Reviews & Analysis

An important phase III trial involving transplant-eligible patients with multiple myeloma compared bortezomib and dexamethasone (BzD) induction with the previous standard of care. BzD was associated with a higher overall response and a deeper response to therapy that translated to superior responses following high-dose therapy and autologous stem cell transplantation.

Men with locally advanced or high-risk prostate cancer may benefit from combined modality strategies. This Review discusses the approaches and rational for preoperative and intraoperative radiotherapy and compares them with the utility of postoperative radiotherapy. The urgent need for novel biomarkers for selection purposes is highlighted.

Chemotherapy and trastuzumab is standard therapy for HER2-positive breast cancer, although aromatase inhibitors combined with anti-HER2 therapies is an option in patients with HER2 and hormone receptor-positive tumors. The activity observed with chemotherapy and anti-HER2 therapies seems to be higher than with aromatase inhibitors and HER-2-based therapies. The authors highlight the data that have led to current treatment strategies and the importance of considering chemotherapy and anti-HER2 therapy for HER2 and hormone receptor-positive tumors.

Selectively targeting cancer stem cells with novel therapeutics is gaining importance because disease recurrence after treatment-induced remissions is a major cause of morbidity and mortality. This Review discusses the pathways that are active during development, specifically the Wnt, Notch, and Hedgehog pathways, and the clinical development of therapeutic agents that target these pathways.

A personalized treatment approach for lymphoma has potential to improve treatment responses. In this Review, Anas Younes summarizes the current development status of novel agents for lymphoma and discusses strategies to move the field forward.

The high attrition rate for cancer drugs is discussed in this Review of the preclinical models available to cancer researchers and clinicians. The classic methods of drug discovery and analysis are described along with new preclinical strategies, including the genetically engineered mouse models and small-interfering RNA that have identified promising targeted drugs. Better knowledge of oncogenic signaling pathways and the mechanism of action of their inhibitors is probably the most effective way to improve the development of successful anticancer drugs.

A randomized phase III trial of patients with stage II and III colon cancer showed no benefit of adding bevacizumab to standard adjuvant oxaliplatin plus fluorouracil and leucovorin. Despite suggestive evidence of a short-term benefit, these data and other similar findings dictate that adjuvant bevacizumab should not be used in colon cancer.

Microscopic deposits of tumor cells in regional lymph nodes can be detected using immunohistochemical techniques in patients without conventional histopathological evidence of lymph-node involvement. In the case of bile duct cancer, these micrometastases have an intermediate prognostic significance between that of positive and negative conventional pathology.

Rituximab has become the mainstay of systemic therapy for patients with follicular lymphoma and is associated with an improved outcome at both diagnosis and relapse, either as induction or maintenance therapy. The challenge lies in maximizing the benefit of this drug in a condition characterized by multiple relapses.

Survival of patients with high-risk early-stage breast cancer has been improved by chemotherapy administration at shorter dose intervals: 'dose-dense' therapy. Validation for this approach is provided by the AGO trial, which demonstrated the biggest survival advantage of any study of dose-dense chemotherapy to date.

The optimal chemotherapy regimen to be used concurrently with thoracic radiation for locally advanced non-small-cell lung cancer remains uncertain. Studies investigating this question are ongoing.

Incorporating hematopoietic growth factors into chemotherapy regimens is a common method for mitigating toxicity of dose-intensive regimens. A clinical trial has shown that G-CSF can counteract acute toxicities, permitting further dose intensification of induction chemotherapy. However, the effects of these strategies on long-term toxicities and overall survival remain undefined.

There has been a growing interest in focal treatment for prostate cancer, although this remains a controversial area. Criticism of focal prostate therapy has been based on the fact that prostate cancer is a multifocal disease. The authors of this Review discuss the clinical and biological implications of multifocal prostate cancer in the context of focal therapy patient selection and treatment planning.

One of the seven ongoing trials of accelerated partial breast irradiation (APBI) has concluded that single-dose intraoperative radiotherapy should be considered as an alternative to protracted whole-breast irradiation. With a median follow up of 2 years, such conclusions seem premature. Until the risk and pattern of breast recurrence is reported at longer follow up, TARGIT APBI should remain an experimental approach.

BRCAmutation carriers have an increased risk of developing breast cancer. Modern technology has made it possible to move genetic screening into the mainstream setting, which is important asBRCA status can influence treatment decisions. The authors of this Review discuss the assessment of familial cancer risk and the criteria for targeting BRCAmutation testing in women with breast cancer. They also examine how this genetic knowledge impacts on optimal patient management.

MicroRNAs (MiRNAs) can act as oncogenes or tumor-suppressor genes and have differential expression in tumor progression and metastasis. MiRNAs are involved in a number of pathways that contribute to metastasis, including migration, invasion, cell proliferation, epithelial-to-mesenchymal transition, angiogenesis and apoptosis. This Review provides a summary of the existing data documenting these functions and describes the clinical utility of miRNAs as prognostic and predictive biomarkers and their potential therapeutic applications in advanced cancer.

The IAEA-ACC study compared accelerated radiotherapy with standard radiotherapy in a multicenter trial conducted in developing countries. Advantages were most notable in patients with early-stage disease, which may limit the utility of this therapy. In countries where resources are limited, however, this strategy may be a cost-effective approach to improving outcomes in patients with head and neck cancer.

Two meta-analyses of the Non Small Cell Lung Cancer Meta-analyses Collaborative Group (NSCLC MACG) on the effects of adjuvant chemotherapy on early stage NSCLC after complete or curative resection have demonstrated that adjuvant cisplatin-based regimens are a valid and recommendable option following curative surgery. We discuss these results in the light of current interdisciplinary guidelines and existing meta-analyses of randomized clinical trials.

Adding lomustine to the standard combination of idarubicin and cytarabine for the treatment of old patients with acute myeloid leukemia improves complete response rates and overall survival. These findings emphasize the importance of dose intensity and raise the question of a unique role for nitrosoureas in the treatment of this disease.

Whether a 70-gene signature could help individualize therapy in breast cancer patients with small tumors is the subject of a recently reported study. The authors of the article raise important issues about how to validate the clinical utility of the new molecular classifiers for risk prediction.