Abstract
The term Endocrine Related Cancers classically includes a group of sex steroid responsive cancers, such as cancers of the breast, endometrium, prostate, and testis, but also other cancers such as thyroid and ovary cancers that are responsive to pitui-tary hormones (1). Based on this widely accepted concept, at least 35–40% of newly diagnosed cancers fall into this definition (2). This concept has been useful for its clinical implications, and has lead to the use of anti-estrogenic/anti-androgenic treatments for sex hormone responsive cancers, as well as to thyroid-stimulating hormone (TSH) suppressive therapy with l-thyroxine (-T4) for differentiated thyl -roid cancer. Moreover, several studies have tried to identify physiological conditions, such as early menarche, late menopause, age of first pregnancy, and number of preg-nancies, prolonged lactation, and obesity, that may all affect sex steroids availabil-ity/exposure and modulate cancer risk. Another series of studies have identified germline polymorphisms, which are linked to the modulation of cancer risk through the genetic control of serum hormone lev-els or target tissue responses (3). Finally, other studies have addressed the possi-ble effects of the exposure to exogenous sex hormones, such as estroprogestins (4) or postmenopausal estrogen replac-ing therapy (5) or endocrine disruptors (6). While all these studies have provided useful information for cancer prevention and treatment, our understanding of how genetic traits relevant to hormone action, control and interaction with physiological conditions, hormonal supplementations, and environmental factors is still limited. Another grand challenge is represented by the possibility to achieve effective and risk-free chemoprevention for subjects predisposed to individual endocrine related cancers, as exemplified by the use of tamoxifen and other agents in breast cancer predisposed subjects (6).In recent years, several studies have challenged this classical view of endocrine related cancer. We now summarize recent data, which should be taken into account to reformulate the term “endocrine related cancer” in a more expanded way.
Highlights
In recent years, several studies have challenged this classical view of endocrine related cancer
We summarize recent data, which should be taken into account to reformulate the term “endocrine related cancer” in a more expanded way
Upon cell stimulation by either estrogens or androgens, they form multiprotein complexes at the cell membrane that activate the Src/ ERK/PI3K pathways [7]. This pathway is named MISS and may be upregulated in cancer cells for a number of reasons, among which increased location of sex steroid receptors at the cell membrane and increased expression of adaptor proteins, which favor the formation of multiprotein complexes containing Src [7]
Summary
Several studies have challenged this classical view of endocrine related cancer. In ER-negative and tamoxifen-resistant breast cancer cells, significant cross-talk exists between both EGF and IGF pathways and GPER expression and signaling [10]. Metabolic disorders and cancer: the role of “metabolic hormones” in cancer related tumors Insulin, a new cancer related hormone Overwhelming evidence indicates that both obesity and type 2 diabetes mellitus (T2DM) are associated with up to two to threefold increased risk for various malignancies [15].
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