Anti-Neoplastic Drugs, Pt. 2 Flashcards
What 4 dog breeds are at the highest risk of developing cancer? What kind of cancer is each most susceptible to?
- Boxers - lymphoma, lymphosarcoma, brain tumors, mast cell tumors
- Golden Retrievers - hemangiosarcoma, lymphoma
- Bernese Mountain Dogs - lymphoma, lymphosarcoma
- Rottweilers - lymphoma, bone cancer, soft tissue sarcoma, blader carcinoma, angiosarcoma
What 5 environmental factors contribute to the development of cancer?
- UV rays (sun)
- chemical carcinogens (herbicides, insecticides, pesticides)
- asbestose, cadmium, vinyl chloride, benzene, uranium, nickel
- second-hand tobacco smoke
- air pollution
Why does advanced age predispose to cancer?
- weakening of the immune system
- longer exposure to environmental carcinogens
What 2 types of viruses have been linked to cancer development?
- FeLV - lymphoma
- papilloma virus - oral papilloma in dogs
What type of cancer is sexually transmitted in dogs? What can be caused by vaccination?
canine transmissible venereal tumor
injection site sarcomas
What is squamous cell carcinoma associated with?
UV light in white (unpigmented skin) cats, dogs, and horses
What are the 3 causes of cancer on the genetic level?
- SPORADIC (90%) - accumulation of mutations in somatic cells over a lifetime with development at older age and in certain cells
- HEREDITARY (5-10%) - inherited susceptibility through germline mutation giving the tumor a “head start” allowing it to develop at a younger age
- RANDOM ERRORS (66%) - environmental factors multiply errors
What is the point to understanding the type of mutation a patient has that is causing their cancer?
affects treatment —> find the mutation that is driving tumor and inhibit the pathway to slow down or stop tumor growth
What 2 groups of genes have been linked to serious mutations that cause hereditary cancer risk?
- BRCA1 and BRCA2 - DNA repair molecules responsible for genetic stability (typically only passed on from one parent, since an embryo with 2 mutated copies would likely die)
- p10 and p53 - tumor suppressor genes
What cat breed is most susceptible to developing cancer? What 3 types?
Siamese
- lymphoma
- lymphosarcoma
- thymoma
What is the molecular basis of cancer?
cancer is a cell growth disease where cells undergo division many more times than normal, making the cells prone to replication errors accumulating mutations that are not repaired
How do normal cells usually maintain homeostasis?
- growth factors induce cell proliferation
- death signals induce controlled cell death (apoptosis)
homeostasis balances cell proliferation and cell death
How do normal cells become cancerous?
unbalanced proliferation and apoptosis leads to survival of cells with mutations that are able to accumulate
How does the disruption of normal tissue homeostasis cause cancer?
- overexpressed oncogenes induce proliferation of cancer cells and tumor formation
- inhibition, mutation, or mutation of tumor suppressor genes (p53, p10) block apoptosis of cancer cells
What are the 5 stages of the cell cycle?
- G0 = resting
- G1 = growth
- S = DNA synthesis
- G2 = growth and preparation for mitosis
- M = mitosis (cell division)
What are checkpoints? Which 4 exist in the cell cycle?
control mechanisms in cells that ensure proper division
- DNA damage checkpoint at the end of G1
- DNA damage checkpoint in the middle of S
- DNA replication and damage checkpoint at the end of G2
- spindle assembly formation at the beginning of M
What happens during checkpoint failure?
genetic instability, which is a major factor in the development of cancer
What forms the DNA damage and replication checkpoints? What are 2 examples?
network of proteins
- cyclins
- cyclin-dependent kinases (Cdks)
Carcinogenesis and DNA damage:
cancer is most common in proliferative tissues where the increased turn-over leads to more chances of mutations
What is the Cental Dogma of Molecular Biology?
DNA is transcripted into mRNA, which is translated into protein
(at each level something can go wrong and allows for cancer drug targeting)
What are the 2 types of nitrogenous bases?
- PURINES = double-ring structure
- adenine
- guanine - PYRIMIDINES = single-ring structure
- thymine
- uracil
- cytosine
What must happen before a cell can divide? What will each new DNA molecule consist of?
DNA in the nucleus must be duplicated
one old strand and a new complementary strand
How do helicases and DNA polymerases function in DNA replication?
HELICASE = unzips double-stranded DNA
DNA POLYMERASE = adds complementary nucleotides to the unwound DNA
What do topoisomerases do? What 2 partake in DNA replication?
overwinding or underwinding of DNA (act on 3D topology of DNA
- TOPOISOMERASE I: cut and religate single DNA strand of double helix
- TOPOISOMERASE II: cut both strands of DNA double helix
What is DNA damage? What are the 6 types?
alteration of DNA, which is the aim in cancer treatment (DNA damage-inducing drugs block DNA repair in cancer cells)
- single-strand break
- mis-match
- damaged base
- double-strand break
- intra-strand crosslink
- inter-strand crosslink
What do BRCA1 and BRCA2 do?
promote efficient and precise repair of mis-match and double-stranded breaks
(germline mutation = accumulation of DNA damageand neoplastic transformation)
What are the 6 types of anti-cancer therapy?
- chemotherapy - cytotoxic, DNA damage
- targeted therapy - monoclonal antibody against over-expressed oncogenes, small molecules
- endocrine therapy - estrogen receptors, androgen receptors, hormones
- immune therapy - immune system activation
- epigenetic therapy - DNA methylation, histone acetylation
- chemoprevention - dietary products and supplementation
What are the 3 major challenges to anti-cancer therapy?
- need to develop new targeted and tailored therapies
- chemoprevention
- combination therapies need to have synergistic efficacy and minimum toxicity
Why do chemotherapeutic drugs typically cause adverse effects?
cannot distinguish between cancer cells and normal cells
How are cancers categorized? What is necessary to do this? What causes the low overall therapy success in the past 3 decades?
tissues of origin and stages in clinical progression - histopathology
distinct subcategories within one cancer with different molecular signatures —> can’t treat all breast cancers the same
What 2 types of cancer are most commonly treated with endocrine therapy?
- breast cancer
- prostate cancer
targets estrogen and androgen receptors
What are the best steps for chemoprevention?
dietary products and supplementation
- better to prevent cancer than treat it
