GH/IGF e neoplasia: o que há de novo nesta associação

Abstract

RESUMOEstudos in vitro e em animais sugerem que os membros do sistema insulin-like growth factors (IGFs), incluindo IGF-I, IGF-II, receptores de IGF-I e IGF-II (IGF-IR e IGF-IIR), e as IGF-binding proteins (IGFBPs) podem ter um importante envolvimento no desenvolvimento e na progressão de neoplasias. Mais especificamente, as IGFs promovem a progressão do ciclo celular e inibem a apoptose tanto por ação direta com outros fatores de crescimento como por ação indireta interagindo com outros sistemas moleculares intracelulares envolvidos na promoção e/ou progressão do câncer. Além disso, inúmeros estudos epidemiológicos têm sugerido que concentrações elevadas das IGFs, independente das alterações nas IGFBPs, podem estar associadas a um aumento no risco de desenvolver determinadas neoplasias. Esta revisão tem como objetivo apresentar o envolvimento do sistema IGF na regulação tumoral, os principais estudos epidemiológicos realizados e o risco de desenvolvimento de neoplasia em pacientes (com ou sem história pessoal de neoplasia prévia) que receberam hormônio de crescimento (rhGH). É importante salientar que o uso clínico de rhGH, nas indicações aprovadas internacionalmente, é seguro e não existem evidências, até o momento, da associação com o desenvolvimento de neoplasias. Evidence from in vitro and animal studies suggests that members of the insulin-like growth factors (IGFs) system, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the development and progression of cancer. More specifically, IGFs may promote cell cycle progression and inhibition of apoptosis either by directly associating with other growth factors or indirectly by interacting with other molecular systems, which have an established role in carcinogenesis and cancer promotion. In addition, a growing number of epidemiologic studies suggest that increased serum levels of IGFs and/or altered levels of their binding proteins are associated with increased risk for developing several malignancies. This review aims to summarize and to show the role of IGF system in tumor regulation, a revision of epidemiologic studies and the risk of neoplasia in patients (with or without personal history of previous neoplasia) who received growth hormone (rhGH). It is important to emphasize that the clinical use of rhGH, in the indications internationally approved, is secure, and there are not evidences, at this moment, of the association with neoplasias development.

Metabolic Syndrome and Cancer: Cause or Consequence?

“…Thus far, MetS may increase the risk of cancer, whereas, consecutively, cancer may lead to features of MetS [2][3][4][5][6]. The pathophysiological and biological mechanisms underlying the association between MetS and cancer still remain unexplained and are starting to be understood.…”

“…The pathophysiological and biological mechanisms underlying the association between MetS and cancer still remain unexplained and are starting to be understood. Nonetheless, it is apparent by epidemiological studies that MetS traits increase the risk of cancer [5,6] and that, sequentially, survivors of various malignancies may present MetS traits several years after cancer therapy withdrawal [2][3][4].…”

“…Individual requirements of MetS may contribute to the development of various processes leading to cancer, but they all work together beyond that of the individual components alone. The mechanisms involved in carcinogenesis are increased hormone bioavailability, through insulin and insulin-like growth factor (IGF), resulting in IR, enhanced aromatase activity (and increased sex steroids production), elevated adipokine production and glucose utilization, oxidative stress, DNA damage and consequently promoting an energy-rich environment, cell transformation, migration and proliferation, angiogenesis, as well as inhibition of apoptosis [2,[4][5][6]. Insulin receptor, particularly the isoform A, also plays an important role in this process since it is overexpressed in several human malignancies, binding not only insulin, but also IGF-2.…”

“…Additionally, insulin receptors contribute to the formation of hybrid receptors with IGF-1 receptors and, by binding to hybrid receptors, insulin stimulates specific signaling pathways related to IGF-1. Thus far, these receptors are the major targets for novel anti-cancer therapies [2,[4][5][6].…”

“…Overall, the understanding of the complex systems that determine cancer in populations with features of MetS, focusing on anti-cancer and gene therapies, as well as the importance of each individual component of MetS in determining cancer, should be more clearly defined in the near future. Possibly, if we find the best way to prevent MetS in various populations predisposing to metabolic disturbances, we could find the link between these two conditions and prevent cancer development [2][3][4][5][6].…”