intro to cancer chemotherapy Flashcards
what are the most common cancer treatments?
surgery, radiation, chemotherapy
what is the goal of anticancer drugs and what are the overall moa’s of anticancer drugs
- goal is to destroy cancer cells
- single drug or combo of drugs used alone or in addition to surgery/radiation
- anticancer drugs target proliferation of cells and interfering with cancer mechanisms can provide treatment
what are the types of cancer?
- Carcinomas = cancers of epithelial cells lining the surface of organs
80 - 90 % of cancers are carcinomas:
epithelial cells = site of extensive cell proliferation and frequent exposure to chemical/physical damage - Sarcomas = cancers of muscle, bone, cartilage, fat, connective tissue
- Leukemia = group of blood cancers, usually originate in bone marrow resulting in underdeveloped blood cells
- Lymphoma = group of cancers that develop from lymphocytes
- Blastoma = cancers that develop from precursor cells or embryonic tissue
what is cancer?
- group of diseases
- cells exhibit uncontrolled growth/proliferation
and have the potential to invade surrounding tissue and sometimes colonize in other locations in the body (metastasis)
where does cancer originate?
- need a triggering event, need events that will cause its promotion, then the cell needs to invade tissue to be malignant
- Most cancers originate from single aberrant cell
- genetic = change in DNA
- epigenetic = change in gene expression without change in DNA sequence
- Normal mutation rate = 10^10 / gene / life-time
- single mutation not enough to → cancer
- requires several independent changes in cell lineage
what does tumour progression depend on?
- mutation/epigenetic alteration rate
- selective advantage
- proliferation rate (how quickly cells divide)
- invasiveness (how cells migrate into tissue)
critical cancer genes:
- DNA proofreading/repair genes (if mutations in repair genes, this can be passed onto daughter cells)
- genes maintaining chromosomal integrity
- oncogenes (ability to promote or inhibit cancer growth)
- tumour suppressor genes (ability to promote or inhibit cancer growth)
what happens with a mutation in a gene regulating DNA repair?
- genetically unstable cells less fit therefore additional mutations in genes regulating cell death, differeniation or divison required
- inherited mutations increase the risk of developing cancer
- does not mesn everyone with a mutation will get cancer just increases the risk
what is oncogene?
Oncogene (gain of function)
Mutation in gene regulating cell growth increases mitosis
- hormones/growth factors
- receptors (that they interact with)
- cell signaling molecules
- transcription factors
what is tumour suppressor?
Tumour suppressor (loss of function)
Mutation in gene that normally suppresses mitosis and cell growth or induces apoptosis (job is normally to prevent damaged cells to replicate)
- transcription factors/repressors
- regulate cell cycle, apoptosis or DNA repair
what is angiogenesis?
Angiogenesis
- Larger tumours require oxygen and nutrients (cancer cells need blood and oxygen)
- Tumours secrete growth factors to induce blood vessel growth.
what is metastasis?
Metastasis: leave primary tumour and embed in a new location (least understood and most feared aspect of cancer)
- Detachment of cells from parent tumour
- Entry into lymphatic/blood vessel
- Exit circulation
- Survival and proliferation in new environment
what are the treatment principles?
Tumour
- primary or localized metastatic
Treatment
- surgery / radiation chemotherapy
- Chemotherapy can be used in addition to radiation/surgery
Before: to shrink tumour
After: to kill any remaining cancer cells
- Chemotherapeutic agents are used to cure cancer or for palliative care
- Most anticancer drugs interfere with DNA
therefore, more effective at killing rapidly dividing cells
what are the components of the cell cycle?
Cell cycle
Knowledge of cell cycle and tumour growth kinetics important for:
- design of effective treatments
- understanding lack of drug response
- many drugs most cytotoxic during S-phase
- some effective during M- phase
- most drugs ineffective in G0 phase
how does growth rate contribute to chemo?
Growth fraction = % dividing cells sensitive to chemotherapy (high percentage cells vulnerable)
- Majority of cells in young tumours actively dividing.
As the tumour grows, percentage-wise, not as many cells are actively dividing; it may be more aggressive, metastasize, or not respond well to chemotherapy.
* Debulking tumours stimulates proliferation
* Early metastases have high growth fraction
* Fast-growing cancers more responsive
* Several treatment cycles necessary to synchronize cells
what is the log kill concept?
- log kill concept focuses on the proportion of cells
- Chemotherapy kills cancer cells via first-order kinetics (constant %)
- At time of detection more than 1 billion cancer cells
- If 99.99% of cells (10^9) killed (9.999 X 10^8), 0.01 % of cells remain (10^5 cells)
10^9 to 10^5 = 4 log kill - Cancer growth can occur as tissues recover between treatments
