Introduction to Cancer

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Brief Explanation of the PPT Content

Introduction to Cancer

  • Cancer (Malignant Tumor/Neoplasm): Abnormal cell growth with potential to invade or spread to other parts of the body.
  • Benign Tumors: Do not spread to other parts of the body.
  • Causes of Cancer:
    • Tobacco: Responsible for 22% of cancer deaths.
    • Obesity, Poor Diet, Lack of Physical Activity, Alcohol: Contribute to 10% of cancers.
    • Infections: Hepatitis B, Hepatitis C, and HPV are responsible for 20% of cancers.
    • Genetic Defects: Inherited from parents, responsible for 5-10% of cancers.
  • Detection Methods: Signs, symptoms, screening tests, medical imaging, biopsy.

Cellular Growth Terms

  • Anaplasia: Loss of cell differentiation.
  • Aplasia: Absence of an organ or tissue.
  • Hypoplasia: Below average number of cells.
  • Hyperplasia: Increased number of cells.
  • Neoplasia: Abnormal cell proliferation.
  • Dysplasia: Abnormal growth or development of cells.
  • Metaplasia: Conversion of one cell type to another.
  • Prosoplasia: Development of new cell functions.
  • Desmoplasia: Growth of connective tissue.
  • Atrophy: Reduction in cell size or number.
  • Hypertrophy: Increase in cell size.

Oncogenes and Their Activation

  • Oncogenes: Derived from protooncogenes, become cancerous through mutation.
  • Mechanisms of Activation:
    • Mutation: Changes in the DNA sequence.
    • Overexpression: Increased gene copies leading to higher protein production.
    • Chromosomal Translocation: Exchange of genetic material between chromosomes, often found in cancers like Burkitt lymphoma and CML (Chronic Myelogenous Leukemia).

Specific Oncogenes and Their Pathways

  • C-myc: Found in Burkitt lymphoma, leads to uncontrolled cell proliferation.
  • Bcr-Abl: Fusion protein in CML, causes continuous cell division.
  • Growth Factors and Receptors: EGFR mutations lead to cancers like lung cancer and glioblastoma by promoting uncontrolled cell growth.

JAK-STAT Pathway

  • JAK-STAT Pathway: Involves cytokines or growth factors binding to cell surface receptors, activating JAKs which then phosphorylate STATs, leading to gene transcription in the nucleus.

Ras GTPases

  • Ras GTPases: Function as molecular switches, mutations can lead to continuous activation and cancer.

Serine/Threonine Kinases

  • Raf and PI3K: Involved in cell signaling pathways that regulate growth and survival.
  • PKC (Protein Kinase C): Another important kinase in signaling pathways.

Transcription Factors

  • AP-1: Controls processes like differentiation, proliferation, and apoptosis.
  • NF-κB: Regulates immune responses, linked to cancer, inflammation, and autoimmune diseases.

Summary of Key Points

  • Cancer is characterized by uncontrolled cell growth.
  • Major risk factors include tobacco, infections, and genetic defects.
  • Oncogenes, derived from protooncogenes, can become cancerous through mutations, overexpression, or chromosomal translocations.
  • Specific pathways and proteins like JAK-STAT, Ras GTPases, and serine/threonine kinases play crucial roles in cell signaling and cancer development.
  • Growth factors and their receptors, as well as transcription factors like AP-1 and NF-κB, are vital in the regulation of cell growth and survival.

 

Study Notes

Introduction to Cancer

  • Cancer (Malignant Tumor/Neoplasm): Abnormal cell growth with potential to invade or spread.
  • Benign Tumors: Do not spread.
  • Causes:
    • Tobacco: 22% of cancer deaths.
    • Obesity, poor diet, lack of physical activity, alcohol: 10%.
    • Infections (Hepatitis B/C, HPV): 20%.
    • Genetic defects: 5-10%.
  • Detection: Signs, symptoms, screening tests, medical imaging, biopsy.

Types of Cellular Growth

  • Anaplasia: Loss of structural differentiation.
  • Aplasia: Missing organ/part.
  • Hypoplasia: Below-average number of cells.
  • Hyperplasia: Increased cell proliferation.
  • Neoplasia: Abnormal cell proliferation.
  • Dysplasia: Change in cell/tissue phenotype.
  • Metaplasia: Conversion to a different cell type.
  • Prosoplasia: Development of new cell function.
  • Desmoplasia: Connective tissue growth.
  • Atrophy: Reduced functionality due to decreased cell volume/number.
  • Hypertrophy: Increased cell volume.

