title: AKT as Locus of Cancer Unknown Primary Site.
abstract: Cancer of unknown primary site is a metastasis developed by the positive feedback loops of primary cancer forming extreme cancer robustness. Such robustness occurs only in metastatic cancer or in relapsed lymphoma, myeloma, plasmocytoma, or leukemia. However, when it develops in primary cancer, hypoxic microenvironment generates positive feedback loops which hyperactivate AKT locus, forming extreme robustness that forcing cancer cells to migrate to the distant site, but primary cancer loosing that property or remains silent. Positive loops are the force and principal mechanism of metastasis development. A cancer cell is converted normal cell. Conversion occurs at the AKT genomic locus. Thus, cancer is genomic disease rather than disease of the specific organs. Targeting such locus by the locus chemotherapy (redox balance change) rather than by organ specific therapy results in conversion of positive loops into negative and disappearance of extreme robustness and malignant phenotype of the cancer unknown primary origin.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Radisavljevic
mesh_terms: D002465:Cell Movement; D025461:Feedback, Physiological; D006801:Humans; D008954:Models, Biological; D009382:Neoplasms, Unknown Primary / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D051057:Proto-Oncogene Proteins c-akt
keywords: AKT LOCUS; CANCER OF UNKNOWN ORIGIN; EXTREME ROBUSTNESS; POSITIVE FEEDBACK LOOPS