Human Solid Cancer Decoded

The secret of human solid tumors was largely concealed by a chicken-egg paradox. Common solid tumors are initiated in tumor microenvironment, and from rare mutant stem cells. A cancer-initiating gene is the only specific marker to reveal mutant cell lineages in tumor stroma, and these cell lineages are required for analysis to reveal the cancer-initiating gene. For decades, it is hard for scientists to find one without first finding the other. Two major types of mutant cell lineages are now revealed. They are mutant immune cells when tumors have chronic inflammation, and mutant blood vessel pericytes when tumors have angiogenesis, often both concurrently present in solid tumors. A DNA repair factor GT198 (gene symbol PSMC3IP) is a specific marker of mutant pericyte stem cells and their decedent lineages in solid tumors. Supporting to this concept, here we find that GT198 is a direct protein target of existing anticancer chemotherapy drugs including doxorubicin, paclitaxel, and etoposide. Importantly, GT198 is also a high affinity target of two herbal medicines known to be clinical effective. Therefore, common solid tumors could be systematically treated with low toxic and high efficacy natural herbs. A unified theory of cancer reconciling historical controversies in cancer research is discussed. New methods in cancer early diagnosis and drug development are outlined.