It is well known that the occurrence and development of cancer involves a series of complex molecular genetic variations, including mutations, deletions, deactivations that affect genes involved in cell differentiation, regulation of cell proliferation and epigenetic modification (Ferrara, Lancet, 2013. 381 (9865): 484-95; Ghaneh, Gut, 2007. 56 (8): 1134-52). Due to the high complexity of genetic variations, the development of therapeutic drugs targeting these variations is highly challenging. Recent studies have shown that metabolic reprogramming is a hallmark of malignant tumors (Hanahan, Cell, 2011. 144 (5): 646-74.). Metabolism also plays a very important role in the development and progression of the tumor (Wang, Cell, 2014. 158 (6): 1309-23; Chen, Blood, 2014. 124 (10): 1645-54. In the network structure of the biological system, the metabolic network is located downstream of the genetic network, and much less complex than the genetic network (Chen, Cancer Cell, 2016. 30 (5): 779-791). Thus, the development of therapies specifically targeting disordered metabolic pathways of cancer cells can be less challenging and more achievable. It is known that the glycolytic pathway of malignant tumor cells are extremely active in order to support the synthesis of large amounts of precursors and ATPs required for rapid cell proliferation. As a result, the glycolytic pathway has become a hot target for the development of new anticancer drugs. Acute myeloid leukemia (AML) is a lethal blood malignancy and the most common acute leukemia affecting adults and its incidence increases with age. The treatment of AML is mainly based on cytarabine and (demethoxy) daunorubicin as chemotherapy. After a standardized treatment, the 5-year survival rate for these patients is only 30% (Chen, Blood, 2014.124 (10): 1645-54.). Pancreatic cancer is among the most deadly and aggressive of all cancers. By the time that pancreatic cancer is diagnosed, many people already have disease that has spread to distant sites in the body (about 53%). The treatment options include surgery and radiotherapy/chemotherapy. Pancreatic cancer is also relatively resistant to medical treatment, and common chemotherapeutic agents for the treatment of pancreatic cancer include 5-fluorouracil (5-FU), gemcitabine, gemcitabine, capecitabine, paclitaxel and cisplatin. The 5-year survival rate for pancreatic cancer patients is still less than 5% due to the extremely low response rate to chemotherapy (Berardi, J Gastroint Dig Syst, 2013. 3 (134): 2.). It is noteworthy that the above-mentioned chemotherapeutic drugs for AML and pancreatic cancer are non-targeted, killing normal cells while killing tumor cells, thus giving patients strong side effects, including severe bone marrow suppression, neurotoxicity and heart toxicity and so on. Therefore, the development of high efficiency and specificity new anti-cancer drugs, as well as efficient chemotherapy sensitizing agents, is the focus of many investigations.
The present invention provides a treatment which can be used for AML and pancreatic cancer and cancer having similar metabolic characteristics, and is targeted and has minimal influence on normal cells in view of the above deficiencies.
USPTO Backgrounds
USPTO Backgrounds