Retinoic acid and interferon in human cancer: mechanistic and clinical studies.
Various combinations of retinoids, metabolic and synthetic derivatives of vitamin A, and interferons (IFNs) have demonstrated synergistic antiproliferative, differentiating, and antiangiogenic activity in some human hematologic and solid-tumor systems. This synergistic antitumor activity may be due to enhanced gene expression. In several cell systems, the actions of IFNs are enhanced by differentiation of cells with retinoic acid (RA). Combined RA-IFN effects have been correlated with the induction of higher levels of IFN-stimulated genes than the levels induced by either agent alone. Natural and synthetic retinoids have been found to augment the antiproliferative activity of IFNs in several squamous cell carcinoma (SCC) and breast tumor cell lines. Results of recent clinical trials indicate substantial activity of 13-cis-RA (13cRA) combined with IFN against advanced SCC of the skin and cervix, and possibly against other solid tumors. Two phase II trials have confirmed activity against locally advanced SCC of the cervix. Successful integration of this regimen with radiotherapy appears to be the most probable means of optimizing clinical outcome. Further studies are needed to determine the mechanistic details of the RA-IFN interaction.
University of Texas M.D. Anderson Cancer Center, Houston 77030.
D M
DM
Moore
D V
DV
Kalvakolanu
S M
SM
Lippman
J J
JJ
Kavanagh
W K
WK
Hong
E C
EC
Borden
M
M
Paredes-Espinoza
I H
IH
Krakoff
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D004357:Drug Synergism; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D015474:Isotretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D011494:Protein Kinases / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D016898:Interferon-alpha; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase; D015474:Isotretinoin