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Gilbert, AZ, United States

Munoz J.,Banner Anderson Cancer Center | Wheler J.,University of Houston | Kurzrock R.,University of California at San Diego
Cancer and Metastasis Reviews | Year: 2015

Estrogen and progesterone receptors (ERs and PRs) are known for their prognostic as well as treatment predictive value in breast cancer. Although these receptors are differentially expressed in some other malignancies, and likely participate in the biology of those cancer types, the relevance to outcome and therapy is not well established. The use of ER as a highly effective therapeutic target in oncology was pioneered in breast cancer, and the lessons learned from its success could potentially benefit patients with several other malignancies in which hormone receptors are highly expressed. Indeed, there are several potent drugs available that target hormone receptors. These agents show incontrovertible evidence of benefit in patients with hormone receptor-positive breast cancer. It is conceivable that these drugs may have salutary effects in a variety of cancers other than those originating in the breast, based on the overexpression of hormone receptors in some patients, and the preclinical and clinical reports showing responses to these drugs in diverse cancers, albeit in small series or anecdotally. We therefore undertook a literature review in order to summarize the current data regarding the biologic and clinical implications of expression of estrogen and progesterone receptors in various malignancies and the possibilities for deployment of hormone manipulation beyond breast cancer. © 2014, Springer Science+Business Media New York. Source

CarreraSilva E.,Yale University | Chan P.,Yale University | Joannas L.,Yale University | Errasti A.,Yale University | And 13 more authors.
Immunity | Year: 2013

Dendritic cell (DC) activation is essential for the induction of immune defense against pathogens, yet needs to be tightly controlled to avoid chronic inflammation and exaggerated immune responses. Here, we identify a mechanism of immune homeostasis by which adaptive immunity, once triggered, tempers DC activation and prevents overreactiveimmune responses. Tcells, once activated, produced Protein S (Pros1) that signaled through TAM receptor tyrosine kinases in DCs to limit the magnitude of DC activation. Genetic ablation of Pros1 in mouse Tcells led to increased expression of costimulatory molecules and cytokines in DCs and enhanced immune responses to Tcell-dependent antigens, as well as increased colitis. Additionally, PROS1 was expressed in activated human Tcells, and its ability to regulate DC activation was conserved. Our results identify a heretofore unrecognized, homeostatic negative feedback mechanism at the interface of adaptive and innate immunity that maintains the physiological magnitude of the immune response. © 2013 Elsevier Inc. Source

Munoz J.,Banner Anderson Cancer Center | Wheler J.J.,University of Houston | Kurzrock R.,University of California at San Diego
Oncotarget | Year: 2015

Androgen receptors (ARs) play a critical role in the development of prostate cancer. Targeting ARs results in important salutary effects in this malignancy. Despite mounting evidence that ARs also participate in the pathogenesis and/or progression of diverse tumors, exploring the impact of hormonal manipulation of these receptors has not been widely pursued beyond prostate cancer. This review describes patterns of AR expression in a spectrum of cancers, and the potential to exploit this knowledge in the clinical therapeutic setting. Source

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, renal angiomyolipoma and tuberous sclerosis complex, and, in combination with exemestane, for hormone receptor-positive HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. Results from the phase III BOLERO-2 trial demonstrated that everolimus in combination with exemestane provided significant clinical benefit to patients with advanced hormone receptor-positive breast cancer. Although everolimus is generally well tolerated, as with most therapies administered in an advanced cancer setting, drug-related adverse events (AEs) inevitably occur. Most common AEs observed in the everolimus studies include stomatitis, rash, infection, noninfectious pneumonitis, and hyperglycemia. Clinical awareness and early identification of such AEs by oncology nurses are essential to dosing (interruptions, reduction, and treatment discontinuation); quality of life; and, ultimately, patient outcomes. Because everolimus has already been shown to significantly improve clinical efficacy in patients with advanced breast cancer, a proactive approach to the practical management of AEs associated with this mTOR inhibitor as well as other most common AEs observed in this patient population has been reviewed and outlined here. © 2013 The Author(s). Source

Munoz J.,Banner Anderson Cancer Center | Janku F.,University of Houston | Cohen P.R.,University of California at San Diego | Kurzrock R.,University of California at San Diego
Mayo Clinic Proceedings | Year: 2014

Erdheim-Chester disease is a rare CD68+, CD1a- non-Langerhans cell histiocytosis with multiorgan involvement. The etiology of Erdheim-Chester disease is unclear; there are no known associated infectiousor hereditary genetic abnormalities. However, somatic BRAF mutations have recently been identified in these patients. Historically, the literature regarding the management of Erdheim-Chester disease consisted of casereports and small case series with anecdotal therapeutic responses to agents including, but not limited to, cytotoxic chemotherapy, bone marrow transplantation, cladribine, corticosteroids, IFN-α, the BCR-ABL/KIT inhibitor imatinib mesylate, the IL-1 receptor antagonist anakinra, the TNF-inhibitor infliximab, and recently the BRAF inhibitor vemurafenib. We performed a search of the literature using PubMed with the terms Erdheim Chester disease, without date limitations, including case reports, case series, original articles, and previous review articles. In the absence of large-scale studies, experience-based management prevails. The present review details our approach to the management of patients with Erdheim-Chester disease. © 2014 Mayo Foundation for Medical Education and Research. Source

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