Intercepting neoplastic progression in lung malignancies via the beta adrenergic (β-AR) pathway: implications for anti-cancer drug targets.

Abstract:

:The understanding of signaling cascades involved in the induction, promotion, and progression of cancer, although advanced in recent years, is still incomplete. Tracing the imbalance of the impaired, physiologically-essential cellular signaling that drives the neoplastic process is a complex issue. This review discusses the role of the regulator of the fight or flight response, the beta-adrenergic signaling cascade, as a mediator of cancer growth and progression in in vitro and in vivo cancer models. We review a series of experiments from our own laboratory and those of others examining the contribution of this signaling network to lung and other human malignancies and thereby identifying potential targets for chemotherapeutic interventions. The stimulation of the β-adrenergic receptor by lifestyle and environmental factors, as well as a preexisting risk for neoplasm, activates downstream effector molecules (adenylyl cyclase/cAMP/PKA/CREB) concomitant to the transactivation of related pathways (EGFR) that lead to pro-oncogenic signaling; this β-adrenergic pathway thereby encourages cancer growth by evasion of apoptosis, invasion, angiogenesis, and metastasis. GABAergic signaling acts as an antagonist to the β-adrenergic cascade by intercepting adenylyl cyclase activation, and thereby neutralizing the pro-oncogenic effects of β-adrenergic stimulation. The regulation of cancer cell growth by neurobiological signals expands the possibilities for pharmacological interventions in cancer therapy.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Al-Wadei HA,Ullah MF,Al-Wadei MH

doi

10.1016/j.phrs.2012.03.014

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

33-40

issue

1

eissn

1043-6618

issn

1096-1186

pii

S1043-6618(12)00057-6

journal_volume

66

pub_type

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