by Prof. Li Qinxi, Jia Zhang, and others.
Given that: (i) each year nearly 14 million people globally are diagnosed with cancer, and a little more than half of them will die; (ii) cancer deaths globally are expected to be doubled by 2030; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system; (ii) a cheaper alternative to the existing expensive anticancer drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and prevent metastatic progression and relapse of cancers.
Prof. Li Qinsi's research team has recently shown that oncoprotein c-Src: (1) phosphorylates the rate-limiting enzyme of the glycolysis Hexokinase-1/2 (HK1)/(HK2) at Tyr732; (2) prevents HK dimer formation; (3) increases affinity (decreases Km value for glucose) for glucose; and (4) promotes tumor survival even under poor glucose conditions. Further, they have shown that HK1-Y732 phosphorylation level correlates with metastasis capability of primary cancers. Together, these findings suggest that inhibition of c-Src and its downstream target Hexokinase expression in cancer cells may prevent tumour growth.
This study suggests combinatorial therapy for metastatic cancers. A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263, by increasing the expression of its target genes, it may decrease the expression of c-Src and HK-1/2 (fig. 1). Thereby, it may: (i) augment HK dimer formation; (ii) increase Km value for glucose; (iii) decrease tumor survival; (iv) inhibit tumor proliferation and growth; and (v) promote tumor regression (fig.1).
Thus, pharmacological formulations encompassing "Metformin and Navitoclax/ABT-263 or its anologs, either alone or in combination with other known anticancer drugs," (fig. 1) may be used to inhibit metastatic progression of primary cancers.
Figure 2. A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN) functions as a potent anti-cancer/metastasis agent.
Undisclosed mechanistic information: How does a pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN) decrease the expression of c-Src and HK1/2?