Current opinion in oncology
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Exosomes and microvesicles are secreted particles of 30-200 nm in diameter, delimited by a lipid bilayer and containing a wide range of membrane-bound or free proteins and nucleic acids (in particular mRNA and miRNA). Here, we review the properties of tumor-cell-derived microvesicles as carriers of molecular information in relation to cancer progression and promotion of metastasis. ⋯ Because of their stability, exosomes and microvesicles can be retrieved in bodily fluids as biomarkers for cancer detection and monitoring. They offer a range of molecular targets for controlling cell-cell interactions during invasion and metastasis.
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Modern cancer therapies have allowed for a dramatic increase in the survival rates in both children and adults. However, a frequent and unfortunate side-effect of cancer therapy is a long-term decline in neurocognitive function. Specifically, cranial radiation therapy markedly alters memory processes, while chemotherapeutic agents are correlated with deficits in attention, concentration, and speed of information processing. Here, we describe the putative cellular etiologies of cancer treatment-induced cognitive decline, with an emphasis on the role of neural stem and precursor cell dysfunction. ⋯ Further studies are needed to elucidate the role of chemotherapy on cell-intrinsic processes and cellular microenvironments. Further, the effects of the new generation of targeted molecular therapies on neural stem and progenitor cell function remains largely untested. Understanding the mechanisms behind cancer therapy-induced damage to neural stem and precursor cell populations will elucidate neuroprotective and cell replacement strategies aimed at preserving cognition after cancer therapy.
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Recent data from clinical trials evaluating mammalian target of rapamycin (mTOR) inhibitors in the setting of endocrine resistance in luminal (estrogen receptor-positive, human epidermal growth factor receptor 2-negative) breast cancers have validated this pathway as a bona-fide therapeutic target in this setting. There are currently many agents under clinical investigation that inhibit the phosphatidylinositol 3-kinase (PI3K) pathway. We review these findings in the context of the preclinical data and the current status of biomarker development in this field. ⋯ Therapeutic targeting of the PI3K pathway promises improved clinical outcome for patients with luminal breast cancer. Correspondingly, agents that target this pathway are entering the clinic at an unprecedented rate. Future clinical trials that incorporate correlative translational research will help us decipher important information critical for successful development of these agents in breast cancer: which part of the pathway should be targeted and in which clinical scenario; and which patients are more likely to benefit from these drugs, particularly in the adjuvant setting.
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Management of the epithelial ovarian cancer (EOC) remains a therapeutic challenge, with continued poor overall survival (OS). Given low chemotherapy response rates for recurrent disease and short survival times, new treatment options with improved therapeutic indices for targeting cancer's vulnerability are urgently needed in this patient population. ⋯ Ovarian cancer continues to carry the highest mortality among gynecologic cancers in the western world. Clinical development of PARP inhibitors that target DNA repair defects in cancer is a novel and imperative stride in individualized identification of molecular characteristics in management of ovarian cancer.
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The objective of this article is to review the recently published literature on the use of robotic surgery in the management of gynecologic malignancies. ⋯ Current evidence establishes a role for the use of robotic surgery in the treatment of gynecologic malignancies. Further research should be implemented to validate the use of robotic surgery in gynecologic malignancies and to compare its outcomes to those of open and laparoscopic surgery.