The Grand Challenges to Cellular and Molecular Oncology

In the last decade, our molecular and cellular understanding of cancer has been tremendously ameliorated. It has been demonstrated that, in some cellular settings, microRNAs (miRNAs) can exert bona fide oncogenic or oncosuppressive functions (Croce, 2009) and that cancer cells often, if not always, exhibit an extensive metabolic rewiring (Kroemer and Pouyssegur, 2008); the compartment of cancer stem cells has been intensely studied (Visvader and Lindeman, 2008); the concepts of oncogene/non-oncogene addiction (Luo et al., 2009) and of immunogenic cell death (Zitvogel et al., 2010) have been founded; and novel modalities of programmed cell death have been characterized (Vandenabeele et al., 2010), just to mention a few examples. These advances in our fundament knowledge of molecular and cellular cancer biology are rapidly being translated into ever more reliable diagnostic and prognostic biomarkers as well as into a large armamentarium of novel therapeutic tools. Personalized anticancer strategies, which at the end of the 1990s held great expectations, have now turned into a clinically exploitable reality. Moreover, there is now an emerging tendency to conceive tumors as micro-ecosystems that are composed by a heterogeneous population of cancer (stem) cells as well as a plethora of distinct stromal cells, including fibroblasts and endothelial cells, which either promote or limit tumor growth at the metabolic, architectonic, trophic, and immunological levels.

New knowledge generates new questions, and there also remain several old unresolved issues. For instance, do cancer stem cells occupy a physical niche within solid tumors of do they represent a functional compartment only? How can we exploit cancer stem cell biology to increase their sensitivity to therapy? How can we induce the immunogenic demise of tumor cells and hence circumvent their resistance to conventional anticancer regimens? What components of the molecular machinery for necroptosis might be exploited for the generation of novel cytotoxic agents that do not operate via apoptosis? How can we target the tumor-stroma for developing safe and efficient anticancer strategies? Will nanoparticles and other molecular targeting devices progress until clinical applications? These are only some of the great questions that will drive the work of us, as cellular and molecular oncologists, for the next few years. We must concentrate our efforts to reach an ever more precise characterization of the mechanisms that underlie the origin, survival, and therapeutic response of cancer. It can be anticipated that this will lead to the development of new, efficient approaches for the treatment of this dreadful disease.

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