Clinical Oncology

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with a similar incidence to acute myeloid leukaemia (AML), but much less is known about the genetic basis of MDS. Discriminating between MDS and AML is based largely on cytomorphological analysis, and a myeloblast count of

Co-administration of a nanoparticle–albumin–paclitaxel formulation with gemcitabine (the only available treatment for pancreatic cancer) increases the intratumour availability of the gemcitabine. A mouse model of pancreatic ductal adenocarcinoma was used to elucidate the mechanism of this effect: paclitaxel promotes the oxidative degradation of cytidine deaminase,

Until recently, there has been no consensus on the best treatment approach for invasive oesophageal cancer. Now, a study in 169 patients with T4 oesophageal cancer who did not have distant metastases has shown that induction triplet chemotherapy significantly improved surgical resection rates and reduced

A new study reports the 20-year follow-up results of the EORTC 10801 phase III randomized trial. This study compared breast-conserving therapy (BCT) followed by radiotherapy with modified radical mastectomy (MRM) in patients with early stage breast cancer. No significant difference was noted in time to

In a cross-sectional cohort of 24,410 elderly patients (>65 years old) with cancer in Ontario, Canada. Barbera et al. measured opioid prescription (OP) rates and evaluated factors associated with OPs. The OP rate increased with severity of pain, but 33% of patients did

Approximately 40% of patients with colorectal cancer (CRC) develop liver metastases at some point during the course of the disease. A third of these patients can undergo hepatic resection, and half of these patients will achieve a 5-year overall survival but, what is the impact

The approved first-line therapy for advanced-stage renal cell carcinoma (RCC) is high-dose (50 mg per day) intermittent dosing of sunitinib (4 weeks on and 2 weeks off treatment, called schedule 4/2). Although a low-dose (37.5 mg per day) continuous daily dosing (CDD) of sunitinib has

Treatment with tyrosine kinase inhibitors (TKIs) can be effective in the majority of patients with cancers such as non-small-cell lung cancer (NSCLC) with mutations in EGFR, and chronic myeloid leukemia (CML) driven by the gene fusion BCR–ABL. However, 20% of patients have primary

As treatment for patients with breast cancer becomes increasingly effective, the quality of life aspects have been gaining more importance. This has led, in many countries, to an increased importance being placed on the cosmetic outcomes after surgery. However, is this aspect of similar importance

Chemotherapy is the first-line treatment option for unresectable or recurrent pediatric low-grade glioma (LGG), although no strict guidelines exist as to which regimen should be used. Eric Bouffet and colleagues were intrigued by an old study in which a good response in children with LGG

In 2011, a joint panel of the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society devised a novel classification system for lung adenocarcinomas (ADCs) based on tumour architecture. A new retrospective study, which evaluated histological samples from more

A new tissue microarray study has shown that approximately 20% of all head and neck squamous cell carcinomas (HNSCCs) are positive for human papilloma virus (HPV) and that in most of these lesions, the mTOR pathway is also activated. In a xenograft mouse model of

Updated results of the European Randomized nudy of Screening for Prostate Cancer reveal that PSA screening significantly reduces mortality from prostate cancer, but does not affect all-cause mortality. A total of 182,160 men (50–74 years old) from eight European countries were randomly assigned to PSA-based

A study in 633 patients who survived breast cancer showed that higher intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces inflammation and fatigue. The participants completed a questionnaire about food frequency and dietary supplement, and provided a blood sample to assess C-reactive protein (CRP) levels

The American College of Physicians (ACP) has undertaken a comprehensive analysis of four major guidelines for the screening for colorectal cancer. Structured as several statements, the review states that all at-risk adults should receive individualized assessment. Average-risk adults aged ≥50 years should be screened using

In these pages, we have repeatedly published articles that call for improved preclinical resources for testing novel drug compounds and for optimizing targeted therapy. Similar to when waiting for buses, now two excellent resources of this type have come along at once. In two papers

A team of what Cancer Research UK have described as “some of the UK's most exciting young researchers” have performed a careful genetic analysis of tumours and shown that “no two samples from the same patient were genetically identical.” This finding has obvious implications for

Neuroendocrine tumours frequently express the somatostatin receptor, a therapeutic target for radiopeptide therapy. The somatostatin analogue DOTA-TOC was developed and introduced into the clinic at the University Hospital Basel in 1997. Martin Walter has searched to optimize ways to deliver β-emitting radioisotopes in patients with

Patients with cancer in the UK often have multiple consultations with their family doctor before diagnosis, which is partly due to different symptoms each cancer type presents. Tumours with one main symptom and a simple investigative pathway are easier to diagnose, but structural investigational barriers also contribute to delayed diagnosis.

Patients undergoing removal of adenoma have a 53% reduction in colorectal cancer-related death. However, to translate these results into a screening programme, participation rates should also be taken into account. The results of a large, first screening round of once-only colonoscopy demonstrated a low participation rate compared with biennial faecal immunochemical test.

A safety substudy of the MAP.3 trial included 242 women who had completed 2-year follow up (124 given exemestane, 118 given placebo). Exemestane resulted in a significantly higher decrease of bone structural parameters and bone mineral density. Patients receiving exemestane for primary breast cancer prevention should be monitored and treated accordingly.

Reductions in breast cancer risk for women with a hysterectomy receiving oestrogen-alone therapy have persisted since termination of active treatment on the Women's Health Initiative trial. The few deaths among women diagnosed with breast cancer during this trial limit the interpretation of the reduced mortality for women receiving oestrogen alone compared with placebo.

Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations,

Rearrangements of the anaplastic lymphoma kinase (ALK) gene occur infrequently in non-small-cell lung cancer (NSCLC), but provide an important paradigm for oncogene-directed therapy in this disease. Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in

Oesophageal cancer is a global health problem with high mortality due to the advanced nature of the disease at presentation; therefore, detection at an early stage significantly improves outcome. Oesophageal squamous-cell cancer is preceded by dysplasia and oesophageal adenocarcinoma is preceded by Barrett's oesophagus, which

Emerging evidence indicates that patients with cancer have considerable impairments in cardiorespiratory fitness, which is likely to be a result of the direct toxic effects of anticancer therapy as well as the indirect consequences secondary to therapy (for example, deconditioning). This reduced cardiorespiratory fitness is

Antiangiogenic therapies that target VEGF or its receptors have become a mainstay of cancer therapy in multiple malignancies. However, the clinical efficacy of these agents is less than originally anticipated and, in most settings, requires the addition of cytotoxic chemotherapy suggesting that, as for other

Gastrointestinal cancer: Less is more for surgical treatment of oesophageal cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.89 Author: Lisa Hutchinson

Pancreatic cancer: Mouse models link metabolism and deubiquitination with Kras Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.85 Author: Rebecca Kirk

Genetics: Understanding the ABSOLUTE genome Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.86 Author: Mina Razzak

Gynaecological cancer: OCEANS' three: the ovarian job Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.84 Author: M. Teresa Villanueva

Neuroblastoma is a debilitating disease and a leading cause of childhood cancer deaths. The discovery of ALK as a mutated oncogenic receptor in neuroblastoma has provided an attractive target for innovative therapies. In this article, Mosse and Carpenter review the preclinical and clinical advances in ALK-targeted therapies for neuroblastoma and discuss the emerging challenges.

Targeting the MET pathway is an increasingly attractive anticancer strategy. In this Review, this pathway is viewed from the clinical perspective, assessing the available agents in terms of efficacy and toxicity and looking forward to biomarker-driven application in the clinic.

Palliative care: Analgesia prescribing in the USA—no gain, much pain Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.81 Author: Lisa Hutchinson

CNS cancer: Don't hedge(hog) your bets Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.82 Author: Rebecca Kirk

A qualitative study indicates that there is a positive selection bias towards favourable economic analysis of targeted therapies, when these are funded by the manufacturer. At a time of increasing budgetary constraints and public scrutiny of the relationship between industry and the professions, we need a more mixed economy of funding for this field.

The benefit of salvage chemotherapy in gastric cancer refractory to first-line platinum and fluoropyrimidine therapy was previously unknown. A randomized multicentre study has shown that irinotecan or docetaxel administered as single agents improved survival compared with best supportive care alone. Hence, salvage chemotherapy is now a proven option in pretreated gastric cancer.

Gemtuzumab ozogamicin was withdrawn from the market after being evaluated in combination with chemotherapy in the frontline treatment of patients aged 18 to 60 years with acute myeloid leukaemia (AML). More-recent randomized trials demonstrate that low doses of gemtuzumab added to cytarabine and anthracycline-based chemotherapy benefit patients with better-risk AML.

The treatment of severe hepatitis B virus reactivation after chemotherapy Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.1-c1 Authors: Xing Li, Yan-Fang Xing, Qu Lin, Min Dong, Xiang-Bo Wan & Xiang-Yuan Wu

Authors' reply: Current strategies in the management of hepatitis B virus reactivation Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.1-c2 Authors: Harrys A. Torres & Marta Davila

Genetics: Polyglutamine repeats or cancer? Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.73 Author: Rebecca Kirk

From AACR—gynecological cancer: Controlling recurrent ovarian cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.79

From AACR—lymphoma: A precise approach for diffuse large B-cell lymphoma Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.77

From AACR—urological cancer: Antiangiogenic therapy works in metastatic urothelial cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.80

Tyrosine kinase inhibitors, such as imatinib, are effective treatments of advanced-stage gastrointestinal stromal tumour. Here, the optimal treatment strategy for these patients is outlined and future challenges discussed.

Cancer cells rely on angiogenesis to fulfil their need for oxygen and nutrients; hence, agents targeting angiogenic pathways and mediators have been investigated as potential cancer drugs. However, a significant number of patients either do not respond to antiangiogenic agents or fairly rapidly develop resistance to them, which raises questions about how resistance develops and how it can be overcome. In this Review, the authors examine the evidence linking antiangiogenic agents and intratumour hypoxia by providing an overview of the preclinical and clinical data, focusing on the possibility of exploiting intratumour hypoxia as a means to improve the therapeutic response to antiangiogenic agents.

Targeted therapies: GLIOMA—It's all in the site occupancy Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.65 Author: Lisa Hutchinson

Diagnosis: Dying from a cancer diagnosis Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.66 Author: Rebecca Kirk

Gynaecological cancer: Olaparib as maintenance therapy for ovarian cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.70

Skin cancer: Two-faced role of metformin in BRAF-mutant melanoma Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.68

Immunotherapy: Cixutumumab and mTOR blockade well tolerated in EWS Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.67

Haematological cancer: New gold standard for Hodgkin lymphoma? Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.69

In this Review, Tentler et al. present the opportunities and challenges of using patient-derived tumour xenograft models in oncology drug development, provide specific disease examples, and describe concepts regarding predictive biomarker development and future applications.

The advances in the field of targeted therapy for the treatment of renal cell carcinoma have improved outcomes for patients dramatically. In this Review article, an expert consensus opinion for the optimal use of these targeted anticancer therapies for the treatment of patients with renal cell carcinoma is outlined.

This Perspectives article describes how phase I trials assessing the efficacy of targeted therapies should examine not only safety and toxicity, but also the appropriate patient population. Based on the experience of their own academic institution, Rodón and colleagues explain how to build a pre-screening programme in early drug development.