To Market, to Market—2018: Biologics

Bolger, Catherine A.; Kahn, Suzana A.; Lipovšek, Daša; Mallet, William; Wieler, James G.

doi:10.29200/acsmedchemrev-v54.ch23

Cited by 1 publication

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“…In addition, the progress within the field of ADCs (with an anticancer drug as payload) comprise >60 entities in clinical development [ 62 , 63 , 64 ]. In total eight ADCs have been approved by the FDA as new and improved cancer therapies, albeit not in the period 2014 to 2019 [ 83 , 84 , 85 , 86 , 87 , 88 ]. Calicheamicin and maytansine have been used as the payload in many of these drugs [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting Toxins toward Tumors

Franzyk¹,

Christensen²

2021

Molecules

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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 enzyme-activated 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.

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