Margaret Tyson is an honorary researcher at the Institute of Cancer Sciences, The University of Manchester and runs Manchester Amputee Fitnesss Initiative and Karen's Page

The figures have been formulated using information gained from many different studies, the references for which are listed at the end of the figures and in the text. Activating oncogenic (cancer causing) gene mutations are shown in red and inactivating tumour suppressor gene mutations are shown in yellow. The effects of metformin on the different stages of the pathways are shown by arrows. The "up" arrows indicate activation, the"down" arrows indicate inhibition.

mTOR (mammalian target of Rapamycin) activation leads to cellular proliferation thus cancer. There are two complexes making up mTOR - mTORC1 and mTORC2.

Fig 1 shows the complex pathways involved in mTOR inhibition from the inhibitory effects of metformin on oxidative phosphorylation (respiration) through AMPK dependent pathways and AMPK independent pathways. Fig 1 also connects to other pathways involved in cancer.

AMPK activation can also be achieved through calorific restriction and exercise which are both important in cancer prevention and shown in Fig 1.


Fig 2 follows on from Fig 1 and shows the inhibitory effects of metformin on the oncogene/protein RAS (small GTPase) and pathways leading from RAS to other oncogenic processes.

Fig 3 shows the pathways from the oncogenic serine/threonine protein kinase AKT to other oncogenic processes such as the inflammatory pathway involving the positive feedback loop which includes the inflammatory cytokine Interleukin 6 (IL-6) which is inhibited by metformin.

Fig 4 demonstrates the pathways leading to the most researched and possibly most important mTOR complex from a carcinogenic perspective, mTORC1 and the inhibitory effects of metformin.