Cancer Biology Profile of a Cancer Cell Part-2

Study Notes

Cancer Biology Profile of a Cancer Cell Part-2

The lecture covers the traits of cancer cells, cancer cells and the cell cycle, cancer cells and apoptosis, cancer cells and DNA damage, tumor immunology, molecular changes in cancer cells, and repair pathways.
Objectives include cancer cells and DNA damage, tumor immunology, molecular changes in cancer cells.
Mutations in DNA are spontaneous or due to exposure to mutation-causing agents in the environment.
Types of mutations include physical mutations (ionizing radiations, non-ionizing radiations, heat) and chemical mutagens (alkalizing agents, deaminating agents, intercalating agents).
Examples of physical mutagens include gamma rays, X-rays, UV rays, alpha particles, beta particles, and fast neutrons, while chemical mutagens include halouracil, mitomycin, proflavine, sodium azide, nitrosoguanidine, nitrogen mustard, ethyl methyl sulfate, uridine derivatives, hydroxyl amine, diethyl sulfate, acridine orange, and nitrous acid.
Common DNA damage includes depurination (loss of adenine or guanine) and deamination (removal of a base's amino group).
Ultraviolet radiation causes covalent bonds to form between adjacent pyrimidine bases, most commonly thymine dimers.
Repair pathways for DNA damage include:
- Direct repair: using a photolyase enzyme in organisms that absorbs visible light to cleave the thymine dimer.
- Proofreading repair: DNA polymerase corrects mismatched bases.
- Excision repair:
  - Base excision repair corrects single damaged bases (e.g., DNA glycosylases remove deaminated bases).
  - Nucleotide excision repair removes pyrimidine dimers and other lesions (e.g., NER endonuclease enzyme).
Xeroderma pigmentosum is caused by mutations in genes coding for components of the NER system. People with this condition have an extremely high risk of developing skin cancer.
Mismatch repair is critical for maintaining DNA
- Mismatch repair system excises the new strand in any region
- This procedure uses the original strand as a template.
Postreplication repair and SOS Repair
- Occurs when DNA replication skips over a lesion; e.g a thymine dimer
- Involves recombination of the parental strand
- SOS repair is a global cellular response to DNA damage in bacteria.
Nonhomologous end-joining and homologous recombination
- Repair for double-strand breaks
  - Nonhomologous end-joining joins DNA fragments directly -Error-prone, as it cannot prevent loss of nucleotides or prevent DNA fragments from different chromosomes from being joined.
  - Homologous recombination utilizes a homologous chromosome copy as a template.
    - A more precise repair mechanism.
Women who inherit mutations in BRCA1 or BRCA2 have a high risk of breast and ovarian cancer.
Cancer cells exhibit genetic instability, often being aneuploid. aneuploidy generally involves both the loss of some chromosomes and an extra copies of other chromosomes.
The Philadelphia chromosome is found in nearly 90% of people with chronic myelogenous leukemia with DNA breakage and reciprocal exchange. This translocation produces the BCR-ABL fusion gene. The immune system can protect against cancer. However, there is no adequate immune response due to certain tumor cells' tactics in evading the immune response.
Immune cells can present and attack antigens or kill cells.
Cancer cells produce various antigens including tumor-specific
- Unique to tumor cells, and not found in normal cells,
- Can induce responses leading to tumor rejection
Tumor-associated antigens
- Expressed on normal and tumor cells
- Do not generally induce tumor rejection
MAGE antigens are expressed in some cancers and not in most normal tissues that are close to being tumor-specific.
Cancer vaccines can consist of synthetic MAGE peptides to induce immune responses.
Cancer cells can evade the immune response by producing molecules that kill lymphocytes, forming surrounding tissue to shield them from immune attack, or dividing quickly.
Cancer cells have reduced gap junctions, altered clump tendencies in the presence of lectins, and diminished or missing E-cadherin, which is related to cell-to-cell communication.
Cancer cells produce embryonic proteins (e.g., alpha-fetoprotein, carcinoembryonic antigen) and hormones (e.g., chorionic gonadotropin, placental lactogen) which can serve as markers or stimulate blood vessel growth.