TY - JOUR
T1 - A way forward for cancer chemoprevention
T2 - Think local
AU - Rabadi, Luai Al
AU - Bergan, Raymond
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - As cells progress through carcinogenesis, the associated exponential expansion of genetic and molecular aberrations and resultant heterogeneity make therapeutic success increasingly unattainable. Therapeutic intervention at early stages of carcinogenesis that occurs within the primary organ and in the face of a lower burden of molecular aberrations, constitutes a basic tenet of cancer chemoprevention, and provides a situation that favors a greater degree of therapeutic efficacy compared with that of advanced cancer. A longstanding barrier to chemoprevention relates to the requirement for essentially no systemic toxicity, and the fact that when large numbers of people are treated, the emergence of systemic toxicity is almost universal. A rational means to address this in fact relates to a second basic tenet of the chemopreventive strategy: the focus of therapeutic intervention is to disrupt a process that is in essence localized to a single organ. Based upon this consideration, a strategy which is based upon local delivery of therapeutics to an at-risk organ will achieve therapeutic efficacy while avoiding systemic delivery and its associated toxicity. This article will review the rationale for undertaking such an approach, describe successful clinical achievements based on this strategy, describe ongoing efforts to expand the impact of this approach, and together will highlight the high impact that this approach has already had on the field as well as its extremely high potential for future impact.
AB - As cells progress through carcinogenesis, the associated exponential expansion of genetic and molecular aberrations and resultant heterogeneity make therapeutic success increasingly unattainable. Therapeutic intervention at early stages of carcinogenesis that occurs within the primary organ and in the face of a lower burden of molecular aberrations, constitutes a basic tenet of cancer chemoprevention, and provides a situation that favors a greater degree of therapeutic efficacy compared with that of advanced cancer. A longstanding barrier to chemoprevention relates to the requirement for essentially no systemic toxicity, and the fact that when large numbers of people are treated, the emergence of systemic toxicity is almost universal. A rational means to address this in fact relates to a second basic tenet of the chemopreventive strategy: the focus of therapeutic intervention is to disrupt a process that is in essence localized to a single organ. Based upon this consideration, a strategy which is based upon local delivery of therapeutics to an at-risk organ will achieve therapeutic efficacy while avoiding systemic delivery and its associated toxicity. This article will review the rationale for undertaking such an approach, describe successful clinical achievements based on this strategy, describe ongoing efforts to expand the impact of this approach, and together will highlight the high impact that this approach has already had on the field as well as its extremely high potential for future impact.
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U2 - 10.1158/1940-6207.CAPR-16-0194
DO - 10.1158/1940-6207.CAPR-16-0194
M3 - Review article
C2 - 27780807
AN - SCOPUS:85009193723
SN - 1940-6207
VL - 10
SP - 14
EP - 35
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 1
ER -