Why cytotoxic chemotherapy damages fast-dividing normal tissues
Cytotoxic chemotherapy (medicines that kill cells, mostly by damaging DNA or blocking cell division) also harms fast-dividing normal tissues, such as bone marrow and hair roots.
Remember
Standard cytotoxic chemotherapy is not specific to cancer: it damages any rapidly dividing tissue, so bone marrow suppression, mucositis (soreness and ulceration of the mouth and gut lining) and hair loss are expected side effects.
Cytotoxic drugs work by interfering with the machinery of cell division, for example by blocking the copying of DNA. Most normal cells divide less often than cancer cells do, so the cancer cells are likelier to be killed. Some healthy tissues renew themselves just as fast, and the drugs do not spare them. The effect is preferential rather than selective: fast-dividing cells are favoured, but normal fast-dividing tissue is harmed too.
The tissues affected most commonly are those with the highest turnover rate, meaning they renew themselves constantly. The bone marrow makes blood cells, and its cells divide continually to replace those that wear out. Damage there is myelosuppression, meaning suppression of the bone marrow. It shows as anaemia, thrombocytopenia (too few platelets) and neutropenia (too few neutrophils, the white cells that fight bacteria). The lining of the mouth and gut is hit as well, and damage to it causes mucositis (soreness and ulceration of the mouth and gut lining). Hair follicles, the small pits in the skin from which hairs grow, are hit too, and damage to them causes alopecia (hair loss).
Hair loss usually starts two to three weeks into treatment and is temporary. With anthracyclines and taxanes (two classes of chemotherapy drug) it is almost universal, but with platinum drugs it is minimal. A cold cap worn during treatment, known as scalp cooling, lowers the chance of it. Neutropenia is the most dangerous, because it can lead to neutropenic sepsis, which is life-threatening and needs antibiotics urgently. Chemotherapy is given with a rest between cycles, since the marrow takes roughly two to three weeks to recover.
Cells in the G0 phase (a quiescent state in which a cell is not preparing to divide) are not killed by most chemotherapy.
Key facts
- Target
- cytotoxic drugs hit cells that are dividing rapidly, whether cancerous or healthy.
- Why neutropenia matters
- it can lead to neutropenic sepsis, a life-threatening infection that needs antibiotics urgently.
- Tissues at risk
- bone marrow, the lining of the mouth and gut, and hair follicles renew themselves constantly, so they are commonly affected.
- Marrow effects
- myelosuppression causes anaemia, neutropenia and thrombocytopenia.
- Hair loss
- alopecia usually starts at 2 to 3 weeks and is temporary, and scalp cooling reduces the chance of it.
- Resting cells
- cells in the G0 phase are not killed by most chemotherapy.
Exam traps
- Cytotoxic drugs do not bind a target specific to the cancer cell, because they have no such specificity: any dividing cell is hit, so bone marrow and other normal tissues are damaged too. A drug that does bind such a target is a targeted therapy.
- Chemotherapy does not preferentially kill resting cells: cells in the G0 phase are not killed by most chemotherapy, and it is the actively dividing hair follicle cells that are harmed.
- Hair loss comes from the same general principle as marrow damage, yet the cells damaged are inside the hair follicle, not inside the bone marrow.
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