The lancet oncology
-
Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases in mammalian cells, maintains cell homoeostasis by counteracting most of the kinase-driven intracellular signalling pathways. Unrestrained activation of oncogenic kinases together with inhibition of tumour suppressors is often required for development of cancer. ⋯ Preclinical studies show that pharmacological restoration of PP2A tumour-suppressor activity by PP2A-activating drugs (eg, FTY720) effectively antagonises cancer development and progression. Here, we discuss PP2A as a druggable tumour suppressor in view of the possible introduction of PP2A-activating drugs into anticancer therapeutic protocols.
-
The lancet oncology · May 2013
ReviewHas the time come for metronomics in low-income and middle-income countries?
In 2008, 72% of cancer deaths occurred in low-income and middle-income countries, where, although there is a lower incidence of cancer than in high-income countries, survival rates are also low. Many patients are sent home to die, and an even larger number of patients do not have access to treatment facilities. New constraint-adapted therapeutic strategies are therefore urgently needed. ⋯ In this Personal View, we will briefly review the rationale behind the combination of metronomic chemotherapy and drug repositioning-an approach we term metronomics. We assess the clinical experience obtained with this kind of anticancer treatment and describe potential new developments in countries with limited resources. We also highlight the need for adapted clinical study endpoints and innovative models of collaboration between for-profit and non-profit organisations, to address the growing problem of cancer in resource-limited countries.
-
The lancet oncology · May 2013
ReviewCytokine patterns in patients with cancer: a systematic review.
Active, but dysfunctional, immune responses in patients with cancer have been studied in several tumour types, but owing to the heterogeneity of cancer theories of common reaction mechanisms seem to be obsolete. In this Review of published clinical studies of patients with cancer, expression and interplay of the following cytokines are examined: interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 12, interleukin 18, tumour necrosis factor α (TNFα), transforming growth factor β (TGFβ), interferon-γ, HLA-DR, macrophage migration inhibitory factor (MIF), and C-X-C motif chemokine receptor 4 (CXCR4). Clinical data were analysed in a non-quantitative descriptive manner and interpreted with regard to experimentally established physiological cytokine interactions. ⋯ Cytokines produced by tumours might have a pivotal role in this defect. A working hypothesis is that the cancer-specific and histology-independent uniform cytokine cascade is one of the manifestations of the underlying paraneoplastic systemic disease, and this hypothesis links the stage of cancer with both the functional status of the immune system and the patient's prognosis. Neutralisation of this cytokine pattern could offer novel and so far unexploited treatment approaches for cancer.
-
The lancet oncology · May 2013
Multicenter StudySafety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study.
Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. ⋯ Pfizer and National Cancer Institute grant to the Children's Oncology Group.
-
The lancet oncology · May 2013
Multicenter StudyMethylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study.
Identification of robust biomarkers of malignancy and methods to establish disease progression is a major goal in paediatric neuro-oncology. We investigated whether methylation of the TERT promoter can be a biomarker for malignancy and patient outcome in paediatric brain tumours. ⋯ The Canadian Institute of Health Research and the Terry Fox Foundation.