temozolomide
Meaning of temozolomide: An oral chemotherapy that reaches brain tissue unaided, which is why it anchors treatment of the most aggressive brain tumors.
Definition of temozolomide
Temozolomide is an alkylating chemotherapy drug, taken as a capsule, used mainly against glioblastoma and other malignant brain tumors. In the bloodstream it converts on its own into an active form that attaches a methyl group to DNA, damaging the strand so the cell can no longer divide. Unlike most chemotherapy drugs, it passes readily into brain tissue.
How does it reach the brain?
A dense wall of tightly joined cells lines the blood vessels of the brain and keeps most drugs out. Temozolomide is small and dissolves in fat, so it slips through without help. That single property is why it is used for brain tumors when more powerful chemotherapy drugs are not: those drugs never arrive in useful amounts. Methods of deliberate blood-brain barrier disruption exist to force other agents across, and temozolomide requires none of them.
How does it damage cancer cells?
The capsule contains an inactive compound. Once absorbed it breaks apart by itself, without needing the liver to process it, into a form that hands a methyl group to DNA. The critical target is one particular position on the base guanine. A methyl group parked there causes the cell to misread the strand while copying it. Repeated failed repair attempts then trigger the cell to destroy itself. Cells that divide rapidly, as tumor cells do, are hit hardest, which is also why normal fast-dividing tissues suffer.
Why does it work better in some tumors?
Cells carry a repair enzyme, MGMT, that plucks the methyl group straight back off and undoes the damage. Whether a tumor makes that enzyme depends on whether the control region of the MGMT gene has been chemically switched off.
| MGMT gene | Repair enzyme | Response to the drug |
|---|---|---|
| Switched off by methylation | Little or none made | Generally better |
| Active | Present and working | Generally poorer |
Testing tumor tissue for this marker is now routine, because it helps predict how much benefit treatment is likely to bring.
What are the main side effects?
Nausea is common and is usually prevented with anti-sickness medicine given beforehand. The effect that matters most is on the bone marrow, where platelet and white cell counts fall, so blood is checked before each cycle. Tiredness, constipation and loss of appetite are frequent. Because the marrow effect accumulates over repeated cycles, the amount given is often adjusted as treatment continues.
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Used in a sentence
The regimen combined radiotherapy with daily temozolomide, followed by further cycles of the drug alone.
Good to know
Temozolomide crosses into brain tissue without assistance, and tumors whose MGMT repair gene has been silenced by methylation generally respond better than those with the gene still active.