Review Articles in 2011

The survival rate of patients with pediatric cancer has increased considerably due to improved understanding of the biology of cancer subtypes, and the development of targeted therapies. This Review analyzes the recent findings that link pharmacogenomic variations with drug exposure, adverse effects, and efficacy of the emerging new treatments in pediatric oncology.

Small-cell lung cancer has a poor prognosis and treatment options for this disease are limited. The authors discuss the molecular biology and current clinical management of progressive small-cell lung cancer, and critically evaluate the recent SPEAR trial, in which the use of second-line picoplatin was investigated.

MicroRNAs (miRNAs) is an exciting and fast-moving field in cancer diagnosis and therapeutics. This Review highlights the use of circulating miRNAs in body fluids as a noninvasive diagnostic tool and as a treatment-response predictor. It also explores the concept that body-fluid-based miRNAs possibly originated as the first 'hormones'.

The survival rate for adolescents and young adults with acute lymphoblastic leukemia has improved over the past decades. However, it is still behind the overall survival of children with this disease. In this Review, Schafer and Hunger analyze recent studies that have shown improved outcomes for adolescents and adults treated with pediatric-based regimens offering a potential solution for the “adolescents and young adults gap”.

Antiangiogenic therapy is thought to starve tumors by cutting their nutrient and oxygen supply. The authors review evidence for a potential link between hypoxia signaling and an invasive switch that occurs in cancer cells, through which antiangiogenic drugs could increase the risk of tumor metastasis in certain conditions, and discuss approaches to reduce tumor dissemination.

The exclusive expression of well-defined antigens renders prostate cancer an attractive target for immunotherapy. Di Lorenzoet al. review clinical results of immunotherapy trials in patients with prostate cancer and discuss methodological issues related to the evaluation of treatment efficacy of immunotherapeutic agents.

Therapeutic advances in melanoma seem on the horizon, with the identification of BRAF as a principal therapeutic target. The authors describe the scientific basis for the targeting ofBRAFmutations in cancer, the early clinical data with BRAF inhibitors, and how combinatorial therapies may address the current limitations of their use in the clinic.

The existence of a state of limited metastasis or oligometastasis observed in selected patients is associated with favorable outcomes. This Review discusses the role of local therapy for oligometastases that arise in lung and liver, the challenge of identifying the patients who will benefit from the treatment of their oligometastatic disease and how to select the right local therapy for these patients.

Autophagy is an important cellular recycling mechanism that can be either tumor-promoting or tumor-suppressive and represents a novel anti-cancer target. In this article, Janku and colleagues explain the rational behind targeting autophagy for the development of anticancer therapy and discuss drugs that either inhibit or activate autophagy.

Metastatic bone disease in advanced-stage prostate cancer causes some of the most distressing symptoms and is associated with poor survival. This Review discusses the complex pathology of the bone lesion in metastatic prostate cancer and promising therapeutic strategies to treat this disease.

The self-seeding model provides a new paradigm whereby progression from a primary tumor to metastasis is understood as a multidirectional process, balanced between mitotic (primary tumor), seeding (metastasis) and self-seeding processes. The authors discuss how this model helps to explain various enigmas including the similarities between pre-neoplasia and invasive cancer, mammographic breast density as a risk factor, and the relationship between local control and distant recurrence.

The numerous active agents and possible drug combinations for the treatment of multiple myeloma present challenges in terms of the best regimens for first-line therapy, role of transplantation, and maintenance therapy. Should treatment approaches achieve cure or disease control? This Review provides an update on the treatment of multiple myeloma, with a focus on recent advances and newly diagnosed disease.

Metastasis-suppressor genes (MSGs) are involved in diverse molecular processes in multiple tumor types; therefore, treatment strategies based on MSGs have unparalleled potential to improve patient care. In this Review, barriers specific to the translation of MSG biology into clinical practice are discussed and future research directions necessary for clinical advances are delineated.

Medical imaging techniques can monitor tumor changes in response to treatment and provide important surrogate end points in clinical studies. Bruno Morgan discusses advantages and limitations of currently available imaging modalities and highlights the challenges associated with the incorporation of imaging biomarkers into clinical cancer trials.

The treatment of microscopic metastatic disease is based on the assumption that micrometastases and overt metastases will respond to the same interventions; however, clinical observations illustrate this assumption is incorrect. The authors discuss our existing understanding of the metastatic cascade, emerging therapeutic targets involved in the metastatic process, and how novel anti-metastatic therapies might be developed for clinical use.

Brain metastases remain a serious obstacle in the successful treatment of patients with solid tumors. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients.

Overexpression of human EGFR family receptors is associated with a poor prognosis of patients with esophagogastric cancer. The authors of this Review discuss the preclinical rationale of EGFR inhibition in this setting and summarize recent clinical trials involving EGFR-targeting drugs.

Changes in the bone marrow (BM) stroma can create an environment that favors neoplastic cell growth and survival. The authors of this Review examine the contribution of the BM stroma to several hematological neoplasms and describe the processes that are responsible for remodeling the BM stroma. Approaches that target components of the altered BM stroma and prevent the crosstalk between BM stromal cells and neoplastic cells are also discussed.

Hepatocellular carcinoma (HCC) is notoriously resistant to systemic therapies. The success of the anti-VEGF therapy sorafenib in patients with advanced-stage HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic drugs.

New techniques, such as crystallography and three-dimensional modeling, can be used to assist the development of selective targeted agents for cancer treatment. In this Review, Pierotti and colleagues discuss the molecular features of KIT and PDGFRA receptor tyrosine kinases, which are druggable targets in gastrointestinal stromal tumors. The authors focus on the major challenge in kinase drug discovery—the emergence of resistance—and discuss techniques for predicting and preventing this adverse event.