There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy.

Aberrant histone lysine methylation that is controlled by histone lysine methyltransferases (KMTs) and demethylases (KDMs) plays significant roles in carcinogenesis. Infections by tumor viruses or parasites and exposures to chemical carcinogens can modify the process of histone lysine methylation. Many KMTs and KDMs contribute to malignant transformation by regulating the expression of human telomerase reverse transcriptase (hTERT), forming a fused gene, interacting with proto-oncogenes or being up-regulated in cancer cells. In addition, histone lysine methylation participates in tumor suppressor gene inactivation during the early stages of carcinogenesis by regulating DNA methylation and/or by other DNA methylation independent mechanisms. Furthermore, recent genetic discoveries of many mutations in KMTs and KDMs in various types of cancers highlight their numerous roles in carcinogenesis and provide rare opportunities for selective and tumor-specific targeting of these enzymes. The study on global histone lysine methylation levels may also offer specific biomarkers for cancer detection, diagnosis and prognosis, as well as for genotoxic and non-genotoxic carcinogenic exposures and risk assessment. This review summarizes the role of histone lysine methylation in the process of cellular transformation and carcinogenesis, genetic alterations of KMTs and KDMs in different cancers and recent progress in discovery of small molecule inhibitors of these enzymes.

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through “proteolysis targeting chimera” (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.