Can antibody-drug conjugates bypass multidrug resistance of cancer cells?

Drug resistance in cancer cells remains a significant hurdle
to successful chemotherapy of cancer patients. Despite
the development of new drugs designed to interfere with
the unique biology of cancer cells, the common outcome
of chemotherapy is the outgrowth of malignant clones
resistant to drug action. Targeted drug delivery (TDD) systems,
exemplified by antibody–drug conjugates (ADC),
deliver their payloads through a pathway that should
bypass drug resistance mechanisms. In this chapter we
review the evidence for this possibility and find that ADCs
can bypass drug resistance and kill tumor cells. ADC efficacy
depends on the type of targeting antibody used,
conjugation chemistry and the chemical nature of the
drug. With these considerations in place, the near future
should see the development of evenmore clinically effective
ADCs.