Review Articles in 2012

Kinesins — a family of molecular motors that travel unidirectionally along microtubule tracks — have emerged as potential targets for cancer drug development. As discussed in this Review, several compounds that inhibit mitotic kinesins have entered clinical trials and others are being developed, raising the possibility that the range of kinesin-based drug targets may expand in the future.

The family of lysyl oxidases (LOX) seem to have dichotomous roles in tumour progression: suppressing tumorigenesis and promoting metastasis. This Review discusses the functions of the LOX family and the rationale for targeting them.

The bromodomain is a highly conserved motif found in proteins that interact with chromatin. Small molecules that inhibit bromodomain and extraterminal (BET) proteins have been described, and this Review examines these developments and discusses the implications for small molecule epigenetic targeting of chromatin networks in cancer.

This Review discusses the links between the E3 ubiquitin ligase COP1 and cancer, as shown by mouse models and human tumour data. It describes the evidence for COP1 targeting both oncoproteins and tumour suppressor proteins for degradation, how these apparently contradictory data might be rectified and the therapeutic implications.

This Review discusses the importance of spatial control of receptor tyrosine kinase (RTK) activity during development and tissue homeostasis, and how spatial deregulation of RTKs may contribute to tumorigenesis and affect the sensitivity and resistance of cancers to pharmacological RTK inhibitors.

Research over the past decade has greatly increased our understanding of non-apoptotic programmed cell death events, such as lysosomal-mediated cell death, necroptosis and cell death with autophagy. This Review discusses converging and diverging features of these pathways with a view to developing new therapeutics for cancer.

Autophagy can have two functions in cancer: it can be tumour suppressive or tumour promoting. Therefore, defining the context-specific role for autophagy in cancer and the mechanisms involved is important for the use of autophagy-based therapeutics.

Populations of tumour cells display remarkable phenotypic diversity as a result of both genetic and non-genetic influences. This Review discusses underlying causes of this intra-tumour phenotypic heterogeneity, and why this phenomenon may affect our ability to diagnose and effectively treat tumours.

This review discusses some of the new insights on the development of multiple myeloma that can be gained from considering the evolution of this disease from a Darwinian perspective.

There are multiple subclasses of melanoma that are partly categorized on the basis of their oncogenic molecular drivers. As discussed in this Review, the understanding of the molecular features of melanoma has led to several exciting advances in the treatment of patients with melanoma.

The development of therapeutic antibodies requires a substantial understanding of cancer serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system and cancer cells. This Review outlines the fundamental strategies required to develop antibody therapies for cancer patients.

Dendritic cells have far-reaching and important effects on the activation of the immune response; thus, they are used to vaccinate patients with cancer to induce long-term anti-tumour immunity. This Review discusses what we know — and need to know — about dendritic cells to improve how they are used therapeutically.

Targeted therapies can be used to successfully treat cancer patients, but what are their mechanisms of action? This Review discusses how targeted therapies modulate the immune system and how they can be rationally combined with immunotherapies.

Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

There are many connections between wound healing and tumorigenesis. Using the epidermis as an example, this Review discusses these connections and how stem cells affect these two processes.

This Review reflects on the recent disappointing initial results from Phase III trials of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, and discusses the next steps in targeting insulin and IGFI signalling in cancer therapy.

Aberrant nuclear morphology is already used as a diagnostic criterion for cancer, but why is the nucleus deformed in cancer cells? This Review discusses how components of the nuclear envelope and the adjoining lamina are deregulated in cancer cells and the consequences of this change in cell morphology.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. This Review discusses the roles of PPARs in cancer and focuses on PPARβ/δ and the controversies yet to be resolved.

Signalling through the receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor (HGF/SF) has been associated with various types of cancer, which has led to numerous efforts to try and target these proteins. This Review discusses HGF/SF–MET signalling in cancer and current progress with targeting this pathway.

Nuclear factor-κB (NF-κB) has many functions in cancer, hence the need for drugs that can modulate its activity. In order to achieve this, Neil D. Perkins argues that the complex roles of the individual NF-κB subunits must be considered.