1,721,260 research outputs found

    Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer

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    Over the last two decades, many studies have demonstrated that the insulin-like growth factor-1 (IGF-1) is involved in a number of patho-physiological processes, as well as in the development of different types of solid tumors, including breast cancer (BC). Preclinical and clinical data showed that IGF-1 receptor (R) is overexpressed and hyper-phosphorylated in several subtypes of BCs. The central implications of this pathway in tumor cell proliferation and metastasis make it an important therapeutic target. Moreover, the IGF-1 axis has shown strong interconnection with estrogen regulation and endocrine therapy, suggesting a possible solution to anti-estrogen resistance. IGF-1R might also interfere with other pivotal therapeutic strategies, such as anti HER2 treatments and mTOR inhibitors; several clinical trials are ongoing evaluating the role of IGF-1R inhibition in modulating resistance mechanisms to target therapies. Our aim is to offer an overview of the most recent and significant field of application of IGF-1 inhibitors and relevant therapeutic strategies, weighing their possible future impact on clinical practice

    Enzalutamide in prostate cancer after chemotherapy.

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    In the randomized trial reported by Scher et al. (Sept. 27 issue),1 the administration of enzalutamide, an androgen-receptor–signaling inhibitor, was associated with an increased incidence of headache, as compared with placebo, in patients with castration-resistant prostate cancer. Androgens are implicated in the pathogenesis of migraine; thus, it is important to understand whether the headache associated with enzalutamide could be classified as migraine. Moreover, a deeper understanding of the pathophysiology of this side effect is clinically relevant, since a relationship between migraine and the presence of either hot flashes or seizures has been described previously.2,3 Migraine and epilepsy have pathophysiological characteristics in common,3 so patients who have migraine during enzalutamide therapy may be at increased risk for seizures. Notably, headache was not reported as a clinically relevant symptom in patients with castration- resistant prostate cancer who received abiraterone, 4 a drug that deeply reduces circulating androgen levels. Abiraterone was administered in association with prednisone, and glucocorticoids are efficacious in preventing migraine.5 It would be interesting to know whether glucocorticoids were used in the management of enzalutamide- induced headache and whether they were effective
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