Targeting Toxins toward Tumors

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Many cancer diseases, e.g., prostate cancer and lung cancer, develop very slowly. Common
chemotherapeutics like vincristine, vinblastine and taxol target cancer cells in their proliferating states.
In slowly developing cancer diseases only a minor part of the malignant cells will be in a proliferative
state, and consequently these drugs will exert a concomitant damage on rapidly proliferating benign
tissue as well. A number of toxins possess an ability to kill cells in all states independently of whether
they are benign or malignant. Such toxins can only be used as chemotherapeutics if they can be
targeted selectively against the tumors. Examples of such toxins are mertansine, calicheamicins and
thapsigargins, which all kill cells at low micromolar or nanomolar concentrations. Advanced prodrug
concepts enabling targeting of these toxins to cancer tissue comprise antibody-directed enzyme
prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), lectin-directed enzymeactivated prodrug therapy (LEAPT), and antibody-drug conjugated therapy (ADC), which will be
discussed in the present review. The review also includes recent examples of protease-targeting
chimera (PROTAC) for knockdown of receptors essential for development of tumors. In addition,
targeting of toxins relying on tumor-overexpressed enzymes with unique substrate specificity will
be mentioned.
Original languageEnglish
Article number1292
Issue number5
Number of pages23
Publication statusPublished - 2021

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