Module 17- Cancer Chemotherapy Flashcards
Characteristics of Cancer Cells
1) Persistent uncontrollable cell proliferation
2) Invasive – cancer cells invade adjacent tissue, facilitating cancer growth in different areas of the body.
3) Metastatic – the ability of cancer cells to travel to different sites in the body and invade to form new tumours.
4) Immortal – Cancer cells do not die, they continually divide.
5) Angiogenesis – Cancer cells develop their own blood vessels to supply nutrients. This is a critical step to allow them to proliferate.
Treatment Modalities for Cancer
1) Surgery – the tumour is removed.
2) Radiation – high energy radiation is used to shrink tumours and kill cancer cells. Radiation therapy damages DNA of both cancerous and non-cancerous cells.
3) Chemotherapy – Drugs are used to treat cancer. As cancerous cells are dividing rapidly, chemotherapeutic drugs target rapidly dividing cells.
G0 - Cell Cycle
resting, no replication
G1 - Cell cycle
the cell prepares to synthesize its DNA (duplicate)
S- Cell cycle
cell synthesizes DNA
G2 - cell cycle
cell preps for mitosis
M - cell cycle
cell divides in mitosis
Toxicity to Normal Cells
Neoplastic cells (i.e. cancer cells) are very similar to normal cells. Therefore it is difficult to specifically target only cancer cells during chemotherapy
The most cellular toxicity occurs to cells with a high growth fraction. The growth fraction is the ratio of proliferating cells to cells in the resting (G0) state. Examples of cells with a high growth fraction include: bone marrow, GI epithelium, hair follicles and the germinal epithelium of the testes, that gives rise to sperm.
Aside from killing cancer cells, chemotherapeutic drugs kill normal cells.
Cure of Cancer Requires 100% Cell Kill
In order to cure cancer, we must kill virtually all cancerous cells in the body. This is difficult as there are not good tests to determine whether cancerous cells are present in the body in low numbers.
The kinetics of cell death with chemotherapy are first-order. This means that a constant percentage of cancerous cells are killed at a given dose of drug.
Breast Cancer Detection
Clinical Breast Examination every 2-3 years for women over 50. High risk patients should be screened more often and screening may start earlier than age 50.
Cervical Cancer detection
The most important risk factor for cervical cancer is Human Papillomavirus (HPV) infection. HPV is spread primarily by genital skin-to-skin contact and it is estimated that over 75% of women AND men will have at least one HPV infection in their lifetime. Sexually active women should have a Pap test every 1-3 years.
Colorectal Cancer detection
Men and women over 50 who are not at high risk should have a fecal occult blood test every two years.
Colonoscopy may also be performed every 5 years in high risk patients.
Prostate detection cancer
Men over 50 should have the Digital Rectal Exam and/or the Prostate Specific Antigen blood test.
Prostate detection cancer
Men over 50 should have the Digital Rectal Exam and/or the Prostate Specific Antigen blood test.
Skin cancer detection
Self-checks should be performed regularly. In particular, look for changes to birthmarks and/or moles, any new skin growths, and sores that don’t heal properly.
Testicular Cancer detection
Males over the age of 15 should regularly perform the Testicular Self Examination.
Solid Tumours Respond Poorly To Chemotherapy
Solid tumours have a large fraction of cells in the resting (G0) state. As most chemotherapeutic drugs target proliferating cells, solid tumours don’t respond as well.
Drug Resistance
Mechanisms of resistance can include:
- decreased drug uptake,
- increased drug efflux,
- decreased drug activation (in the case of prodrugs),
- reduced target sensitivity, increased cellular (primarily DNA) repair.
- Decreased apoptosis (programmed cell death).
P-glycoprotein is an efflux drug pump that pumps drugs out of cells (remember Module 2?). By not allowing cellular accumulation of chemotherapeutic drugs, P-glycoprotein can cause multiple drug resistance.
Resistant cells are not killed by chemotherapeutic agents and therefore this phenomenon can cause therapeutic failure.
Intermittent Chemotherapy
The intent of this strategy is to kill cancer cells by administering chemotherapeutic drugs intermittently. This allows time for normal cells to recover.
For this approach to be successful, normal cells must grow back faster than cancerous cells as in the example on the right.