β1-Integrin: A Potential Therapeutic Target in the Battle against Cancer Recurrence

Abstract

Primary cancer treatment, involving both local and often systemic adjuvant therapy, is often successful, especially if the cancer is detected at an early stage of progression. However, for some patients, the cancer may recur either locally or as distant metastases, in some cases many years after apparently successful primary treatment. Significant tumor dormancy has been documented in several cancers, such as breast, melanoma, and renal cancer. Tumor dormancy has long been recognized as an important problem in management of cancer patients. Recent work has clarified biologic aspects of tumor dormancy and has shown that dormant tumor cells may be resistant to cytotoxic chemotherapy and radiation. This work has led to recognition of a key role for b1-integrin in regulating the switch from a dormant state to active proliferation and metastasis. Here we discuss the role of b1-integrin and its signaling partners in regulating the dormant phenotype. We also consider possible therapeutic approaches, such as small molecules or antibodies (ATN-161, volociximab, and JSM6427), directed against b1-integrin signaling to target dormant cancer cells and to prevent metastatic recurrence. Clin Cancer Res; 17(23); 7219-23. Ó2011 AACR.

Epidermal Growth Factor (EGF) Regulates α5β1 Integrin Activation State in Human Cancer Cell Lines through the p90RSK-dependent Phosphorylation of Filamin A

“…Recent studies have provided evidence that activation of ␤1 integrin plays a critical role in the release of metastatic tumor cells from dormancy. Three-dimensional culture systems used to model conditions of tumor dormancy have shown that ligation of ␤1 integrins and subsequent organization of the actin cytoskeleton are required for the conversion of quiescent tumor cells into proliferating cells (32)(33)(34). Identifying the mechanisms by which the integrin activation state regulates metastatic cell growth represents an important avenue of investigation.…”

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

“…These three states of existence represent vastly different cancer biology with significant implications for detection, therapy, and patient outcomes. The factors that control the balance between dormancy and proliferation are poorly understood but are subject of much ongoing research [18][19][20][21].…”

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

“…Malignant cells are constantly changing cell adhesion surface molecules in response to signals in their surroundings, and this will enhance their ability to disseminate locally. For these reasons, targeting the interactions between certain cell adhesion apparatuses and the ECM has been proposed, including cell membrane integrins (61,62). Integrin-related mechanisms have been shown to be essential at different stages of EOC progression.…”