Volume 11 Issue 2, February 2014

In 2013, the treatment of several NSCLC subtypes was refined. PROFILE-1007 and LUX-Lung 3 confirmed that targeted therapy was superior to chemotherapy, whereas NCIC BR19 and PointBreak failed to show superiority of adjuvant gefitinib and combined maintenance therapy, respectively. These studies reinforced some practices and discouraged others, underscoring the need for new prospective studies.

2013 saw much progress in breast cancer research. Advances in high-throughput technologies continue to refine our knowledge of the molecular biology of breast cancer, and are beginning to give insight into cancer evolution, drug resistance, and how to deploy precision therapeutics.

Next-generation sequencing analysis and characterization of the microenvironment 'field-effect' that promotes hepatocellular carcinoma (HCC) development has revealed critical players and potential targets for chemoprevention. A biomarker-based drug development strategy is needed to improve future HCC clinical trials and therapies.

In 2013, new insights on the molecular features of cutaneous melanoma provided a paradigm shift in our understanding of the biology of this disease. Exploiting immune checkpoint blockade and the use of BRAF-targeted or MAPK-targeted agents contributed to important progress in the treatment and management of cutaneous melanoma.

In 2013, studies confirmed that HPV infection of target cells predisposes to cervical (pre)cancer. In developed countries, HPV screening revealed superior protection than cytology screening. In India, visual inspection of the cervix after acetic acid application significantly reduced cervical cancer mortality after 12 years. Improved survival for women with advanced disease was observed after adjuvant bevacizumab.

The year 2013 has brought more options for patients with metastatic colorectal cancer (mCRC) with new ways to combine traditional agents, further refinement of predictive molecular for EGFR inhibitors and a new salvage option. Molecular profiling could identify subgroups to further improve treatment selection.

Many targeted anticancer treatments may benefit only a subgroup of the histologically-defined population and thus may be missed by traditional randomized clinical trial designs that focus on the overall treatment effect. New biomarker driven designs can help to identify subgroups of patients who are most likely to benefit from these treatments. In this Review the authors discuss how to select appropriate designs and analysis strategies for phase III, biomarker driven clinical trials, using specific examples to illustrate their advantages (and disadvantages).

Novel approaches for cancer therapy take advantage of the modulation of the immune system. Immunotherapy is however associated with a number of adverse effects and clinicians will need to become familiar with recognizing and managing them. In this Review the authors describes the toxicity profiles for various anticancer therapies based on immunomodulatory agents.

Is there such a thing as a 'good death'? Palliative care services alleviate the debilitating physical symptoms and psychological distress that patients with cancer frequently experience at the end of their lives. In this Review, Khan and colleagues discuss the preferences of these patients and how advance care planning can help in meeting these choices.

In this Review, Jeff Shrager and Marty Tenenbaum describe the latest generation of Precision Oncology, and the different ways to keep refining it. In Precision Oncology 3.0, each treatment event provides the chance to learn from it so that such treatment can be applied to other patients with similar characteristics without facing the difficult economic and structural challenges of a clinical trial.