Molecular classification of colorectal cancer: Current perspectives and controversies

Publication date: Available online 2 January 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Amrallah A. Mohammed, Hani El-Tanni, Hani M. El-Khatib, Ahmad A. Mirza, Amr T. El-Kashif
ObjectiveThe aim of this review is to summarize the molecular classification of colorectal cancer (CRC), recognizing that the review is a small fragment from the whole picture.MethodsA Medline search was conducted and published articles from American and European studies from 2000 to present were reviewed. Different types of molecular classifications are presented.ResultsIntegrative genomic studies revealed the complexity of molecular heterogeneity of CRC. Although several treatments exist, we do not have a good way to select the appropriate treatment; personalized treatment strategies are needed. Genomically-driven clinical trials with matched targeted therapies for KRAS, NRAS, BRAF and PIK3CA mutations are ongoing and offer promising treatment opportunities for patients with CRC.ConclusionFor CRC, a broad molecular classification is "still missing". There is a real hope that the evolving application of molecular techniques to diagnosis, risk-stratification and management of CRC will be translated to reduce disease burden and improve the survival.



from Cancer via ola Kala on Inoreader http://ift.tt/1mXRJfM
via IFTTT

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

Publication date: Available online 2 January 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Francesco Passiglia, Giuseppe Bronte, Viviana Bazan, Antonio Galvano, Bruno Vincenzi, Antonio Russo
BackgroundClinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status.Materials and MethodsData from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected, according to the PRISMA guidelines. Pooled HRs were calculated for both the OS and/or RFS.ResultsSeven eligible trials (1403 patients) were included. Pooled analysis showed that KRAS mutations predicted a significantly worse both RFS (HR: 1.65; 95% CI: 1.23–2.21) and OS (HR: 1.86; 95% CI: 1.51–2.30) in patients who underwent surgical resection of CLM. BRAF mutations were also associated with a significantly worse OS (HR: 3.90; 95% CI: 1.96–7.73) in this subgroup of patients.ConclusionsThis meta-analysis suggests both KRAS and BRAF mutations as poor, prognostic biomarkers, associated with worse survival outcomes, in patients undergoing hepatic resection of CLM.



from Cancer via ola Kala on Inoreader http://ift.tt/1PFaWhw
via IFTTT

Langerhans cell sarcoma of the head and neck

Publication date: Available online 2 January 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): James E.F. Howard, Liam Masterson, Raghav C. Dwivedi, Piyush Jani
Head and neck Langerhans cell sarcoma (HNLCS) is a rare malignant tumor of Langerhans cells carrying a poor prognosis. The aim of this work was to perform a systematic review of HNLCS cases, examine outcomes, and develop an evidence-based management algorithm. We performed a systematic literature search yielding 16 studies with 17 cases of HNLCS; 33 studies with 55 Non-HNLCS were used as a comparison.Mean disease-specific survival was 20.5 months (SE±5.1) for HNLCS versus 26.2 months (SE±4.2) for non-HNLCS. There was no significant difference in disease-specific (p=0.768) or disease-free survival (p=0.880) between the two cohorts. There was a significant difference in both disease-specific (p=0.044) and disease-free survival (p=0.001) between local, locoregional and disseminated disease favoring more limited disease.HNLCS appears to present later, with more disseminated disease. Surgery remains the mainstay of treatment of local disease, however clear margins do not guarantee clearance.



from Cancer via ola Kala on Inoreader http://ift.tt/1TxnruR
via IFTTT

Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas

Publication date: Available online 2 January 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Pier Luigi Zinzani, Vijayveer Bonthapally, Dirk Huebner, Richard Lutes, Andy Chi, Stefano Pileri
Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sézary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically <35%, romidepsin and vorinostat can induce some durable responses in heavily pretreated patients and alleviate bothersome symptoms, such as pruritus. New studies indicate that the anti-CD30 antibody-drug conjugate brentuximab vedotin, anti-CCR4 antibody mogamulizumab, and fusion protein immunotoxin A-dmDT390-bisFv(UCHT1) may be particularly active in this setting. In this paper, we present an exhaustive review of the clinical data on current and possible future drug treatment options for relapsed/refractory CTCL.



