Transforming growth factor-beta: A target for cancer therapy

Kelly, Ronan J.; Morris, John C.

doi:10.3109/15476910903389920

Cited by 36 publications

(33 citation statements)

References 142 publications

(115 reference statements)

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“…TGF-b signaling can be blocked with other approaches, such as translational inhibition by antisense oligonucleotides, small-molecule inhibitors, and peptide aptamers to Samd proteins (Kelly and Morris 2010;Zu and others 2012). GC1008 and 2G7 are 2 other high-affinity monoclonal antibodies to TGF-b that can neutralize all 3 isoforms, but they are associated with certain drawbacks, such as side effects, including generalized inflammation, autoimmune reactions, and tumorigenic risk (Kim and others 2001;Cheng and others 2008;Zu and others 2012).…”

Section: Cytokines and Breast Cancer Treatmentmentioning

confidence: 99%

The Role of Cytokines in Breast Cancer Development and Progression

Esquivel-Velázquez

Ostoa‐Saloma

Palacios-Arreola

et al. 2015

Journal of Interferon & Cytokine Research

421

363

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Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancerrelated disorders.

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Section: Cytokines and Breast Cancer Treatmentmentioning

confidence: 99%

The Role of Cytokines in Breast Cancer Development and Progression

Esquivel-Velázquez

Ostoa‐Saloma

Palacios-Arreola

et al. 2015

Journal of Interferon & Cytokine Research

421

363

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“…For example, the phase I/II trials of AP 12009 reported 2 cases of adverse events that were classified as grade 3, including 1 case of intracranial edema that was associated with treatment of AP 12009 (59). In addition, the phase I study of the panneutralizing anti-TGF-b antibody, GC1008, reported 1 serious event possibly related to treatment, in which a patient with a previous history of skin cancer developed a well-differentiated squamous cell skin carcinoma (47).…”

Section: Limitations Of Anti-tgf-b Therapymentioning

confidence: 99%

“…In clinical trials of the allogenic tumor vaccine Lucanix, adverse events were only reported in 10% of patients but included pain, fatigue, nausea, headaches, cough, and weakness (43). In trials mentioned above with GC1008, adverse events included fatigue, headache, gingival bleeding, and gastrointestinal symptoms, although all adverse events were classified as grade 2 or less (47). On the basis of these data, it is likely that the potential benefit of these treatments will outweigh the possible complications.…”

Section: Limitations Of Anti-tgf-b Therapymentioning

confidence: 99%

Molecular Pathways: Targeting the TGF-β Pathway for Cancer Therapy

Smith

Robin²,

Ford³

2012

Clinical Cancer Research

178

135

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TGF-b is a ubiquitous cytokine that plays an active role in many cellular processes. Nearly every cell type has the ability to secrete TGF-b, as well as the ability to respond to TGF-b via the presence of TGF-b receptors on the cell surface. Consequently, gain or loss of function of the TGF-b pathway and its components are known to lead to a variety of diseases, including cancer. In epithelial cells, TGF-b functions as a tumor suppressor, where it inhibits proliferation, induces apoptosis, and mediates differentiation. Conversely, in other contexts, TGF-b promotes tumor progression through increasing tumor cell invasion and metastasis. Thus, TGF-b can have opposing roles, likely dependent, in part, on whether the cancer is early or late stage. The effects of TGF-b on tumor suppression and promotion are not limited to the tumor cell itself; rather, these effects can also be mediated through the stroma and the immune system. The dichotomous role of TGF-b in cancer highlights our need to understand the contextual effects of this cytokine to better guide patient selection for the use of anti-TGF-b therapies currently in clinical trials.

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“…TGF-β1 (transforming growth factor-beta1) is a multipotent cytokine that plays an important biological effect on tissue and organ development, cellular proliferation, differentiation, survival, apoptosis and fibrosis (Ikushima and Miyazono, 2010;Kelly and Morris, 2010). In the liver, TGF-β1 is hypothesized to serve as an important link between chronic injury, cirrhosis, and HCC (Matsuzaki, 2009).…”

Section: Fen Linmentioning

confidence: 99%