Oncogenes

  • Oncogenes: Derived from protooncogenes, mutated to promote cancer.
  • Characteristics: Form foci, grow without matrix, form tumors in immunocompromised animals.
  • Activation Mechanisms:
    • Mutation
    • Overexpression (gene amplification)
    • Chromosomal translocation

Gene Amplification

  • Gene Amplification: Expansion of gene copies, leading to drug resistance.
  • Chromosomal Rearrangements: Lead to hematologic malignancy via protooncogene activation or fusion genes.

Specific Oncogenes and Mechanisms

  • C-myc Translocations: Involved in Burkitt lymphoma.
  • Bcr-Abl Oncogene: Found in chronic myelogenous leukemia (CML), causes uncontrolled proliferation.
  • Growth Factors and Receptors: Stimulate cell growth via receptors like EGFR, mutations lead to uncontrolled growth.

Pathways and Signaling

  • JAK-STAT Pathway: Involved in cellular responses, activated by cytokines/growth factors.
  • Ras GTPases: Regulated by GTP/GDP binding, mutations lead to uncontrolled signaling.
  • Serine/Threonine Kinases: Include Raf, PI3K, PKC, involved in signaling pathways.

Transcription Factors as Oncogenes

  • AP-1, c-myc, STAT, NF-kB: Control various cellular processes, dysregulation leads to cancer.

Quiz Questions and Answers

  1. What is the primary difference between benign and malignant tumors?

    • Answer: Benign tumors do not spread to other parts of the body, whereas malignant tumors have the potential to invade or spread to other parts of the body.

  2. List three major causes of cancer-related deaths.

    • Answer: Tobacco use, obesity and poor diet, and infections such as Hepatitis B and HPV.

  3. What percentage of cancers are caused by genetic defects inherited from parents?

    • Answer: Approximately 5-10%.

  4. Define hyperplasia and neoplasia.

    • Answer: Hyperplasia is the proliferation of cells, resulting in an increased number of cells. Neoplasia is the abnormal proliferation of cells, often forming a mass or tumor.

  5. What are oncogenes and how do they originate?

    • Answer: Oncogenes are mutated forms of protooncogenes that promote cancer by driving cell proliferation or reducing sensitivity to cell death.

  6. Describe two mechanisms of oncogene activation.

    • Answer:
      1. Mutation: Changes in the DNA sequence of a protooncogene.
      2. Overexpression: Amplification of the protooncogene, leading to increased gene copies within the cell.

  7. What is gene amplification and how does it contribute to cancer?

    • Answer: Gene amplification is the expansion of the number of copies of a gene within the genome, leading to increased expression of genes, which can confer a growth advantage to cancer cells.

  8. Explain the role of C-myc translocations in Burkitt lymphoma.

    • Answer: C-myc translocations involve the movement of the c-myc gene to a location near antibody genes, leading to uncontrolled expression of c-myc protein and uncontrolled cell proliferation.

  9. What is the function of the Bcr-Abl oncogene in chronic myelogenous leukemia (CML)?

    • Answer: The Bcr-Abl oncogene produces a fusion protein that promotes uncontrolled cellular proliferation, reducing the dependency on growth factors and altering adhesion properties.

  10. How do growth factors stimulate tumor cell growth?

    • Answer: Growth factors bind to specific receptors on the cell surface, initiating signaling pathways that promote cell proliferation and survival.

  11. Describe the JAK-STAT pathway and its significance in cancer.

    • Answer: The JAK-STAT pathway involves cytokines or growth factors binding to cell surface receptors, activating JAKs, which then phosphorylate STATs. The phosphorylated STATs dimerize and translocate to the nucleus to induce gene transcription. Dysregulation of this pathway can lead to cancer.

  12. What role do Ras GTPases play in cell signaling?

    • Answer: Ras GTPases act as molecular switches in signaling pathways, regulating cell proliferation and survival. Mutations in Ras can lead to continuous activation and uncontrolled cell growth.

