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Oncogenic resistance to growth-limiting conditions

Nature Reviews Cancer volume 2, pages 221–224 (2002)Cite this article

Abstract

Many carcinogens are mutagens, indicating that mutagenesis is the driving force of carcinogenesis. But what if we turn this prevailing view on its head? I will argue here that carcinogens are cytostatic and/or cytotoxic, and it is not mutation per se, but clonal selection for resistance to these antiproliferative conditions, that leads to cancer. But why aren't all cytotoxins carcinogenic?

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Figure 1: Cancer as a by-product of adaptation to the environment.
Figure 2: Two types of mechanism of resistance: non-oncogenic or oncogenic.
Figure 3: Development of non-oncogenic or oncogenic resistance to an antimicrotubule agent, Taxol.
Figure 4: A single alteration in a signalling pathway can change the output from growth inhibition to growth stimulation.
Figure 5: Continuous process of carcinogenesis: from cancer initiation to cancer therapy.

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Author information

Authors and Affiliations

  1. the Department of Medicine, New York Medical College, Brander Cancer Research Institute, New York, 10532, Hawthorne, USA

    Mikhail V. Blagosklonny

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  1. Mikhail V. Blagosklonny
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DATABASES

CancerNet:

acute myeloid leukaemia

chronic myelogenous leukaemia

hepatomas

prostate cancer

skin tumours

testicular cancer

 LocusLink:

ABL

AKT

BCL2

BCL-XL

BCR

cyclin D1

E2F

v-Fos

v-Hras

hypoxia-inducible factor

INK4A

INK4B

MAPK

metallothionein

c-MYC

p53

RB

SRC

Tgf-α

TGF-β

tubulin

WAF1

 Medscape DrugInfo:

5-fluorouracil

Glivec

paclitaxel

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Blagosklonny, M. Oncogenic resistance to growth-limiting conditions. Nat Rev Cancer 2, 221–224 (2002). https://doi.org/10.1038/nrc743

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