TY - JOUR
T1 - Ecological therapy for cancer
T2 - Defining tumors using an ecosystem paradigm suggests new opportunities for novel cancer treatments
AU - Pienta, Kenneth J.
AU - McGregor, Natalie
AU - Axelrod, Robert
AU - Axelrod, David E.
N1 - Funding Information:
Address all correspondence to: Kenneth J. Pienta, MD, 7308 CCC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109. E-mail: [email protected] 1K.J. Pienta is supported by a National Institutes of Health (NIH) grant CA093900, an American Cancer Society Clinical Research Professorship, NIH Specialized Program of Research Excellence (SPORE) in prostate cancer grant P50 CA69568, Cancer Center support grant P30 CA 46592, SouthWest Oncology Group grant CA32102, the Prostate Cancer Foundation, a Ralph Wilson Medical Research Foundation grant, and a Wallace H. Coulter Foundation Translational Partners Seed grant. R. Axelrod is supported by the University of Michigan’s LS&A Enrichment Fund. D.E. Axelrod is supported by NIH grant CA113004. Received 21 August 2008; Revised 16 September 2008; Accepted 18 September 2008 Copyright © 2008 Neoplasia Press, Inc. All rights reserved 1944-7124/08/$25.00 DOI 10.1593/tlo.08178
PY - 2008/11
Y1 - 2008/11
N2 - We propose that there is an opportunity to devise new cancer therapies based on the recognition that tumors have properties of ecological systems. Traditionally, localized treatment has targeted the cancer cells directly by removing them (surgery) or killing them (chemotherapy and radiation). These modes of therapy have not always been effective because many tumors recur after these therapies, either because not all of the cells are killed (local recurrence) or because the cancer cells had already escaped the primary tumor environment (distant recurrence). There has been an increasing recognition that the tumor microenvironment contains host noncancer cells in addition to cancer cells, interacting in a dynamic fashion over time. The cancer cells compete and/or cooperate with nontumor cells, and the cancer cells may compete and/or cooperate with each other. It has been demonstrated that these interactions can alter the genotype and phenotype of the host cells as well as the cancer cells. The interaction of these cancer and host cells to remodel the normal host organ microenvironment may best be conceptualized as an evolving ecosystem. In classic terms, an ecosystem describes the physical and biological components of an environment in relation to each other as a unit. Here, we review some properties of tumor microenvironments and ecological systems and indicate similarities between them. We propose that describing tumors as ecological systems defines new opportunities for novel cancer therapies and use the development of prostate cancer metastases as an example. We refer to this as "ecological therapy" for cancer.
AB - We propose that there is an opportunity to devise new cancer therapies based on the recognition that tumors have properties of ecological systems. Traditionally, localized treatment has targeted the cancer cells directly by removing them (surgery) or killing them (chemotherapy and radiation). These modes of therapy have not always been effective because many tumors recur after these therapies, either because not all of the cells are killed (local recurrence) or because the cancer cells had already escaped the primary tumor environment (distant recurrence). There has been an increasing recognition that the tumor microenvironment contains host noncancer cells in addition to cancer cells, interacting in a dynamic fashion over time. The cancer cells compete and/or cooperate with nontumor cells, and the cancer cells may compete and/or cooperate with each other. It has been demonstrated that these interactions can alter the genotype and phenotype of the host cells as well as the cancer cells. The interaction of these cancer and host cells to remodel the normal host organ microenvironment may best be conceptualized as an evolving ecosystem. In classic terms, an ecosystem describes the physical and biological components of an environment in relation to each other as a unit. Here, we review some properties of tumor microenvironments and ecological systems and indicate similarities between them. We propose that describing tumors as ecological systems defines new opportunities for novel cancer therapies and use the development of prostate cancer metastases as an example. We refer to this as "ecological therapy" for cancer.
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U2 - 10.1593/tlo.08178
DO - 10.1593/tlo.08178
M3 - Article
AN - SCOPUS:70350716805
SN - 1944-7124
VL - 1
SP - 158
EP - 164
JO - Translational Oncology
JF - Translational Oncology
IS - 4
ER -