  13. Name two serine/threonine kinases involved in cancer pathways.

    • Answer: Raf and PI3K are serine/threonine kinases involved in cancer pathways.

  14. Explain the function of transcription factors AP-1 and NF-kB in cancer.

    • Answer:
      • AP-1 regulates cellular processes such as differentiation, proliferation, and apoptosis. Dysregulation can promote cancer.
      • NF-κB controls DNA transcription, cytokine production, and cell survival. Aberrant activation is linked to cancer and inflammatory diseases.

  15. What is the significance of NF-κB in regulating immune responses and its link to cancer?

    • Answer: NF-κB plays a key role in the immune response to infection. Incorrect regulation can lead to cancer, inflammatory, and autoimmune diseases.

  16. How does the EGFR receptor contribute to cancer when mutated?

    • Answer: Mutations in EGFR can lead to its overexpression, causing uncontrolled cell proliferation and contributing to cancers such as lung cancer and glioblastoma.

  17. What are the main steps involved in the JAK-STAT signaling mechanism?

    • Answer:
      1. Ligand binding and receptor dimerization.
      2. JAK transphosphorylation.
      3. Phosphorylation of receptor tyrosines.
      4. STAT binding and phosphorylation.
      5. STAT dimerization and nuclear translocation.
      6. Gene transcription.

  18. Define the term 'protooncogene' and give an example.

    • Answer: Protooncogenes are normal genes that promote cell growth and division. When mutated, they become oncogenes. Example: c-myc.

  19. What is the impact of gene fusion in cancer, particularly in the case of Bcr-Abl?

    • Answer: Gene fusion, such as Bcr-Abl in CML, results in the production of a chimeric protein with unregulated kinase activity, promoting cellular proliferation and reducing growth factor dependency.

  20. How do SH2 and SH3 domains contribute to Src kinase activity?

    • Answer: SH2 domains bind phosphorylated tyrosines, and SH3 domains interact with proline-rich regions. These interactions potentiate signal transduction and regulate Src kinase activity.

Fill in the Blank Questions

  1. Cancer, also known as a __________ tumor, involves abnormal cell growth with the potential to invade or spread to other parts of the body.

    • Answer: malignant

  2. __________ tumors do not spread to other parts of the body.

    • Answer: Benign

  3. Tobacco use accounts for ______% of cancer deaths.

    • Answer: 22

  4. Approximately 5-10% of cancers are due to genetic defects __________ from a person's parents.

    • Answer: inherited

  5. Hyperplasia refers to the __________ of cells.

    • Answer: proliferation

  6. Neoplasia is an abnormal __________ of cells, often forming a mass or tumor.

    • Answer: proliferation

  7. Oncogenes are derived from normal host genes called __________.

    • Answer: protooncogenes

  8. Gene amplification refers to the expansion in __________ number of a gene within the genome of a cell.

    • Answer: copy

  9. Chromosomal translocations can lead to the formation of __________ genes in cancer cells.

    • Answer: fusion

  10. The __________ oncogene is commonly found in Burkitt lymphoma.

    • Answer: c-myc

  11. The Bcr-Abl fusion protein is associated with __________ myelogenous leukemia (CML).

    • Answer: chronic

  12. Growth factors stimulate cell growth by binding to specific __________ on the cell surface.

    • Answer: receptors

  13. The JAK-STAT pathway is activated by __________ or growth factors binding to cell surface receptors.

    • Answer: cytokines

  14. Ras GTPases are active when bound to __________ and inactive when bound to GDP.

    • Answer: GTP

  15. Serine/threonine kinases, such as Raf and PI3K, are involved in __________ pathways.

    • Answer: signaling

  16. Transcription factor AP-1 is composed of proteins belonging to the __________ and c-Jun families.

    • Answer: c-Fos

  17. The NF-κB protein complex controls __________ of DNA, cytokine production, and cell survival.

    • Answer: transcription

  18. The EGFR receptor, when mutated, can lead to uncontrolled cell __________.

    • Answer: proliferation

  19. JAK proteins contain a __________ domain that is vital for their kinase activity.

    • Answer: kinase

  20. NF-κB signaling can be inhibited by the drug __________, which is approved for the treatment of Mantle Cell Lymphoma and Multiple Myeloma.

