Introduction: Cancer Pathogenesis Flashcards
Epigenetics
Changes in gene expression that occult WITHOUT altering the DNA sequence
Hyperplasia
-Rapid proliferation rate
-Number of cells increasing
Hypertrophy
-Increase in size (bigger size)
Metaplasia
-Conversion of mature normal cells to a different distinct mature cell
-Change
Dysplasia
Normal cell to immature abnormal cell
-Disordered
What is the transition from normal state to cancer?
1) Normal
2) Hyperplasia
3) Dysplasia
4) Cancer
What are the four main carcinogenesis phases during neoplastic development?
- Initiation (Carcinogen/UV)
- Promotion (Tumor promoter/UV)
- Progression
- Metastasis
What happens during the initation phase of neoplastic development?
Irreversible genetic mutation in stem cell/progenitor cell
What happens during the Promotion phase of neoplastic development?
- Clonal expansion of initiated cells within generalized hyperplasia
- Outgrowth of pre-malignant tumors = papillomas
What happens during the Progression phase of neoplastic development?
Malignant conversion to invasive carcinoma
T/F: Chemical carcinogens are linked to specific cancers
T
What is the mechanism of carcinogenic hormones or pharmaceutical agents?
-Irreversible DNA damage (mutagenic; initiation)
-Promoting agent leading to cell proliferation
What is the mechanism of biologic agent?
There are viral proteins that are going to interact with certain genes that are going to be your tumor suppressor genes and your oncogenes. The combined effect will lead to this uncontrolled self-growth
What are cancer’s seven warning signs?
- Change in bowel or bladder habits
- **A sore that does not heal
- Unusual bleeding or discharge**
- Thickening or lump in the breast or elsewhere
- Indigestion or difficulty in swallowing
- Obvious change in want or mole
- Nagging cough or hoarseness
What are cancer’s warning signs in children?
- **Continued, unexplained weight loss
- Headaches with vomiting in the morning**
- Lump or mass in abdomen, neck, or elsewhere
- Development of a whitish appearance in the pupil of the eye
- Recurrent fevers not caused by infections
- Excessive bruising or bleeding
- **Noticeable paleness or prolonged tiredness
- SOB**
What is used to describe the cancer and its progression?
Grading and staging
Gleason’s Pattern
-
Grading describes how the cancer look compared to normal, healthy cells
-How fast cancer grows (proliferation)
Staging
Refers to size and spread of the cancer
What are the exceptions in the naming system of tumors?
- Lymphoma - malignant tumor from lymphocyte
- Mesothelioma - malignant tumor from the mesothelium
- Seminoma - malignant germ cell tumor
What is the prefix of fat?
Lipo
What is the prefix of fibrous tissue?
Fib
What is the prefix of cartilage?
Chondro
What is the prefix of blood vessel?
Hemangio
What is the prefix of smooth muscle?
Leiomyo
What is the prefix of striated muscle?
Rhabdomyo
What is the prefix of gland?
Adeno
How is cancer classified?
- By type of tissue in which the cancer originates (histological type)
- By the primary site, or the location in the body where the cancer first developed
What are the 7 major categories of histological type?
- Carcinoma
- Sarcoma
- Myeloma
- Blastoma
- Leukemia
- Lymphoma
- Mixed Types
Carcinoma
Malignant neoplasm of epithelium origin or cancer of the internal or external lining of the body
Sarcoma
Cancer that originates in supportive and connective tissues such as bones, tendons, cartilage, muscle, and fat
Myeloma
Cancer that originates in the plasma cells of bone marrow
Blastoma
Cancers derived from immature “precursor” cells or embryonic tissue
Leukemia
Cancers of the bone marrow
Lymphoma
Solid cancers that develop in the glands or nodes of the lymphatic system
Mixed Types
Cancers with histological features of at least two different types of cancer
What are the two staging systems used to communicate the extent and severity?
TNM staging and overall stage grouping
TNM staging system
- Tumor: size and extent of the main tumor
- Nodal status: the number of nearby lymph nodes that have cancer
- Metastasis: whether the cancer has metastasized
T/F: The Overall Grouping system is more detailed than the TNM system
F; less detailed
Germline genetic variant
- Genetic variants present in egg or sperm
- Can be inherited
- All cells carry the variant
- Can influence the pharmacokinetics of drugs (e.g., cell uptake, metabolism or elimination)
Somatic genetic variant
- Occurs in non-germline tissues
- Not inherited - only tumor carries the variant
- Require comparing somatic tissue to germline
- Can be linked to prognosis or drug resistance
Receptor tyrosine kinases
Ligand binding creates signals for cell growth and differentiation
Cytoplasmic tyrosine kinases
Transduce signals involved in cell proliferation, migration, differentiation, and survival
Serine/threonine kinases
Involved in organism development, cell cycle regulation, cell proliferation, differentiation, cells survival, and apoptosis
GTPase signaling
Play role in signal transduction and cell division
What is the protein function in tumor suppressor genes?
- Cell cycle arrest and apoptosis in response to DNA damage
- Protein phosphatase
- Inhibitors of growth-promoting signal transduction
- Ubiquitin ligase; protein stability
- Regulator of the cell cycle (master brake)
- Involve in cell adhesion and migration
- DNA repair
T/F: Multiple mutations are required to inactivate tumor suppressor genes
T
Knudson Hypothesis
Cancer is the result of accumulated mutations to a cell’s DNA
* Not all mutations drive cancer or provide growth advantage
