Faculté des sciences

Molecular Pathways: Emerging pathways mediating growth, invasion and metastasis of tumors progressing in an irradiated microenvironment

Kuonen, Francois ; Secondini, Chiara ; Ruegg, Curzio

In: Clinical Cancer Research, 2012, p. -

Radiotherapy is a well-established therapeutic modality in oncology. It provides survival benefits in several different cancer types. However, cancers relapsing after radiotherapy often develop into more aggressive conditions, which are difficult to treat and are associated with poor prognosis. Cumulating experimental evidence indicates that the irradiated tumor bed contributes to such aggressive... Plus

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    Summary
    Radiotherapy is a well-established therapeutic modality in oncology. It provides survival benefits in several different cancer types. However, cancers relapsing after radiotherapy often develop into more aggressive conditions, which are difficult to treat and are associated with poor prognosis. Cumulating experimental evidence indicates that the irradiated tumor bed contributes to such aggressive behavior. The involved mechanisms have long remained elusive. Recent progress in the field revealed previously unrecognized cellular and molecular events promoting growth, invasion and metastasis of tumors progressing in an irradiated microenvironment. Cellular mechanisms include inhibition of sprouting angiogenesis, formation of hypoxia, activation and differentiation of stromal cells and recruitment of bone marrow-derived cells with vasculogenic and pro-metastatic activities. Identified pathways include TGFβ/ALK5, CXCL12/CXCR4, KITL/KIT and CYR61/αVβ5 integrin. The availability of pharmacological inhibitors impinging on these pathways opens novel opportunities for translational and clinical studies. These experimental results and ongoing work highlight the importance of the irradiated microenvironment in modulating the tumor response to radiotherapy and open new opportunities for the development of novel therapeutic strategies for cancer patients relapsing after radiotherapy. Here we review and discuss recent advances in the field and their translational and therapeutic implications to human cancer treatment.