anthracycline

How do they work?

Three actions combine. The flat ring system wedges itself between the paired bases of DNA, distorting the ladder. That wedging traps topoisomerase II, an enzyme that cuts both strands to untangle them and then reseals them, so the cuts stay open. The drug also generates reactive oxygen molecules that damage nearby structures. A cell attempting to divide with broken DNA triggers its own death, which is why tissues that turn over quickly, including tumors, marrow, hair follicles and gut lining, are hit hardest.

Which drugs belong to the family?

Why is the heart the limiting factor?

Heart muscle handles oxidative damage poorly and does not replace lost cells. Harm accumulates with every dose ever given, so the risk is tied to the lifetime total rather than to any single infusion, and a total dose ceiling is respected across the whole of a person's treatment history. The weakening can appear during treatment or surface many years later as heart failure. Heart function is imaged before and during a course for this reason. A liposomal form, in which the drug is enclosed in fat bubbles, and a protective agent given alongside are two approaches used to reduce the burden.

What else do they cause?

Anthracyclines are deep red, and the urine turns red or orange for a day or two afterward, which is harmless and often alarming. They damage tissue severely if they leak out of the vein, they suppress the marrow, and hair loss is usual. Nausea is common. They remain in wide use because few drug classes match their effect on the cancers listed above. A second, rarer concern is that the same DNA damage which kills tumor cells can occasionally injure a surviving marrow cell in a way that leads years later to a new blood cancer. That risk is small set against the benefit in the diseases these drugs treat, but it is one reason total exposure is kept to what is needed.