A myriad of novel mediators in neoplastic development and progression are currently being explored. Of significance are those that directly explain clinical manifestations of cancer, because understanding these may lead to new diagnostic, preventive, and therapeutic strategies. This review focuses on novel mediators that address how cancer, before it is treated, can induce cachexia, pain, hematological, and immune alterations. It highlights two concepts: first, that a synergy between tumor and stromal cells may be partly responsible for these manifestations, and second, that soluble factors, and in particular cytokines are being identified as major players in tumor-induced local and systemic effects.

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