from Cancer via ola Kala on Inoreader http://ift.tt/1PFaXSF
via IFTTT

Panoptic Clinical Review of the Current and Future Treatment of Relapsed/Refractory T-cell Lymphomas: Peripheral T-cell Lymphomas

Publication date: Available online 3 January 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Pier Luigi Zinzani, Vijayveer Bonthapally, Dirk Huebner, Richard Lutes, Andy Chi, Stefano Pileri
Peripheral T-cell lymphomas (PTCLs) tend to be aggressive and chemorefractory, with about 70% of patients developing relapsed/refractory disease. Prior to 2009, chemotherapies were the only options for relapsed/refractory PTCL, other than hematopoietic transplants. However, chemotherapy only improves survival by about 1 month compared with palliation. Four drugs are now approved in the US to treat relapsed/refractory PTCL: pralatrexate, romidepsin, belinostat, and brentuximab vedotin (for systemic anaplastic large cell lymphoma [sALCL]). Response rates with pralatrexate, romidepsin, and belinostat range from 25–54% in mixed relapsed/refractory PTCL populations, while 86% of sALCL patients respond to brentuximab vedotin. Here, we critically evaluate the evidence supporting the current drug treatment of relapsed/refractory PTCL, and look to the future to see how the treatment panorama may change with the advent of new targeted therapies, some of which (e.g. alisertib in PTCL and mogamulizumab in CCR4-positive adult T-cell leukemia/lymphoma) are already in phase 3 trials.



from Cancer via ola Kala on Inoreader http://ift.tt/1PFaXSB
via IFTTT

Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors

Publication date: February 2016
Source:European Journal of Cancer, Volume 54
Author(s): Hink Boer, Nico-Derk L. Westerink, Renske Altena, Janine Nuver, D.A. Janneke Dijck-Brouwer, Martijn van Faassen, Frank Klont, Ido P. Kema, Joop D. Lefrandt, Nynke Zwart, H.Marike Boezen, Andries J. Smit, Coby Meijer, Jourik A. Gietema
PurposeChemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors.MethodsIn 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3–20] after chemotherapy) and correlated with SNPs in SRD5A2.ResultsThe metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (<15 nmol/l) and a variant genotype showed a high prevalence of the metabolic syndrome (66.7%). Mean intima-media thickness of the carotid artery and urinary albumin excretion, both markers of vascular damage, were higher in the group of survivors homozygous or heterozygous variant for rs523349 (0.62 versus 0.57 mm, P = 0.026; 5.6 versus 3.1 mg/24 h, P = 0.017, respectively). No association was found between cardiometabolic status and SNP rs9282858 in SRD5A2.ConclusionMetabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention.



from Cancer via ola Kala on Inoreader http://ift.tt/1NYyATT
via IFTTT

Rationale for anti-CD137 cancer immunotherapy

Publication date: February 2016
Source:European Journal of Cancer, Volume 54
Author(s): Amani Makkouk, Cariad Chester, Holbrook E. Kohrt
The consideration of the complex interplay between the tumour microenvironment (TME) and the immune response is the key for designing effective immunotherapies. Therapeutic strategies that harness co-stimulatory receptors have recently gained momentum in the clinic. One such strategy with promising clinical applications is the targeting of CD137, a member of the tumour necrosis factor receptor superfamily. Its expression on both innate and adaptive immune cells, coupled with its unique ability to potentiate antitumour responses through modulating the TME and to ameliorate autoimmune responses, has established it as an appealing target. In this review, we will discuss the various CD137-targeted immunotherapeutics that have reached clinical development, with a focus on recent advances and novel modalities such as CD137 chimeric antigen receptors and CD137 bispecific antibodies. We will also highlight the effect of CD137 targeting on the TME and discuss the importance of probing TME changes for predicting and testing the efficacy of CD137-mediated immunotherapy.



from Cancer via ola Kala on Inoreader http://ift.tt/1NYyz2c
via IFTTT

Comment on “Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis”, published in Eur J Cancer 51 (2015), 1570–1579

Publication date: Available online 2 January 2016
Source:European Journal of Cancer
Author(s): Pierre Blanchard, Laureen Ribassin-Majed, Anne Lee, Jean Pierre Pignon




from Cancer via ola Kala on Inoreader http://ift.tt/1NYyxYh
via IFTTT