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Cancer Journal

Naveen Ramalingam, Stefanie S Jeffrey
Liquid biopsy provides minimally invasive and readily obtainable access to tumor-associated biological material in blood or other body fluids. These samples provide important insights into cancer biology, such as primary tumor heterogeneity; real-time tumor evolution; response to therapy, including immunotherapy; and mechanisms of cancer metastasis. Initial biological materials studied were circulating tumor cells and circulating nucleic acids, including circulating tumor DNA and microRNAs; more recently, studies have expanded to investigate extracellular vesicles, such as exosomes, microvesicles, and large oncosomes; tumor-derived circulating endothelial cells; and tumor-educated platelets...
March 2018: Cancer Journal
Camila D M Campos, Joshua M Jackson, Małgorzata A Witek, Steven A Soper
In the context of oncology, liquid biopsies consist of harvesting cancer biomarkers, such as circulating tumor cells, tumor-derived cell-free DNA, and extracellular vesicles, from bodily fluids. These biomarkers provide a source of clinically actionable molecular information that can enable precision medicine. Herein, we review technologies for the molecular profiling of liquid biopsy markers with special emphasis on the analysis of low abundant markers from mixed populations.
March 2018: Cancer Journal
Jacob M Hope, Joshua D Greenlee, Michael R King
Cancer metastasis is the second leading cause of death in the United States. Despite its morbidity, metastasis is an inefficient process that few cells can survive. However, cancer cells can overcome these metastatic barriers via cellular responses to microenvironmental cues, such as through mechanotransduction. This review focuses on the mechanosensitive ion channels TRPV4 and P2X7, and their roles in metastasis, as both channels have been shown to significantly affect tumor cell dissemination. Upon activation, these channels help form tumor neovasculature, promote transendothelial migration, and increase cell motility...
March 2018: Cancer Journal
Jonathan R Thompson, Smitha P Menon
Cancer immunotherapy has recently undergone rapid advances and has become an integral part of the treatment armamentarium in various malignancies. However, tissue-based biomarker development in this arena has been slow, and valid biomarker identification to guide immunotherapeutic management is desperately needed. "Liquid" or blood-based biopsies potentially offer more convenient and efficient means to judge the immune milieu of individual patients and identify who will benefit most from immunotherapy...
March 2018: Cancer Journal
Ashutosh Agarwal, Marija Balic, Dorraya El-Ashry, Richard J Cote
Circulating tumor cells (CTCs) play a central role in tumor dissemination and metastases, which are ultimately responsible for most cancer deaths. Technologies that allow for identification and enumeration of rare CTC from cancer patients' blood have already established CTC as an important clinical biomarker for cancer diagnosis and prognosis. Indeed, current efforts to robustly characterize CTC as well as the associated cells of the tumor microenvironment such as circulating cancer associated fibroblasts (cCAF), are poised to unmask key insights into the metastatic process...
March 2018: Cancer Journal
James Clancy, Crislyn D'Souza-Schorey
Extracellular vesicles refer collectively to a heterogeneous group of membrane-bound vesicles released from cells and loaded with bioactive proteins, nucleic acids, and lipids. The concept of extracellular vesicles has rapidly evolved from once being viewed as cellular debris to their recognition as packets of cellular information with considerable promise for clinical applications as biomarker platforms and therapeutic vehicles. These shed vesicles have emerged as critical mediators of intercellular communication in both local and distant microenvironments during normal physiological processes, as well as in orchestrating systemic pathophysiological events in disease...
March 2018: Cancer Journal
Maryam B Lustberg, Daniel G Stover, Jeffrey J Chalmers
A primary goal of personalized medicine is to develop tumor-specific biomarkers to aid in treatment selection and to better evaluate response to targeted therapies. The assessment of circulating blood markers as surrogate real-time biopsies of disease status, termed liquid biopsies, has been under investigation. There are many different types of liquid biopsies each with different functionalities and limitations. These include tumor markers, circulating tumor cells, cell-free DNA, and extracellular vesicles including exosomes...
March 2018: Cancer Journal
Sunitha Nagrath, Rhonda M Jack
No abstract text is available yet for this article.
March 2018: Cancer Journal
Mario Sznol
Despite the broad clinical antitumor activity of PD-1/PD-L1 antagonists, many patients who are treated with these agents either do not respond or achieve suboptimal responses. Improving overall outcome will require combinations with other agents to address potential innate or acquired mechanisms of resistance. Many combination trials have been initiated in patients with or without prior exposure to the PD-1/PD-L1 antagonists. In addition to the challenge of identifying optimal dose, schedule, and sequence for the combinations, current biomarker efforts lack the precision to identify optimal combination partners for the PD-1/PD-L1 antagonists in individual patients...
January 2018: Cancer Journal
Theodore S Nowicki, Siwen Hu-Lieskovan, Antoni Ribas
Cancer immunotherapy utilizing blockade of the PD-1/PD-L1 checkpoint has revolutionized the treatment of a wide variety of malignancies, leading to durable therapeutic responses not typically seen with traditional cytotoxic anticancer agents. However, these therapies are ineffective in a significant percentage of patients, and some initial responders eventually develop resistance to these therapies with relapsed disease. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and can be both multifactorial and overlapping in an individual patient...
