Introduction to Chemotherapy
- cancer affects 1 in every 3 individuals
- Cancer incidence and mortality
Ø Males – lung #1, prostate #2
Ø Females – lung #1, breast #2
- Causes of cancer
Ø most are non-inherited genetic diseases of somatic cells
Ø mutations can occur spontaneously or can be induced or increased by exposure to mutagenic substances in the environment
Ø Tobacco – single leading cause of cancer mortality – 1/3 of all cancer related deaths
Ø Dietary factors
Ø Environmental exposure
- Etiology of Cancer
Ø multistep process requiring the mutation or inappropriate expression of several genes
- Common Features shared by tumors
1) hypersensitivity to growth signals
2) insensitivity to anti-growth signals
3) ability to evade apoptosis
4) limitless replicative potentail
5) sustained angiogenesis
6) tissue invasion and metastasis
- Treatment of Cancer – surgery, radiation, chemo
- Hx of Chemotherapy
Ø 1865 – Fowler’s solution (Potassium arsenite) used to treat leukemia
Ø Nitrogen mustard in the mid 1940s
- Principles of Chemotherapy
Ø Total Cell Kill Hypothesis
- the goal of chemotherapy is to kill every tumor cell because cancer can potentially arise from a single malignant cell
Ø Tumor Burden
- the greater the tumor burden, the more difficult it is to treat the disease
- Early detection and treatment is critical
Ø Growth Fraction
- only a fraction of the cells in a tumor are dividing at time of chemo
- it is the cells undergoing active growth that are sensitive to the effects of chemotherapy
v the larger the tumor, the smaller the growth fraction
v surgery or radiotherapy can “recruit” cells into the growth fraction (enhances chemotherapy)
Ø Log Cell Kill Concept
- a constant fraction rather than a constant number of cells are killed with each cycle of chemotherapy
- difficult to establish “end-point” of therapy
- aggressive treatment must be continued past “remission”
Ø Narrow Therapeutic Index
- very narrow for most drugs
Ø Effect of Cell Cycle
- G2, M, S, non-specific phases of cell cycle are targeted by chemotherapeutic agents
Ø Dose limiting Toxicity
- most normal cells have a low growth fraction and are not killed by chemotherapy
- Except: bone marrow stem cells, mucosa, hair follicles
- Damage to normal tissues limits the effectiveness of chemotherapy
- Chemotherapy frequently fails
Ø Drug resistant cells can emerge
- resistance increases as the tumor size increases
- use combo chemotherapy
- occurs spontaneously and randomly
Ø Cells may metastasize to locations that are not reached by the drugs
Tags: Causes of cancer, chemotherapeutic agents, genetic diseases of somatic cells, Principles of Chemotherapy, tumor growth
