Volume 12 Issue 8, August 2015

The efficacy of immunotherapy in metastatic melanoma is established, with anti-CTLA-4 and anti-PD-1 antibody-based therapies providing unexpectedly high responses and prolonged survival. The combination of nivolumab and ipilimumab is now poised to become the new standard of care, based on a 61% response rate in a recent randomized extended phase I/II trial, confirmed by phase III data presented at ASCO 2015.

The results of the ENESTg1 trial confirm the efficacy of imatinib, but not nilotinib, as a first-line treatment for gastrointestinal stromal tumours (GISTs) harbouring sensitizing mutations in KIT or PDGFRA. Nilotonib might prove to be beneficial in other subset of patients; however, there remains an urgent unmet need to address the GIST subtypes that are therapeutic orphans.

Pancreatic cancer remains a difficult-to-treat malignancy, yet nab-paclitaxel plus gemcitabine prolongs survival. Closer examination of the mechanism of action of nab-paclitaxel hints at a role for targeting KRAS. We discuss how nab-paclitaxel may be active in pancreatic cancer and how this informs the way forward to better treat patients with pancreatic cancer.

Cancer stem cell (CSC) populations are increasingly recognized in most malignancies and are hypothesized to contribute to cancer proliferation, relapse, and metastasis. Thus, the highly conserved stem-cell signal transduction pathways involved in development and tissue homeostasis that are frequently active in CSCs represent prime targets for targeted therapies against this characteristically treatment-resistant and highly tumorigenic cell population. This Review provides a update on the clinical development of therapies targeting Wnt, Notch, and Hedgehog, three prominent stem-cell signalling pathways that are upregulated in CSCs.

Adolescent or young adult (AYA) patients with cancer are a unique group, with unique clinical needs; these patients are not entirely suited to cancer treatment and managment strategies designed either for paediatric patients, or older adult patients. In this Review, issues associated with the treatment, management and long-term outcomes of AYA patients with cancer are described in the context of acute lymphoblastic leukaemia and melanoma.

Transarterial therapies in the setting of primary and secondary liver malignancies are an essential part of the oncology landscape. Most patients are not amenable to curative surgical intervention, which necessitates the use of alternative treatments that preserve quality of life whilst providing clinical benefit. The authors of this Review discuss intra-arterial techniques in light of the current levels of evidence to support their appropriate use in various clinical settings.

Currently, most novel chemotherapies are initially tested in tumour cell lines and xenografts, which generally fail to reflect the full spectrum of tumour-specific mutations, and might explain the low success rates of experimental treatments. In this Perspectives, the mouse hospital co-clinical trial project is described, which enables treatments to be tested in mouse models that accurately reflect the tumour characteristics of individual patients.