Uncovering a new principle in chemotherapy resistance in breast cancer

A laboratory study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.

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International collaboration to create new cancer models to accelerate research

An international project to develop a large, globally accessible bank of new cancer cell culture models for the research community launched today.

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NCI launches largest-ever study of breast cancer genetics in black women

The Breast Cancer Genetic Study in African-Ancestry Populations initiative is a collaborative research project that will identify genetic factors that may underlie breast cancer disparities. It is the largest study ever to investigate how genetic and biological factors contribute to breast cancer risk among black women.

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Significant expansion of data available in the Genomic Data Commons

The recently launched Genomic Data Commons will get a dramatic increase in the power and utility of its resources with the signing today of a data sharing agreement between the NCI and Foundation Medicine, Inc. (FMI), a molecular information company.

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A clinicopathologic study on SS18 fusion positive head and neck synovial sarcomas

Publication date: March 2017
Source:Oral Oncology, Volume 66
Author(s): Adepitan A. Owosho, Cherry L. Estilo, Evan B. Rosen, SaeHee K. Yom, Joseph M. Huryn, Cristina R. Antonescu
ObjectiveTo determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma.Patients and methodsWe retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996–2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS). Fisher exact test was performed to evaluate variables related to local recurrence.ResultsThirty-four patients (20 males and 14 females, mean of 31years) with SS18-SSX fusion-positive SS-HN were identified. The parapharyngeal region of the neck was the most common site. The mean tumor size was 4.8cm (0.8–10cm). Two-thirds (n=23) of cases had a monophasic histology. The 2, 5 and 10–year DSS rates were 97%, 79% and 68%. The 5-year DSS rates for the adult/pediatric cohort were 74%/88%. Recurrence showed significant effect on DSS (p=0.021). There was no significant effect on DSS with age, therapy modality, tumor site, surgical margin, tumor size (⩽5cm vs. >5cm) and histopathologic subtype. Tumor site (i.e. skull base/paranasal sinus region) was associated with local recurrence (p=0.003).ConclusionIn our cohort DSS rate was associated with recurrence. Tumors located in the skull base/paranasal sinus region were associated with a higher rate of local recurrence. Thus appropriate selection of high risk patients who can benefit from multimodality therapies might improve survival.



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Beyond the Paradigm: Combining Mass Spectrometry and Nuclear Magnetic Resonance for Metabolomics

Publication date: Available online 11 January 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Darrell D. Marshall, Robert Powers
Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of biomarkers for human diseases. Nuclear magnetic resonance (NMR) and mass spectrometry (MS) are the analytical tools that are routinely, but separately, used to obtain metabolomics data sets due to their versatility, accessibility, and unique strengths. NMR requires minimal sample handling without the need for chromatography, is easily quantitative, and provides multiple means of metabolite identification, but is limited to detecting the most abundant metabolites (⩾ 1 μM). Conversely, mass spectrometry has the ability to measure metabolites at very low concentrations (femtomolar to attomolar) and has a higher resolution (∼10³-10⁴) and dynamic range (∼10³-10⁴), but quantitation is a challenge and sample complexity may limit metabolite detection because of ion suppression. Consequently, liquid chromatography (LC) or gas chromatography (GC) is commonly employed in conjunction with MS, but this may lead to other sources of error. As a result, NMR and mass spectrometry are highly complementary, and combining the two techniques is likely to improve the overall quality of a study and enhance the coverage of the metabolome. While the majority of metabolomic studies use a single analytical source, there is a growing appreciation of the inherent value of combining NMR and MS for metabolomics. An overview of the current state of utilizing both NMR and MS for metabolomics will be presented.

Graphical abstract

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Molecular biomarkers to predict response to neoadjuvant chemotherapy for bladder cancer

Publication date: Available online 11 January 2017
Source:Cancer Treatment Reviews
Author(s): Consuelo Buttigliero, Marcello Tucci, Francesca Vignani, Giorgio V. Scagliotti, Massimo Di Maio
Cystectomy is the gold standard for treatment of localized muscle-invasive bladder cancer. However, about 50% of patients develop metastases within 2 years after cystectomy and subsequently die for the disease. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival in patients with muscle-invasive bladder cancer, and pathological response to neoadjuvant treatment (downstaging to ⩽pT1 at cystectomy) is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from neoadjuvant therapy. The identification of reliable biomarkers that could enable the clinicians to identify patients who will really benefit from neoadjuvant chemotherapy is a major issue. This approach could lead to individualized therapy, in order to optimize the chance of response, avoiding the impact of neoadjuvant treatment on quality of life and the delay of cystectomy in non-responder patients. However, no molecular predictive biomarkers have shown clinical utility.This paper aims to review currently available data about biomarkers predictive of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.



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