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Cancer Journal

Kathy Giusti, Anne Quinn Young, Kerri Lehrhaupt
Realizing the promise of precision medicine requires patient engagement at the key decision points throughout the cancer journey. Previous research has shown that patients who make the "right" decisions, such as being treated at a high-volume academic medical center, for example, have better outcomes. An online survey was conducted to understand awareness of and barriers to these decision points among patients with multiple myeloma and pancreatic, lung, prostate, and metastatic breast cancers. Survey respondents were identified by 5 participating foundations (multiple myeloma: n = 86, pancreatic: n = 108, lung: n = 56, prostate: n = 50, metastatic breast: n = 86) and recruited by an e-mail or social media invitation...
May 2018: Cancer Journal
Stephanie B Wheeler, Jennifer Leeman, Kristen Hassmiller Lich, Florence K L Tangka, Melinda M Davis, Lisa C Richardson
A robust evidence base supports the effectiveness of timely colorectal cancer (CRC) screening, follow-up of abnormal results, and referral to care in reducing CRC morbidity and mortality. However, only two-thirds of the US population is current with recommended screening, and rates are much lower for those who are vulnerable because of their race/ethnicity, insurance status, or rural location. Multiple, multilevel factors contribute to observed disparities, and these factors vary across different populations and contexts...
May 2018: Cancer Journal
Kirsten B Goldberg, Gideon M Blumenthal, Richard Pazdur
The Food and Drug Administration formally established the Oncology Center of Excellence (OCE) in January 2017, as authorized by the 21st Century Cures Act, to expedite the development and review of certain drugs, biologics, and devices for the treatment of cancer. In its first year, the OCE conducted the clinical reviews for several products, including the first 2 chimeric antigen receptor T-cell therapies approved for the treatment of advanced hematologic malignancies and an in vitro diagnostic next-generation sequencing panel, FoundationOne CDx...
May 2018: Cancer Journal
Robert L Grossman
One of the recommendations of the Cancer Moonshot Blue Ribbon Panel report from 2016 was the creation of a national cancer data ecosystem. We review some of the approaches for building cancer data ecosystems and some of the progress that has been made. A data commons is the colocation of data with cloud computing infrastructure and commonly used software services, tools, and applications for managing, integrating, analyzing, and sharing data to create an interoperable resource for the research community. We discuss data commons and their potential role in cancer data ecosystems and, in particular, how multiple data commons can interoperate to form part of the foundation for a cancer data ecosystem...
May 2018: Cancer Journal
Karin D Rodland, Paul Piehowski, Richard D Smith
Breaking down the silos between disciplines to accelerate the pace of cancer research is a key paradigm for the Cancer Moonshot. Molecular analyses of cancer biology have tended to segregate between a focus on nucleic acids-DNA, RNA, and their modifications-and a focus on proteins and protein function. Proteogenomics represents a fusion of those two approaches, leveraging the strengths of each to provide a more integrated vision of the flow of information from DNA to RNA to protein and eventually function at the molecular level...
May 2018: Cancer Journal
Asif Dhar, Beth Meagher, Andrew Ryscavage
Inspired by the Cancer Moonshot, a dedicated team of professionals worked with leaders across the cancer ecosystem to look for an opportunity to radically reduce cancer mortality globally by focusing on early cancer detection. After an initial survey of cancer innovation, progress, and pitfalls, the team believed that if new rapid, affordable, and accurate early detection solutions were appropriately brought to market, it would be possible to intervene earlier when cancer is most treatable.An extensive process began, informed by dozens of experts in the cancer ecosystem...
May 2018: Cancer Journal
Lyric A Jorgenson
No abstract text is available yet for this article.
May 2018: 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
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