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Tumor lymphangiogenesis as a potential therapeutic target.

ABSTRACT: Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis.

SUBMITTER: Duong T

PROVIDER: S-EPMC3307004 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Tumor lymphangiogenesis as a potential therapeutic target.

Duong Tam T Koopman Peter P Francois Mathias M

Journal of oncology 20120216

Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) ...[more]

PMID: 22481918

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Project description:Tumor-related activities that seem to be operationally induced by the division of function, such as inflammation, neoangiogenesis, Warburg effect, immune response, extracellular matrix remodeling, cell proliferation rate, apoptosis, coagulation effects, present itself from a systems perspective as an enhancement of complexity. We hypothesized, that tumor systems-directed therapies might have the capability to use aggregated action effects, as adjustable sizes to therapeutically modulate the tumor systems' stability, homeostasis, and robustness. We performed a retrospective analysis of recently published data on 224 patients with advanced and heavily pre-treated (10% to 63%) vascular sarcoma, melanoma, renal clear cell, cholangiocellular, carcinoma, hormone-refractory prostate cancer, and multivisceral Langerhans' cell histiocytosis enrolled in nine multi-center phase II trials (11 centers). Each patient received a multi-targeted systems-directed therapy that consisted of metronomic low-dose chemotherapy, a COX-2 inhibitor, combined with one or two transcription modulators, pioglitazone +/- dexamethasone or IFN-alpha. These treatment schedules may attenuate the metastatic potential, tumor-associated inflammation, may exert site-specific activities, and induce long-term disease stabilization followed by prolonged objective response (3% to 48%) despite poor monoactivity of the respective drugs. Progression-free survival data are comparable with those of reductionist-designed standard first-line therapies. The differential response patterns indicate the therapies' systems biological activity. Understanding systems biology as adjustable size may break through the barrier of complex tumor-stroma-interactions in a therapeutically relevant way: Comparatively high efficacy at moderate toxicity. Structured systems-directed therapies in metastatic cancer may get a source for detecting the topology of tumor-associated complex aggregated action effects as adjustable sizes available for targeted biomodulatory therapies.

Dataset Information

Tumor lymphangiogenesis as a potential therapeutic target.

Publications

Tumor lymphangiogenesis as a potential therapeutic target.

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