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01.12.2014 | Clinical | Ausgabe 4/2014 Open Access

Cancer and Metastasis Reviews 4/2014

Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy

Zeitschrift:
Cancer and Metastasis Reviews > Ausgabe 4/2014
Autoren:
Stefano Fais, Giulietta Venturi, Bob Gatenby
Wichtige Hinweise
An erratum to this article can be found at http://​dx.​doi.​org/​10.​1007/​s10555-014-9534-0.

Abstract

Much effort is currently devoted to developing patient-specific cancer therapy based on molecular characterization of tumors. In particular, this approach seeks to identify driver mutations that can be blocked through small molecular inhibitors. However, this approach is limited by extensive intratumoral genetic heterogeneity, and, not surprisingly, even dramatic initial responses are typically of limited duration as resistant tumor clones rapidly emerge and proliferate. We propose an alternative approach based on observations that while tumor evolution produces genetic divergence, it is also associated with striking phenotypic convergence that loosely correspond to the well-known cancer “hallmarks”. These convergent properties can be described as driver phenotypes and may be more consistently and robustly expressed than genetic targets. To this purpose, it is necessary to identify strategies that are critical for cancer progression and metastases, and it is likely that these driver phenotypes will be closely related to cancer “hallmarks”. It appears that an antiacidic approach, by targetting a driver phenotype in tumors, may be thought as a future strategy against tumors in either preventing the occurrence of cancer or treating tumor patients with multiple aims, including the improvement of efficacy of existing therapies, possibly reducing their systemic side effects, and controlling tumor growth, progression, and metastasis. This may be achieved with existing molecules such as proton pump inhibitors (PPIs) and buffers such as sodium bicarbonate, citrate, or TRIS.

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