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Therapeutic Implications of TGF? in Cancer Treatment: A Systematic Review.

ABSTRACT: Transforming growth factor ? (TGF?) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of this factor, or the deregulation of its signaling cascade, can lead to different pathologies, including cancer. A great variety of therapeutic strategies targeting TGF?, or the members included in its signaling pathway, are currently being researched in cancer treatment. However, the dual role of TGF?, as a tumor suppressor or a tumor-promoter, together with its crosstalk with other signaling pathways, has hampered the development of safe and effective treatments aimed at halting the cancer progression. This systematic literature review aims to provide insight into the different approaches available to regulate TGF? and/or the molecules involved in its synthesis, activation, or signaling, as a cancer treatment. The therapeutic strategies most commonly investigated include antisense oligonucleotides, which prevent TGF? synthesis, to molecules that block the interaction between TGF? and its signaling receptors, together with inhibitors of the TGF? signaling cascade-effectors. The effectiveness and possible complications of the different potential therapies available are also discussed.

SUBMITTER: Gomez-Gil V

PROVIDER: S-EPMC7864190 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review.

Gómez-Gil Verónica V

Cancers 20210120 3

Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of this factor, or the deregulation of its signaling cascade, can lead to different pathologies, including cancer. A great variety of therapeutic strategies targeting TGFβ, or the members included in its signaling pathway, are currently being researched in cancer treatment. However, the dual role of TGFβ, as a tumor suppressor or a tumo ...[more]

PMID: 33498521

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Project description:Background: Antipsychotic-induced weight gain (AIWG) and other adverse metabolic effects represent serious side effects faced by many patients with psychosis that can lead to numerous comorbidities and which reduce the lifespan. While the pathophysiology of AIWG remains poorly understood, numerous studies have reported a positive association between AIWG and the therapeutic benefit of antipsychotic medications. Objectives: To review the literature to (1) determine if AIWG is consistently associated with therapeutic benefit and (2) investigate which variables may mediate such an association. Data Sources: MEDLINE, Google Scholar, Cochrane Database and PsycINFO databases were searched for articles containing all the following exploded MESH terms: schizophrenia [AND] antipsychotic agents/neuroleptics [AND] (weight gain [OR] lipids [OR] insulin [OR] leptin) [AND] treatment outcome. Results were limited to full-text, English journal articles. Results: Our literature search uncovered 31 independent studies which investigated an AIWG-therapeutic benefit association with a total of 6063 enrolled individuals diagnosed with schizophrenia or another serious mental illness receiving antipsychotic medications. Twenty-two studies found a positive association while, 10 studies found no association and one study reported a negative association. Study variables including medication compliance, sex, ethnicity, or prior antipsychotic exposure did not appear to consistently affect the AIWG-therapeutic benefit relationship. In contrast, there was some evidence that controlling for baseline BMI/psychopathology, duration of treatment and specific agent studied [i.e., olanzapine (OLZ) or clozapine (CLZ)] strengthened the relationship between AIWG and therapeutic benefit. Limitations: There were limitations of the reviewed studies in that many had small sample sizes, and/or were retrospective. The heterogeneity of the studies also made comparisons difficult and publication bias was not controlled for. Conclusions: An AIWG-therapeutic benefit association may exist and is most likely to be observed in OLZ and CLZ-treated patients. The clinical meaningfulness of this association remains unclear and weight gain and other metabolic comorbidities should be identified and treated to the same targets as the general population. Further research should continue to explore the links between therapeutic benefit and metabolic health with emphasis on both pre-clinical work and well-designed prospective clinical trials examining metabolic parameters associated, but also occurring independently to AIWG.

Dataset Information

Therapeutic Implications of TGF? in Cancer Treatment: A Systematic Review.

Publications

Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review.

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