Clin Cancer Res
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Genetic alterations that lead to constitutive activation of kinases are frequently observed in cancer. In many cases, the growth and survival of tumor cells rely upon an activated kinase such that inhibition of its activity is an effective anticancer therapy. ⋯ Targeting ROS1 fusion proteins with the small-molecule inhibitor crizotinib is showing promise as an effective therapy in patients with NSCLC whose tumors are positive for these genetic abnormalities. This review discusses the recent preclinical and clinical findings on ROS1 gene fusions in cancer.
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Optical image-guided cancer surgery is a promising technique to adequately determine tumor margins by tumor-specific targeting, potentially resulting in complete resection of tumor tissue with improved survival. However, identification of the photons coming from the fluorescent contrast agent is complicated by autofluorescence, optical tissue properties, and accurate fluorescent targeting agents and imaging systems. ⋯ What is optical image-guided surgery and how can it improve patient care? What should the oncologic surgeon know about the fundamental principles of optical imaging to understand which conclusions can be drawn from the images? And how do the limitations influence clinical decision making? This article discusses these questions and provides a clear overview of the basic principles and practical applications. Although there are limitations to the intrinsic capacity of the technique, when practical and technical surgical possibilities are considered, optical imaging can be a very powerful intraoperative tool in guiding the future oncologic surgeon toward radical resection and optimal clinical results.
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Brentuximab vedotin (SGN-35), an intravenously administered CD30-specific antibody-drug conjugate, has recently been approved by the U. S. Food and Drug Administration for two indications, including (i) patients with Hodgkin lymphoma relapsing after autologous stem-cell transplantation (ASCT), or after two multidrug regimens in patients with Hodgkin lymphoma who are not candidates for ASCT; and (ii) patients with systemic anaplastic large cell lymphoma (ALCL) who failed at least one prior multidrug chemotherapy regimen. ⋯ The complete response rate was equally as impressive, at 34% and 57% for Hodgkin lymphoma and ALCL, respectively. Results like these and from many other upcoming clinical trials, in which brentuximab vedotin is being investigated in the frontline setting, promise to profoundly change how we manage the CD30-positive lymphoproliferative malignancies. The mechanism of action, preclinical antitumor activity, and clinical activity of brentuximab vedotin against Hodgkin lymphoma, ALCL, and other CD30-expressing lymphomas are reviewed.
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Surgery is a crucial intervention in most cancer patients, but the perioperative period is characterized by increased risks for future outbreak of preexisting micrometastases and the initiation of new metastases-the major cause of cancer-related death. Here we argue that the short perioperative period is disproportionately critical in determining long-term recurrence rates, discuss the various underlying risk factors that act synergistically during this period, and assert that this time frame presents an unexplored opportunity to reduce long-term cancer recurrence. We then address physiologic mechanisms that underlie these risk factors, focusing on excess perioperative release of catecholamines and prostaglandins, which were recently shown to be prominent in facilitating cancer recurrence through their direct impact on the malignant tissue and its microenvironment, and through suppressing antimetastatic immunity. ⋯ We then review animal studies and human correlative findings, suggesting the efficacy of blocking catecholamines and/or prostaglandins perioperatively, limiting metastasis and increasing survival rates. Finally, we propose a specific perioperative pharmacologic intervention in cancer patients, based on simultaneous β-adrenergic blockade and COX-2 inhibition, and discuss specific considerations for its application in clinical trials, including our approved protocol. In sum, we herein present the rationale for a new approach to reduce long-term cancer recurrence by using a relatively safe, brief, and inexpensive intervention during the perioperative period.
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Review
Molecular pathways: targeting phosphoinositide 3-kinase p110-delta in chronic lymphocytic leukemia.
The advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. ⋯ In addition, the clinical advances from targeting p110δ are described, with a focus on clinical outcome, toxicities, and rational combination therapies. The experiences with p110δ in CLL have led to a more fundamental understanding of CLL signaling defects and may be predictive of other BCR-directed therapeutics.