Transient blockage of proliferative signalling: a novel strategy for protective chemotherapy.
An intact proliferative signalling pathway is essential to the growth of all normal cells, but is often not required by tumor cells. This fact was used to devise a protective chemotherapeutic protocol potentially applicable to all tissues. Four treatments were chosen to temporarily disrupt proliferative signalling. They acted either upstream, at, or downstream of cellular ras activity. As expected, the cell cycle progression of normal cells was temporarily interrupted, while those cells transformed by tumor genes, or tumor cells themselves often were not affected. During these cell cycle blocking treatments the cells were exposed to the topoisomerase inhibitor m-AMSA. This anti-cancer drug is selectively toxic to cycling cells. In each case the tumor cells were selectively killed as judged either by their ability to incorporate labeled thymidine, replate, or grow. These studies suggest new ways to utilize current drugs or search for new ones.
Weyman
C M
CM
Department of Cell Biology, Cleveland Clinic Foundation, OH 44195, USA.
Stacey
D W
DW
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects; D000677:Amsacrine / Q000627:therapeutic use; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008907:Mink; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D011454:Prostaglandins A / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology
D016588:Anticarcinogenic Agents; D011454:Prostaglandins A; D016212:Transforming Growth Factor beta; D000677:Amsacrine; C100008:prostaglandin A2