Volume 14 Issue 1, January 2017

Molecular cancer-classifier assays enable the diagnosis of a single cancer type for most patients with cancer of unknown primary (CUP), thus opening the door to the administration of site-specific therapies. Herein, I discuss how such therapies can improve the survival of patients with CUP, and the resulting paradigm shift towards tissue-of-origin diagnostics and treatments that is now becoming the standard of care for this patient population.

Active surveillance has been proposed as a management option that reduces the risk of overtreatment in patients diagnosed with early stage prostate cancer. However, up until now, this approach has not been tested in a prospective, randomized fashion. The PROTECT study confirms that patients diagnosed with prostate cancer through prostate-specific antigen (PSA)-based screening are at a very low risk of cancer-related mortality, but patients undergoing active surveillance do have an increased risk of disease progression and metastases compared with those managed with upfront therapy.

The VOICE study addressed the oncologist–patient dyad by adding a two-sided intervention. The results of this ostensibly positive study are, at best, limited and, at worst, cosmetic because clinically relevant long-term outcomes were unaffected. VOICE is the first attempt at addressing complexity in this genre of studies and, even with its shortcomings, teaches us some important lessons.

Metabolic reprogramming to support tumour growth is a near universal characteristic of cancer, and thus targeting cancer metabolism has been, and continues to be, a focus for drug-development efforts. In this Review, the authors describe the various metabolic alterations and vulnerabilities of tumours that are potentially important targets for anticancer agents, highlighting both the challenges and opportunities.

Distant metastasis remains a common cause of death in patients with solid tumours, even after treatment with surgery, radiotherapy and/or chemotherapy. Treatment itself can sometimes cause or promote metastasis by increasing the number of circulating tumour cells. The authors of this article discuss preclinical and clinical data concerning cancer treatments, circulating tumour cell mobilization and other factors that might promote metastasis.

Patients diagnosed with cancer through an emergency presentation have worse outcomes compared with those in whom cancer is diagnosed through other routes; therefore, reducing the number of patients presenting as an emergency with cancer will improve patients' outcomes. In this Review, the authors describe the available evidence in this area, and provide recommendations for future research, clinical practice and public health policy.

The presence ofde novoresistance or the development of acquired resistance in cancer cells has limited the use of targeted agents. Combinations of targeted treatments can circumvent some mechanisms of resistance to yield clinical benefit. The authors explore the challenges in identifying the best drug combinations and the best combination strategies, as well as the complexities of delivering these treatments to patients.