Personalized treatments of cancer patients: a reality in daily practice, a costly dream or a shared vision of the future from the oncology community?

Therapies targeting activated oncogenes have been associated with several successes in the last decades that are described in this review, together with their limits and related unsolved questions. Most of the tumours will eventually develop drug resistance potentially due to intratumor heterogeneity and selection of additional molecular events. Moreover, studies in the field of molecular characterisation of cancers have shown that most tumors include large number of rare genomic events.

Hurdles on the road to personalized medicine.

Cancer treatment is slowly shifting from an approach in which the tissue of origin and the histology were the guiding principles for the choice of chemotherapy towards a genotype-centric approach in which the changes in the cancer genome are used to select patients for treatment with highly selective and targeted drugs. This transition has all the hallmarks of a disruptive innovation and requires major adjustments in the way that cancer is diagnosed and treated. We discuss here the hurdles on the road ahead to a more personalized treatment of cancer.

Pioneering quality assessment in European cancer centers: a data analysis of the organization for European cancer institutes accreditation and designation program.

Purpose: In order to improve the quality of care in Cancer Centers (CC) and designate Comprehensive Cancer Centers (CCCs), the Organization for European Cancer Institutes (OECI) launched an Accreditation and Designation (A&D) program. The program facilitates the collection of defined data and the assessment of cancer center quality. This study analyzes the results of the first 10 European centers that entered the program.

A gene signature for late distant metastasis in breast cancer identifies a potential mechanism of late recurrences.

Introduction: Breast cancer risk of recurrence is known to span 20 years, yet existing prognostic signatures are best at predicting early recurrences (≤ 5 years). There is a critical need to identify those patients at risk of late-relapse (>5 years), in order to select potential candidates for further treatment and to identify molecular targets for such treatment.

Methods: A total of 252 breast primary tumors were selected at the Netherlands Cancer Institute from a retrospective series of ER+, HER2- breast cancer patients with a follow-up of at least 10 years.

Implications of personalized medicine--perspective from a cancer center.

Three advances are dramatically changing the landscape of oncology. First, hundreds of drugs are available that inhibit targets involved in oncogenesis. Second, efforts to reclassify malignant diseases are expanding the number of orphan molecular diseases.

Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-γ.

Dendritic cell-derived exosomes (Dex) are nanovesicles bearing major histocompatibility complexes promoting T-cell-dependent antitumor effects in mice. Two phase I clinical trials aimed at vaccinating cancer patients with peptide-pulsed Dex have shown the feasibility and safety of inoculating clinical-grade Dex, but have failed to show their immunizing capacity. These low immunogenic capacities have led us to develop second-generation Dex with enhanced immunostimulatory properties.

Dendritic cell-derived exosomes for cancer immunotherapy: what's next?

Exosomes are nanovesicles originating from late endosomal compartments and secreted by most living cells in ex vivo cell culture conditions. The interest in exosomes was rekindled when B-cell and dendritic cell-derived exosomes were shown to mediate MHC-dependent immune responses. Despite limited understanding of exosome biogenesis and physiological relevance, accumulating evidence points to their bioactivity culminating in clinical applications in cancer.

Imatinib mesylate (Gleevec): targeted therapy against cancer with immune properties.

The treatment against cancer is being flooded by targeted therapies. Imatinib mesylate (Gleevec) was the first molecule to provide the proof of principle that targeting an aberrant tyrosine kinase responsible for the uncontrolled cell cycle progression allows for the eradication of tumors. The ideal targeted therapy should eliminate the molecular event responsible for the disease, an oncogenic product such as c-KIT, ABL/BCR and PDGFRa in the case of Gleevec.

MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: a molecular portrait of stage 4S.

Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age <365days at diagnosis) show regression contrasting with progression in children (>365days). Our study aimed at: (i) identifying age-based genomic and gene expression profiles of stage 4 NB supporting this clinical stratification; and (ii) finding a stage 4S NB signature.

Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha.

Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional MHC/peptide complexes promoting T cell-dependent tumor rejection. In the first Phase I trial using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell responses prompted the search for alternate effector mechanisms. Mouse studies unraveled the bioactivity of Dex on NK cells.

Gap junction communication between autologous endothelial and tumor cells induce cross-recognition and elimination by specific CTL.

Cellular interactions in the tumor stroma play a major role in cancer progression but can also induce tumor rejection. To explore the role of endothelial cells in these interactions, we used an in vitro three-dimensional collagen matrix model containing a cytotoxic T lymphocyte CTL clone (M4.48), autologous tumor cells (M4T), and an endothelial cell (M4E) line that are all derived from the same tumor.

Towards quality, comprehensiveness and excellence. The accreditation project of the Organisation of European Cancer Institutes (OECI).

There are important gaps in the health status of citizens across Europe, as measured by life expectancy, mortality or morbidity data (Report for the European Commission on the health status of the European Union, 2003). Among the main determinants of the major causes of mortality and morbidity, stated in this report, stands recurrently access to quality healthcare. There is a fundamental need to define quality indicators and set minimal levels of performance quality criteria for healthcare.

Improvement of European translational cancer research. Collaboration between comprehensive cancer centers.

Even though the increasing incidence of cancer is mainly a consequence of a population with a longer life span, part of this augmentation is related to the increasing prevalence of patients living with a chronic cancer disease. To fight the problem, improved preventive strategies are mandatory in combination with an innovative health care provision that is driven by research. To overcome the weakness of translational research the OECI is proposing a practical approach as part of a strategy foreseen by the EUROCAN+PLUS feasibility study, which was launched by the EC in order to identify mechanisms for the coordination of cancer research in Europe.

Managing cancer in the EU: the Organisation of European Cancer Institutes (OECI).

Organization of European Cancer Institutes (OECI) has the mission to facilitate the development of European comprehensive cancer centres by integrating care and prevention with research and education. Core issues are to deliver a complete multidisciplinary care of high quality and stimulate translational cancer research. The goal is to innovate the cancer care.

The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy.

For the last four decades, the treatment of cancer has relied on four treatment modalities, namely surgery, radiotherapy, cytotoxic chemotherapy, and hormonotherapy. Most of these therapies are believed to directly attack and eradicate tumor cells. The emerging concept that cancer is not just a disease of a tissue or an organ but also a host disease relies on evidence of tumor-induced immunosuppression and polymorphisms in genes involved in host protection against tumors.

Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.

Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses.

Therapy-induced tumor immunosurveillance involves IFN-producing killer dendritic cells.

A unique class of IFN-producing killer dendritic cells (IKDC) resembling natural killer cells has been defined that can recognize and lyse tumor cells through a tumor necrosis factor-related apoptosis-inducing ligand-dependent mechanism. IKDC may mediate the host-dependent antitumor activity of Gleevec/STI571 and other therapeutics that can inhibit the c-kit tyrosine kinase. IKDC represent an important new component of the innate immune system responding to cancer.

DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.

Background: Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy.

Methods: We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression.

Gene expression profiling of primary cutaneous melanoma and clinical outcome.

Background: Gene expression profiling data for human primary cutaneous melanomas are scarce because of the lack of retrospective collections of frozen tumors. To identify differentially expressed genes that may be involved in melanoma progression and prognosis, we investigated the relationship between gene expression profiles and clinical outcome in a cohort of patients with primary melanoma.

Methods: Labeled complementary RNA (cRNA) from each tissue sample was hybridized to a pangenomic 44K 60-mer oligonucleotide microarray.

A novel dendritic cell subset involved in tumor immunosurveillance.

The interferon (IFN)-gamma-induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer (NK) cells in mice. Here we show that the main source of IFN-gamma is not the conventional NK cell but a subset of B220(+)Ly6C(-) dendritic cells, which are atypical insofar as they express NK cell-surface molecules. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220(+)NK1.