Adult human sarcomas. I. Basic science.
When connective tissue undergoes malignant transformation, glioblastomas and sarcomas arise. However, the ancient biochemical mechanisms, which are now operational in sarcomas distorted by mutations and gene fusions in misaligned chromosomes, were originally acquired by those cells that emerged during the Cambrian explosion. Preserved throughout evolution up to the genus Homo, these mechanisms dictate the apoptosis- and senescence-resistant immortality of malignant cells. A 'retroviral paradox' distinguishes human sarcomas from those of the animal world. In contrast to the retrovirally induced sarcomatous transformation of animal (avian, murine, feline and simian) cells, human sarcomas have so far failed to yield a causative retroviral isolate. However, the proto-oncogenes/oncogenes transduced from their host cells by retroviruses of animals are the same that are active in human sarcomas. Since the encoded oncoproteins arise after birth, they are recognized frequently by the immune system of the host. Immune lymphocytes that kill autologous sarcoma cells in vitro commonly fail to do so in vivo. Sarcoma vaccines generate immune T- and natural killer cell reactions; even when vaccinated patients do not show a clinical response, their tumors become more sensitive to chemotherapy. The aim of this review is to lay a solid molecular biological foundation for the conclusion that targeting the sarcoma oncogenes will result in regression of the disease.
Sinkovics
Joseph G
JG
Cancer Institute of St. Joseph's Hospital Affiliated with the HL Moffitt Cancer Center, The University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa, Florida, USA. sinkovi.joseph@baycare.org
D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D006801:Humans; D012509:Sarcoma / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines