Although chemotherapy has advanced into the era of targeted drugs, the antitumor efficacies of current therapies are limited, most likely because of the high degree of cancer clonal heterogeneity, intratumor genetic heterogeneity and cell signal complexity. As shutdown of a single target does not necessarily eradicate the cancer, the use of combinations of molecular-targeted agents (MATs) has been proposed, and some pioneering research has been conducted to examine the efficacy of this strategy. In this article, the clinical and preclinical studies that are underway in an attempt to improve the anticancer efficacy of chemotherapies through combination strategies are summarized. Studies of combining cytotoxic agents with MATs, coinhibiting two or more targets in a single pathway or coinhibiting parallel or compensatory pathways as well as specific combinations will be introduced, and the antitumor potentials of each combination strategy will be evaluated.

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples. The resulting 820 nonredundant sequences were analysed by high throughput bioinformatics analysis. Human proteins were identified for 73% (596) of the DD sequences. A large proportion (>50%) of the remaining unassigned sequences match ESTs (expressed sequence tags) from human tumours. For the functionally annotated proteins, there is significant enrichment for relevant biological processes, including cell motility, protein biosynthesis, stress and immune responses, cell death, cell cycle, cell proliferation and/or maintenance and transport. Three of the novel proteins (TMEM16A, PHLDB2 and ARH-GAP21) were analysed further to show that they have the potential to be developed as therapeutic targets.