Articles in 2015

The recently updated breast cancer screening guidelines from the American Cancer Society are less aggressive than previous versions and clearer about overdiagnosis. However, a lack of attention was placed on the differences in effect estimates between trials at high and low risk of bias, and the authors failed to quantify the most serious harm.

Lung-cancer treatment paradigms continue to advance as we exploit our growing understanding of the genetic basis of both tumorigenesis and therapy resistance. Moreover, ongoing developments with targeted therapies are improving patient outcomes, with two new drugs approved in 2015 for non-small-cell lung cancer and many others showing promise.

Advances in key areas of research have enabled improved outcomes for patients diagnosed with ovarian cancer in the past three decades. In 2015, this trend was maintained with important progress in areas such as guideline compliance, design of targeted approaches and molecular profiling.

In 2015, published trials highlighted the remarkable efficacy of docetaxel combined with androgen-deprivation therapy in patients with newly diagnosed metastatic prostate cancer. Also in 2015, a large study revealing potential molecular targets for metastatic castration-resistant prostate cancer therapies was published, along with a study showing activity of PARP inhibition in patients harbouring mutations in genes governing DNA repair.

A meaningful revolution in managing malignant diseases has occurred since the advent of molecular targeted therapies; while some agents have resulted in a clinical benefit, these novel agents are also associated with undesired effects and assessing these risks in the correct context of potential clinical benefit is paramount. The authors overview of the development and toxicity profiles of kinase inhibitors and monoclonal antibodies, with an emphasis on their clinical management, including patient supportive care needs, and the impact of these treatments use on the health-care expenditures at the end of life.

In a little over the past year, several clinical trials have evaluated new drugs in patients with metastatic colorectal cancer and gastric cancer. Furthermore, genomics studies that attempted to unravel the molecular characteristics of colorectal and gastric cancer were published in 2015. The results of these endeavours will influence clinical practice in 2016 and beyond.

Henderson and colleagues previously highlighted the need for more-rigorous standards of preclinical experimental design and reporting metrics. They now build on their earlier work with a meta-analysis of preclinical experiments that examined the efficacy of sunitinib. Their results demonstrate how suboptimal preclinical study designs can prompt unwarranted clinical expectations.

The presence of tumour-infiltrating lymphocytes (TILs) in breast tumours is related to a better prognosis in patients with early stage breast cancer, but the immunobiology of breast cancer remains to be well-characterized. In this Review, the authors discuss how to measure TIL-related parameters in the clinic, as well as their value as a prognostic and predictive biomarker in breast cancer. The rationale for enhancing immunity in breast cancer is also examined.

Acute myeloid leukaemia (AML) is a heterogeneous disease that is typically associated with a very poor prognosis; however, cytogenetic and molecular abnormalities that characterize different forms of AML have been used to better prognosticate patients and inform treatment strategies, which might enable better outcomes to be achieved. Moreover, in the era of next-generation sequencing and molecularly targeted therapy, genetic profiling of patients with AML could open new avenues of treatment. Herein, the authors discuss the evidence-base for integrating mutational data into treatment decisions for patients with AML, and propose novel therapeutic algorithms aimed at improving outcomes of this dismal disease by promoting clinical research.