Tyrosine kinase inhibitors are taking up an increasingly significant role in treating cancers. There are different types of TKIs currently used in clinical settings. However, TKI-associated limitations such as resistance and adverse effects are frequently reported. In this chapter, we would comprehensively review the clinical efficacy of current TKIs using the currently available clinical trial data. Significant limitations of TKIs on cancer treatment will be further summarized and discussed. The strategies on overcoming the limitations of TKIs to maximize their clinical effectiveness and efficiency, such as complementary use of Chinese medicine or development of novel TKIs, will be proposed. In conclusion, an overall picture of the clinical use and limitation of the current TKIs will be drawn and the prospective development in overcoming the limitations will be discussed. Evaluation of clinical efficacy of TKIs, evaluation of limitations of TKIs, strategies in overcoming the limitations of TKIs, and conclusion (including prospective development of TKIs) are discussed below.
Part of the book: Tyrosine Kinases as Druggable Targets in Cancer
The high incidence of cancer is a global burden. Cancer cells acquire immortality, which results in loss of control in cell proliferation and population expansion. Cancer cells undergo a series of genomic instability, leading to mutated amplification or deletion of certain genes that strictly control the cell fate. Programmed cell death is a mechanism of cell fate control that is aberrantly regulated in cancer cells. Apoptosis is the major form of programmed cell death regulated by both intrinsic and extrinsic pathways. Discovering effective and specific alternative solutions that can reprogram apoptosis in cancer cells is always a challenge. Chinese herbal medicine has captured increasing attention from both researchers and manufacturers, as evidenced by observable curative effects from previous clinical experience. Hence, to clarify and reinforce the understanding of the effect of Chinese medicine on cancer, in this chapter, we will retrospectively review the latest 5 years of literature and summarize the mode of action of Chinese herbal medicine on apoptotic cell death in cancer. Both Chinese medicine-induced intrinsic and extrinsic mechanisms of apoptosis will be discussed, and common compounds from Chinese medicine with druggable potential as novel apoptosis-inducing agents will be highlighted.
Part of the book: Programmed Cell Death
Cancer is one of the most prevalent diseases all over the world with poor prognosis and the development of novel therapeutic strategies is still urgently needed. The large amount of successful experiences in fighting against cancer-like diseases with Chinese medicine has suggested it as a great source of alternative treatments to human cancers. Cancer cells have been shown to own a predominantly unique metabolic phenotype to facilitate their rapid proliferation. Metabolic reprogramming is a remarkable hallmark of cancer and therapies targeting cancer metabolism can be highly specific and effective. Based on the sophisticated study of small molecule metabolites, metabolomics can provide us valuable information on dynamically metabolic responses of living systems to certain environmental condition. In this chapter, we systematically reviewed recent studies on metabolism-targeting anticancer therapies based on metabolomics in terms of glucose, lipid, amino acid, and nucleotide metabolisms and other altered metabolisms, with special emphasis on the potential of metabolic treatment with pure compounds, herb extracts, and formulations from Chinese medicines. The trends of future development of metabolism-targeting anticancer therapies were also discussed. Overall, the elucidation of the underlying molecular mechanism of metabolism-targeting pharmacologic therapies will provide us a new insight to develop novel therapeutics for cancer treatment.
Part of the book: Metabolomics