Memorial Sloan Kettering Cancer Center

About: Memorial Sloan Kettering Cancer Center is a healthcare organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 30293 authors who have published 65381 publications receiving 4462534 citations. The organization is also known as: MSKCC & New York Cancer Hospital.

Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Abstract: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model

Abstract: MicroRNAs (miRNAs) are increasingly implicated in the regulation of metastasis. Despite their potential as targets for anti-metastatic therapy, miRNAs have only been silenced in normal tissues of rodents and nonhuman primates. Therefore, the development of effective approaches for sequence-specific inhibition of miRNAs in tumors remains a scientific and clinical challenge. Here we show that systemic treatment of tumor-bearing mice with miR-10b antagomirs-a class of chemically modified anti-miRNA oligonucleotide-suppresses breast cancer metastasis. Both in vitro and in vivo, silencing of miR-10b with antagomirs significantly decreases miR-10b levels and increases the levels of a functionally important miR-10b target, Hoxd10. Administration of miR-10b antagomirs to mice bearing highly metastatic cells does not reduce primary mammary tumor growth but markedly suppresses formation of lung metastases in a sequence-specific manner. The miR-10b antagomir, which is well tolerated by normal animals, appears to be a promising candidate for the development of new anti-metastasis agents.

American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options

Abstract: Health care costs in the United States present a major challenge to the national economic well being. The Centers for Medicare and Medicaid Services (CMS) has projected that US health care spending will reach $4.3 trillion and account for 19.3% of the national gross domestic product by 2019.1 This growth in spending—both in absolute terms and as a proportion of our gross domestic product—has not been accompanied by commensurate improvements in health outcomes, despite expenditures far exceeding those of other countries.2–4 One of the fastest growing components of US health care costs is cancer care, the cost of which is now estimated to increase from $125 billion in 2010 to $158 billion in 2020.1 Although cancer care represents a small fraction of overall health care costs, its contribution to health care cost escalation is increasing faster than those of most other areas because of several factors: the increasing prevalence of cancer due to the overall aging of the population and better control of some causes of competing mortality; the introduction of costly new drugs and techniques in radiation therapy and surgery; and the adoption of more expensive diagnostic tests. In some cases, the adoption of newer, more expensive diagnostic and therapeutic interventions may not be well supported by medical evidence, thereby raising costs without improving outcomes.5 Coupled with, or even driving, some of these rising costs are sometimes unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.6 Historically, most individuals in the United States were shielded from the acute economic impact of expensive care because they had health insurance. However, current trends suggest that patients will find themselves increasingly responsible for a greater proportion of the cost of their health care. Cost shifting or sharing can occur through the increased use of high-deductible policies and larger copayments. These increased costs are already commonplace and may not be affordable for many families. Indeed, health care expenditures are cited as a major cause of personal bankruptcy,7 and the term financial toxicity has entered the vernacular as a means of describing the financial distress that now often accompanies cancer treatment.8 Like other toxicities of cancer treatment, financial toxicity resulting from out-of-pocket treatment expenses can reduce quality of life and impede delivery of high-quality care.9,10 Patients experiencing high out-of-pocket costs have reported reducing their spending on food and clothing, reducing the frequency with which they take prescribed medications, avoiding recommended procedures, and skipping physician appointments to save money.10,11 These unintended consequences risk an increase in health disparities, which runs counter to some of the key goals of health care reform. In many communities, the high costs associated with cancer care have created a difficult situation for patients and the oncologists who care for them. Addressing this situation will require greater understanding of all the risks and benefits of various treatment options as well as the consequences of specific choices. In this regard, studies have shown that patients specifically want financial information about treatment alternatives along with information about medical effectiveness and treatment toxicity. However, they often do not receive it. Closing this knowledge gap will require educated providers who are able to sensitively initiate a dialogue about the cost of care with their patients when appropriate.12,13 Patients with cancer are often surprised by and unprepared for the high out-of-pocket costs of treatments. They also overestimate the benefits of treatments that sometimes extend life by only weeks or months or not at all. Oncologists are generally aware of this conundrum but uncertain about whether and how the cost of care should affect their recommendations.14 Although raising awareness of costs and providing tools to assess value may help to manage costs while maintaining high-quality care, some oncologists see this as being in conflict with their duty to individual patients.15 Recent American Society of Clinical Oncology Efforts Motivated by our responsibility to help oncologists deliver the highest-quality care to patients everywhere, the American Society of Clinical Oncology (ASCO) formed the Task Force on the Cost of Cancer Care in 2007. Its mission includes educating oncologists about the importance of discussing costs associated with recommended treatments, empowering patients to ask questions pertaining to the anticipated costs of their treatment options, identifying the drivers of the rising costs of cancer care, and ultimately developing policy positions that will help Americans move toward more equal access to the highest-quality care at the lowest cost.16 In 2012, through the work of the Task Force, ASCO responded to the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation and identified specific instances of overuse in the delivery of cancer care. ASCO used a deliberative consensus process to identify five common clinical practices that are not supported by high-level evidence. A second list of five was developed using the same process and submitted to the Choosing Wisely Campaign in 2013. ASCO amplified the evidence basis for both top-five lists in two publications17,18 and is now developing measures to evaluate the use of these practices as part of its Quality Oncology Practice Initiative. These exercises have provided opportunities to develop a rigorous but flexible approach to assessing efficacy across diagnostic and treatment domains.

Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is one of the few cancers in which a continued increase in incidence has been observed over several years. As such, there has been a focus on safe and accurate diagnosis and the development of treatment algorithms that take into consideration the unique complexities of this patient population. In the past decade, there have been improvements in nonsurgical treatment platforms and better standardization with respect to the diagnosis and patient eligibility for liver transplant. How to navigate patients through the challenges of treatment is difficult and depends on several factors: 1) patient-related variables such as comorbid conditions that influence treatment eligibility; 2) liver-related variables such as Child-Pugh score; and 3) tumor-related variables such as size, number, pattern of spread within the liver, and vascular involvement. The objectives of this review are to put into perspective the current treatment options for patients with HCC, the unique advantages and disadvantages of each treatment approach, and the evidence that supports the introduction of sorafenib into the multidisciplinary management of HCC.

Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells

Abstract: To increase the tumor specificity of engineered T cells, Kloss et al. design an approach that relies on T cell recognition of two, rather than one, antigens.