January 2018: Cancer Journal
Tricia R Cottrell, Janis M Taube
PD-L1 checkpoint blockade is revolutionizing cancer therapy, and biomarkers capable of predicting which patients are most likely to respond are highly desired. The detection of PD-L1 protein expression by immunohistochemistry can enrich for response to anti-PD-(L)1 blockade in a variety of tumor types, but is not absolute. Limitations of current commercial PD-L1 immunohistochemical (IHC) assays and improvements anticipated in next-generation PD-L1 testing are reviewed. Assessment of tumor-infiltrating lymphocytes in conjunction with PD-L1 testing could improve specificity by distinguishing adaptive (interferon γ driven and cytotoxic T-lymphocyte associated) from constitutive (non-immune mediated) expression...
January 2018: Cancer Journal
Daniel Y Wang, Douglas B Johnson, Elizabeth J Davis
Immune checkpoint inhibitors, particularly those targeting PD-1/PD-L1, produce durable responses in a subset of patients across cancer types. Although often well tolerated, these agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system. Treatment of these toxicities primarily consists of immune suppression with corticosteroids and other agents. This review briefly discusses the mechanisms of immune-related adverse events, overviews the clinical and pathologic features of major toxicities caused by PD-1/PD-L1 blockade, and reviews their management...
January 2018: Cancer Journal
Matthew J Pianko, Aaron D Goldberg, Alexander M Lesokhin
Clinical development of immune checkpoint inhibitors targeting the PD-1 pathway has led to clinical benefits for patients with multiple solid tumor and hematologic malignancies and has revolutionized modern oncology. High response rates to PD-1 blockade in patients with classical Hodgkin lymphoma and certain subtypes of non-Hodgkin lymphoma highlight an intrinsic biologic sensitivity to this strategy of treatment. Despite early success of checkpoint inhibitor and immunomodulatory drug combinations in phase 2 studies in multiple myeloma, safety concerns in patients treated with the combination of immunomodulatory drugs and checkpoint inhibitors in myeloma have stalled drug development in this space...
January 2018: Cancer Journal
Matthew C Dallos, Charles G Drake
Genitourinary malignancies represent a diverse biologic and immunologic landscape. Recently, checkpoint blockade has transformed the treatment paradigms for bladder and kidney cancer. However, continued progress will be essential in bladder and kidney cancer, given response to inhibition of the PD-1/PD-L1 (PD-1/PD-L1) axis remains variable and only a minority of patients respond. In contrast with the clinical trial results in bladder and kidney cancer, studies of anti-PD-1/PD-L1 therapy in prostate cancer have generally been disappointing...
January 2018: Cancer Journal
Fernando C Santini, Matthew D Hellmann
Cancer immunotherapies have revolutionized the treatment of non-small cell lung cancer. Yet, only a small subset of patients will benefit from PD-1 or PD-L1 blockade. PD-L1 tumor cell expression is the only approved biomarker at present. Tumor mutational burden and other emerging biomarkers should improve patient selection. Combination therapy approaches with chemotherapy or cytotoxic T-lymphocyte-associated protein 4 blockade may increase the proportion of patients who benefit from immunotherapy. Although use of immunotherapy in lung cancers with targetable oncogenes has not been particularly successful, the benefit of PD-(L)1 inhibitors in early-stage disease is emerging...
January 2018: Cancer Journal
Rodrigo Ramella Munhoz, Michael Andrew Postow
The development of new treatment options has dramatically improved the landscape for patients with advanced melanoma. Part of these advances emerged through the identification of the importance of factors that regulate the immune system, including proteins that negatively modulate T cell-mediated responses termed "immune checkpoints." Indeed, blockade of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint served as a proof of principle that the manipulation of these molecules could induce robust anticancer effects, yet limited to a small percentage of patients...
January 2018: Cancer Journal
Michael A Curran
Antibodies that block the PD-1 coinhibitory receptor on T cells or its primary ligand, PD-L1, have demonstrated unprecedented efficacy across a diverse array of both solid and hematologic malignancies in the clinic. These advances were built on a foundation of murine preclinical tumor model studies, which both demonstrated the therapeutic potential of PD-1/PD-L1 antibody blockade and also provided critical insights into the cellular and molecular processes underlying their capacity to elicit immune-mediated tumor regressions...
January 2018: Cancer Journal
Jedd D Wolchok, Margaret K Callahan
No abstract text is available yet for this article.
January 2018: Cancer Journal
Michael W Rabow, Maria Q B Petzel, Sarah H Adkins
Evidence documents the benefits of palliative care to ameliorate the symptoms of pancreatic cancer as well as those from its treatment. Professional organizations now recommend palliative care for all patients with pancreatic cancer early in the course of illness and concurrently with active treatment. Scrupulous symptom management as well as sensitive communication and advance care planning allow oncologists to provide "primary palliative care" and to care well for patients with pancreatic cancer throughout the course of their illness...
November 2017: Cancer Journal
Andrew H Ko
Most patients with pancreatic cancer either present with or eventually develop metastatic disease during the course of their illness. For such individuals, systemic therapy, namely, cytotoxic therapy, represents the mainstay of treatment and is administered with noncurative intent. Of the various chemotherapy options now available for treating metastatic pancreatic cancer, 2 combination regimens, FOLFIRINOX (infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and the doublet of gemcitabine and albumin-bound paclitaxel, have emerged as frontline standards of care, based on phase III studies demonstrating a significant survival benefit compared with single-agent gemcitabine...
November 2017: Cancer Journal
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