If bortezomib, a cancer drug, inhibits cell proteasomes, wouldn't resulting protein aggregate in normal cells further increase the risk of cancer?

Question

Bortezomib is an anti-cancer drug that inhibits the proteasomes of cancer cells, allowing proteins that stop cell growth to fold and perform their function.

However, wouldn't bortezomib also affect the proteasomes of normal cells? If the proteasomes of normal cells are inhibited, the major factor in the regulation of unfolded and damaged proteins is gone. The resulting protein aggregate would lead to cell damage and diseases such as cancer, Alzheimer's and Parkinson's.

What is stopping bortezomib from affecting normal cells? Does it?

Answer 1

Proteasome inhibitors do affect normal cells to some extent, but the whole point of using them as cancer treatments is that (some) cancer cells are far more sensitive to proteasome inhibitors than are normal cells. For example, multiple myeloma cells (the first clinical targets of Bortezomib) that overproduce immunoglobulins are dependent on proteasome degradation to eliminate them and are therefore sensitive to Bortezomib. There are many other aspects of cancer cells that may make them more dependent on proteasome; see for instance

Proteasome inhibitors in cancer therapy: Treatment regimen and peripheral neuropathy as a side effect for some examples.

But of course there are effects on normal cells as well, such as the peripheral neuropathy mentioned in that review.