PPARs: A Double-Edged Sword in Cancer Therapy?

Call for Papers

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors with pleiotropic cellular effects. Because of their antiproliferative, proapoptotic, and differentiation promoting activities, as well as their pharmacological accessibility, the family of PPARs has attracted interest as targets for anticancer therapy. However, ligand activation of PPARs or their genetic abrogation may, depending on the context, either promote or suppress cancer. Thus, PPAR agonists and/or antagonists are potentially double-edged swords for cancer therapy. Meanwhile, a new picture of tumors has emerged in which noncancerous cells of the tumor stroma contribute to tumor growth. The processes involved, angiogenesis and inflammation, are also regulated by PPARs. Thus, PPARs control cell-autonomous as well as non-cell-autonomous processes in cancer. This heterogeneity of cellular targets combined with their biphasic dose effects on both pro- and antitumor processes may account for the apparent paradoxical effects of PPAR agonists on tumor growth.

Clinical trials of PPAR agonists have not shown dramatic antitumor effects when used as single-drug therapy. However, in recent experimental studies they show synergistic activity with other antitumor drugs. One complicating factor is that PPAR agonists may also act through PPAR‒independent pathways, raising the question as to which effects are off-target (not PPAR-mediated)? A special issue of PPAR Research dedicated to PPARs and cancer will hopefully shed light onto the broadening front of research onto this multifaceted problem.

We invite authors to present original research articles, reviews, or minireviews that will stimulate the continuing efforts in understanding PPAR's role in cancer, specifically, the anti- or protumorigenic role of PPARs. Studies that evaluate the cellular and molecular mechanisms linking PPARs to cancer, or the clinical benefits of PPAR ligands, in cancer treatment are also welcomed. Reviews that survey the complex and contradictory effects of the PPARs and their agonists will be of great utility to the growing community of PPAR and cancer researchers.

Potential topics include but are not limited to:

  • PPARs and cancer
  • PPARs role in differentiation, cell-cycle, apoptosis, angiogenesis, and inflammation
  • Combination therapy of PPAR agonists with other antitumor agents

Authors should follow the PPAR Research manuscript format described at the journal site http://www.hindawi.com/journals/ppar/. Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at http://mts.hindawi.com/, according to the following timetable:

Manuscript DueMarch 1, 2008
First Round of ReviewsJune 1, 2008
Publication DateSeptember 1, 2008

Guest Editors

  • Dipak Panigrahy, Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
  • Arja Kaipainen, Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
  • Mark Kieran, Deptartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
  • Judah Folkman, Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
  • Sui Huang, Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA; University of Calgary, Alberta, Canada T2N 1N4