Targeting stroma to treat cancers

• Published in: Seminars in cancer biology Vol. 22; no. 1; pp. 41 - 49
• Main Authors: Engels, Boris, Rowley, Donald A, Schreiber, Hans
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2012
• Subjects: Cancer therapy; Disease Progression; Eradication; Hematology, Oncology and Palliative Medicine; Humans; Neoplasms - physiopathology; Neoplasms - therapy; Paracrine Communication - physiology; Relapse; Stromal Cells - physiology; Tumor promotion; Tumor stroma; TAM; TCR; Relapse; MDSC; tumor-associated fibroblast; matrix metalloproteinase-9; phorbol 12-myristate 13-acetate; Tumor stroma; MHC; tumor-associated macrophage; BM; major histocompatibility complex; Eradication; myeloid-derived suppressor cell; HSC; fibroblast activation protein-α; Tumor promotion; T cell receptor; PMA; VEGF; T reg; regulatory T cell; bone marrow; ECM; APC; FAP; vascular endothelial growth factor; Cancer therapy; TAF; antigen presenting cell; hematopoietic stem cells; MMP-9; dendritic cell; extracellular matrix; DC; Treg
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2011.12.008

Abstract All cancers depend on stroma for support of growth. Leukemias, solid tumors, cancer cells causing effusions, metastases as well as micro-disseminated cancer cells release factors that stimulate stromal cells, which in turn produce ligands that stimulate cancer cells. Therefore, elimination of stromal support by destroying the stromal cells or by inhibiting feedback stimulation of cancer growth is in the focus of many evolving therapies. A stringent evaluation of the efficacy of stromal targeting requires testing in animal models. Most current studies emphasize the successes of stromal targeting rather than deciphering its limitations. Here we show that many of the stromal targeting approaches, while often reducing tumor growth rates, are rarely curative. Therefore, we will also discuss conditions where stromal targeting can eradicate large established tumors. Finally, we will examine still unanswered questions of this promising and exciting area of cancer research.