    • Answer: Bortezomib

Multiple Choice Questions

  1. What is the primary characteristic of malignant tumors?

    • A) They do not spread to other parts of the body.
    • B) They have the potential to invade or spread to other parts of the body.
    • C) They are always genetic.
    • D) They are caused by infections.
    • Answer: B

  2. What percentage of cancer deaths is attributed to tobacco use?

    • A) 10%
    • B) 15%
    • C) 22%
    • D) 30%
    • Answer: C

  3. Approximately what percentage of cancers are due to inherited genetic defects?

    • A) 5-10%
    • B) 15-20%
    • C) 25-30%
    • D) 35-40%
    • Answer: A

  4. Which of the following terms refers to the proliferation of cells?

    • A) Anaplasia
    • B) Aplasia
    • C) Hyperplasia
    • D) Dysplasia
    • Answer: C

  5. What are oncogenes derived from?

    • A) Normal host genes called protooncogenes
    • B) Foreign DNA
    • C) Viral infections
    • D) None of the above
    • Answer: A

  6. Which mechanism does NOT activate oncogenes?

    • A) Mutation
    • B) Overexpression
    • C) Gene suppression
    • D) Chromosomal translocation
    • Answer: C

  7. Gene amplification refers to the expansion in __________ of a gene within the genome of a cell.

    • A) Size
    • B) Copy number
    • C) Function
    • D) Location
    • Answer: B

  8. The c-myc oncogene is commonly found in which type of cancer?

    • A) Breast cancer
    • B) Burkitt lymphoma
    • C) Lung cancer
    • D) Skin cancer
    • Answer: B

  9. The Bcr-Abl fusion protein is associated with which leukemia?

    • A) Acute lymphoblastic leukemia
    • B) Chronic myelogenous leukemia
    • C) Hairy cell leukemia
    • D) T-cell leukemia
    • Answer: B

  10. Which of the following best describes growth factors?

    • A) Molecules that inhibit cell growth
    • B) Molecules that stimulate cell growth
    • C) Molecules that bind DNA
    • D) Molecules that destroy cancer cells
    • Answer: B

  11. The JAK-STAT pathway is primarily activated by which molecules?

    • A) Hormones
    • B) Cytokines
    • C) Enzymes
    • D) Antibiotics
    • Answer: B

  12. Ras GTPases are active when bound to which molecule?

    • A) ATP
    • B) GDP
    • C) GTP
    • D) ADP
    • Answer: C

  13. Which of the following are serine/threonine kinases involved in cancer pathways?

    • A) EGFR and HER2
    • B) Raf and PI3K
    • C) c-myc and Bcl-2
    • D) APC and p53
    • Answer: B

  14. Which proteins are components of the AP-1 transcription factor complex?

    • A) c-Fos and c-Jun
    • B) EGFR and HER2
    • C) Bcl-2 and Bax
    • D) APC and β-catenin
    • Answer: A

  15. NF-κB is involved in regulating which processes?

    • A) Apoptosis and cell division
    • B) DNA transcription and cell survival
    • C) Hormone synthesis and metabolism
    • D) Protein folding and degradation
    • Answer: B

  16. Mutations in which receptor are commonly associated with lung cancer and glioblastoma?

    • A) HER2
    • B) EGFR
    • C) PDGFR
    • D) VEGFR
    • Answer: B

  17. Which domain is crucial for the kinase activity of JAK proteins?

    • A) SH2 domain
    • B) Kinase domain
    • C) FERM domain
    • D) Pseudokinase domain
    • Answer: B

  18. Which drug is approved for the treatment of NF-κB driven Mantle Cell Lymphoma and Multiple Myeloma?

    • A) Imatinib
    • B) Bortezomib
    • C) Sorafenib
    • D) Gefitinib
    • Answer: B

  19. Which of the following best describes protooncogenes?

    • A) Normal genes that can become oncogenes due to mutations
    • B) Genes responsible for apoptosis
    • C) Genes that repair DNA damage
    • D) Genes that inhibit cell growth
    • Answer: A

  20. What are the SH2 and SH3 domains important for in Src kinase activity?

    • A) Binding to DNA
    • B) Promoting protein/protein interactions
    • C) Degrading proteins
    • D) Binding to ATP
    • Answer: B

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