Targeting Toxins toward Tumors
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Targeting Toxins toward Tumors. / Franzyk, Henrik; Christensen, Søren Brøgger.
I: Molecules, Bind 26, Nr. 5, 1292, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Targeting Toxins toward Tumors
AU - Franzyk, Henrik
AU - Christensen, Søren Brøgger
PY - 2021
Y1 - 2021
N2 - Many cancer diseases, e.g., prostate cancer and lung cancer, develop very slowly. Commonchemotherapeutics 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 proliferativestate, and consequently these drugs will exert a concomitant damage on rapidly proliferating benigntissue as well. A number of toxins possess an ability to kill cells in all states independently of whetherthey are benign or malignant. Such toxins can only be used as chemotherapeutics if they can betargeted selectively against the tumors. Examples of such toxins are mertansine, calicheamicins andthapsigargins, which all kill cells at low micromolar or nanomolar concentrations. Advanced prodrugconcepts enabling targeting of these toxins to cancer tissue comprise antibody-directed enzymeprodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), lectin-directed enzymeactivated prodrug therapy (LEAPT), and antibody-drug conjugated therapy (ADC), which will bediscussed in the present review. The review also includes recent examples of protease-targetingchimera (PROTAC) for knockdown of receptors essential for development of tumors. In addition,targeting of toxins relying on tumor-overexpressed enzymes with unique substrate specificity willbe mentioned.
AB - Many cancer diseases, e.g., prostate cancer and lung cancer, develop very slowly. Commonchemotherapeutics 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 proliferativestate, and consequently these drugs will exert a concomitant damage on rapidly proliferating benigntissue as well. A number of toxins possess an ability to kill cells in all states independently of whetherthey are benign or malignant. Such toxins can only be used as chemotherapeutics if they can betargeted selectively against the tumors. Examples of such toxins are mertansine, calicheamicins andthapsigargins, which all kill cells at low micromolar or nanomolar concentrations. Advanced prodrugconcepts enabling targeting of these toxins to cancer tissue comprise antibody-directed enzymeprodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), lectin-directed enzymeactivated prodrug therapy (LEAPT), and antibody-drug conjugated therapy (ADC), which will bediscussed in the present review. The review also includes recent examples of protease-targetingchimera (PROTAC) for knockdown of receptors essential for development of tumors. In addition,targeting of toxins relying on tumor-overexpressed enzymes with unique substrate specificity willbe mentioned.
KW - Faculty of Health and Medical Sciences
KW - Prodrugs
KW - Medicinal chemistry
KW - Chemotherapy
KW - Natural products
KW - review article
U2 - 10.3390/molecules26051292
DO - 10.3390/molecules26051292
M3 - Journal article
C2 - 33673582
VL - 26
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 5
M1 - 1292
ER -
ID: 257415333