathwary mutations
- Also senese genomic damage via ATM
- If its irreparable, p53 will initiate cell death process
- Rb functions as a checkpoint
- Binds to E2F1 that initiates G1/s
- The binding prevents E2F1 from doing its function
OncoGenes
- Oncogenes have a common functions
- Growth: Signal to start replication
- Bypass checkpoints
- Accumulate defects such as improper cell division, DNA contents with improper seperation of chromosomes, and aneuploidy
- growth factors, growth factor receptors, signal transducers, nuclear receptors, transcription factors, suppressors of apoptosis
- HER2/neu, an amplified oncogene that promotes breast cancer is treated though herceptin
- RAS is frequently mutated and responsive to GTPase, mutation leads to expression
- Cancer is not necessarily in only one part of the body. It can move though signaling processes and gene amplification
Genomic Instability
- Chromosomal instability: Gross translocations, Loss and Gain of chromosome parts, detectable genetic abnormalies
- Dysfunctional DNA: Repair is enhanced Gl, Repair genes -Mutator phenotypes ( tumour suppressors) Xeroderma Pigmentosum
- Mismatch repair genes ATM and BRCA1/2
- Philadelphia rearrangement is classic for leukimia
Concepts of Tumor Growth and Nomenclature
- Tumor Growth Concepts depend heavily on Growth fraction and Doubling time
- Early stages : Short doubling/Long doubling times
- Chemotherapy is most effective when the grwoth fractionn is high in tumor grwth
- Benign neoplasms are considered polyp while maglinat ones are known as : eptithelial,mesenchyme( sarcoma(haematopietic and leukemia
Stages of Tumour Development and Terminology
- Hyperplasia: increased number of cells
- Hypertrophy: increased size of cells
- Dysplasia: disorderly proliferation
- Neoplasia: abnormal new growth
- Anaplasia: lack of differentiation
- Tumour : a swelling equated with neoplasia
- Metastatsis: growth of cancer cells at a distance
- Benign/regular while malignant is vice versa with its defined order
- Leiomyosarcoma is a benign, of the Uterus
Cancer Indicators
- GRADE : Cell look ,
- STAGE: the level has spread to(tumour-metastses. nodes /tumour)
Cancer Metastasis and Classification of cancer based on Staging
- Colon can be defined through Dukes A-D and can be categorised by its spread.
- Distant Cancer is hard to eliminate
- Cancer spread throughout the body is caled the primary stage
- Possible therapeutic interventions can be achived through radio,hormonal and specific inhibiors
- Tumour treatments varies on each individuals
Cancers Therapeutic Response
- In the case of Curative Therapies, the treatment options are (CHEmo alone)- chemo+surgery or palliative
- In chemotherapy we aim to shrink the to treat
How Chemotherapy Works
- Chemotheray drug goal are to srink /eliminate,eradict and /or symptom related
- Chemo drugs is evaluated
- CANCER: The fraction of gell/cycling stage detmines effectivness
- Drugs affect the general health of those who come to its side effects
How cancer Affects Us
- Cell replication may have to face tummor as result of cancer
- Side effet has to be in the toxcity (reducinng risk)
- Cell Cycle S and NonS
- AFFECT in the bone marrow, hair, blood and fetus for those those of child bearing
- Chemo is to kill cancer cells by appototosis
CANCER and CCS/NCCS
- CELL CYCLE SPECIIC are G and S and
- NON SPECIFIC DRUGS are what they are named Chemo depends on 2 ways: 1 PHASES/1 DOSE+EFFECT
Classes of AntiCancer Drugs
- Most agents effect normal cells and
- Agents includes Multiple regirnts and optization for PK as well
- Fraction Kill is meant to allow effecticvenes kill. and avoid resistance as treatment is in CYCLES
Fractional Kill and Schedule Dependence
- Phase specic agents/ non speicific agents,
- Tumor heterogenity: Fractional kill is as result of .tumor
Mechanism of Actions and Drug Classes
- Anti Metabol: s PHASE These have been to kill cancer-
- Affect the nucleotide
- Similar molecules as cells
- prevent cell gorwmh and is targeted( RNA-DNA)
Folate Antagonist, Action and uses
- MTX, to be activated , inhibits dihydrofolate r
- Enxymes are target to pyrimides which affects the synthesis
- cell groeth is block, used in lymphtic lekimia.
More on TX
- Inhibit enzymes and has THF analogie
- DNA and runa synthe can in normal and gl/blood
Purine Agonist, Structure and action
- Chemucad to biild RNA
- prevwnt dnar replication
Theiromurine Action
- The 6MP+TG actiiviated in TPMT .
Why TPMT matter
- Important action in bio avialablility
TPMT polymorphism
Polymorphic variations. WW/MM is the one to remiain at all which helps metabolzer
- Mutatiin and toxicity
- Dose of toxicity and relation matters and helps with understanding treatment
Pyrimide antagonists
- Block synthesis and
- Interveens with protein synthesis such as FLU
Chemi-Mitosis
The spindle and function attach into the cell
INHIBITORS are
Microtubule.
Cytonskteleteal
- Paclitazel/Docatel and
- Vinca and vinisidine both inhibits as the side effect
Mechanism of TOPosmerse
- They inhitits the function.and change dna function +structure
Hormone Theraputics ( G1 PHASE)
- STARWE CANCER cell from hormal signal TARGET HORMONE AT target cells
- Breast ovanina and endometrial
Type of Hormone antagonist
- Serums selectove adrogens to target Androgen receptor
Types of Steroids
Receptor estrogen/ and has change or expression , preventting cell divion
- Drugs :tamoxfien, raloxifene
Seruma side Effect is
dependent ,c2d.3
- CYPE Polymorphism , side effetivness
SERUMS is the adnvced stage/tumor
Aromatse is used to
Letrozele side effect to prevent hormone. or drug
The Combinational Thereay
The goal is to find an active agent by itself, or actiive is diff stage
Goal of Multi Drug treatment
- Recruitment/ synchornzation as more specific srategies
- Synergistic effects which decreased taxotiicty or Decrease resistance
- Broader kills (tumour)
- Non hogkin
Non Hodgking and the use
It is an aressive method that utilize combination drug and Rituximb. Cyclo phosphamide, hudroxy and predinsome which limits toxicity
Types of cells and resistance
- Resistance of drugs. to enter cancer cell
Factors involved
Increased expression , in failure or increased
New Gene and The rapoteuc
- Taret spercific enyzmes (kimnases) New generations drugs as well as last resort
How Angiogensis works
It taters the grwoth of endothelial in the tumor w/low
- It is mainly a way in whcih one can use angiogenesis
- Gene based method for drug orradtiations of surgery to attack
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