Anticancer Pharmacology Flashcards
Cancer
Uncontrolled proliferation and spread of abnormal cells by invading tissues, lymph nodes, and organs
Metastasis
Causes cancers at other sites in the body by spreading. Locations such as the lymph nodes, bone, liver, brain, lungs, etc.
What are the two types of cancer?
- Solid cancer - tumor
- Hematological cancer - blood cancer
Give 1 occupational cause example and what part of the body it affects
Asbestos; lung
What does ultraviolet radiation cause?
Melanoma (skin cancer)
Which body part does alcohol affect?
Liver
Which body part does tobacco affect?
Lung
Which body part is affected by dietary choices?
Colon; high saturated fat and red meat can negatively impact the colon
Which does ionizing radiation (uranium deposits) cause?
Leukemia
Give 1 example of a virus and which body part it affects
HPV (human papillomavirus); Cervix
Give 1 example of how genetics play a role in causing cancer
The presence of both the BRCA1 and BRCA2 gene significantly increases the chances of breast cancer
Give 1 example an alkylating agent and 2 parts of the body that it can cause cancer in
Melphalan; blood (leukemia) and bladder
What is the purpose of diagnosis and staging?
Diagnosis: Tissue biopsy and pathological assessment.
We cannot diagnose cancer unless the cells are viewed under a microscope
Staging: Determines how widespread cancer is
How do you classify how widespread the cancer is?
TNM staging of solid tumours:
T = size of primary tumour
N = absence/presence and extent of regional lymph node metastasis (if present, then it may have gone past the local zone)
M = absence/presence of distant metastasis (if present, then there is evidence it has spread to other organs/tissues - stage IV cancer)
MOA of chemotherapy
Damages and interferes with DNA synthesis, causing cancer cell death
It can be phase specific (G1, S, G2, M) or non-phase specific
With this treatment, most cytotoxic cells (immune cells) are undergoing rapid division
What is the purpose of combination chemotherapy and what are the 4 factors an agent needs?
Since cancer cells are genetically unstable and have tumour masses of heterogeneous cells, this type of chemo has a broader coverage against resistant cells and can get rid of different cell lines
- Demonstrable single-agent activity
- Different MOA
- Devoid of overlapping toxicities
- Optimal dose and schedule
Why does chemotherapy fail?
Drug resistance:
1. Increases with increased tumour size
2. Can be acquired or inherited
3. Can become multidrug resistance
(note: the cells can grow resistance through evolution)
4 mechanisms of drug resistance
- Improves proficiency in DNA repair
- Inactivates cancer drug by: decreasing cellular uptake of the drug and increasing efflux of the drug
- Change in biochemical pathways
- Change target enzymes
MOA and an example of alkylating agents
Bind DNA by creating covalent bonds → cross-link DNA → prevent unwinding of DNA molecule → less protein synthesis
Cyclophosphamide, melphalan
MOA and an example of Epipodophyllotoxins
Inhibit topoisomerase II (responsible for DNA breaks) → inhibit DNA synthesis
Etoposide
MOA and an example of Taxanes
Promote assembly and stabilization of microtubules → inhibit cell replication
May inhibit angiogenesis (blood vessel formation that cancer can use to spread throughout the body)
Docetaxel
MOA and an example of Antimetabolites
Resemble naturally occurring nuclear structural components (eg. nucleotide bases) → incorporate into DNA/RNA → inhibit function/synthesis
5-Fluorouracil (5-FU)
MOA and an example of Anti-tumor Antibiotics
Insert b/w DNA base pairs → uncoil DNA helix→ inhibit DNA/RNA synthesis. May also inhibit polymerase
Doxorubicin
MOA and an example of Alkylating Agent + Anti-tumour Antibiotic
Undergoes spontaneous decomposition → reactive methylcarbonium ions → alkylate DNA → interstrand cross links → inhibit mitosis
Streptozocin
MOA and an example of Camptothecins
Bind topoisomerase I (responsible for reversible, single-strand DNA breaks during DNA replication) → prevent religation of DNA strand → cell death
Irinotecan
MOA and an example of Vinca Alkaloids
Prevent polymerization of tubulin to form microtubules + depolymerizes formed tubules → inhibit mitosis
Vincristine
MOA of Immunotherapy
Immune Checkpoint Inhibitors - Take ‘brakes’ off immune system → helps it to recognize & attack cancer cells
An example of Targeted Therapy
Monocolonal Antibodies target a receptor
Ex. Trastuzumab (Herceptin): Anti-HER2
An example of Endocrine Therapy
Aromatase Inhibitors: Letrozole
10 common side effects of treatment
- Febrile neutropenia (fewer neutrophils → fever)
- Anemia (few red blood cells)
- Thrombocytopenia (few #platelets = increase risk of bleeding)
- Mucositis/stomatitis (kill mucus/stomach cells → sores)
- Nausea & vomiting
- Diarrhea/constipation
- Weight loss
- Fatigue
- Alopecia
- Infertility
4 examples of screening tests
- Colorectal - Colonoscopy
- Breast - Mammography
- Cervix - Pap Smear
- Skin - Dermatology Screening
