Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c.
Nobel Laureate, and Professor of Pathology
Description of Research
Dr. Schally, a Nobel Laureate in Medicine, is continuing his work on the development and preclinical evaluation of peptide analogs with antitumor activity. The antitumor peptides include targeted cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH), somatostatin, and bombesin (the so-called “magic bullets”) and LHRH antagonist Cetrorelix. Various antagonistic analogs of growth-hormone-releasing hormone (GHRH) were synthesized and evaluated with the aim of selecting a GHRH antagonist for clinical development. This program is aimed at providing a theoretical, preclinical, and mechanistic basis for planned clinical trials with the peptide analogs in various cancers, including prostatic, pancreatic, gastric, colorectal, malignant brain tumors, lung (small cell lung cancer and non-small cell lung cancer), bladder cancer, renal, and osteosarcomas, melanomas, hepatocellular carcinoma, and lymphomas. The main emphasis will be placed on the development of an effective therapy for relapsed androgen-independent prostate cancer. The evaluation of the effects of various analogs on breast cancers, ovarian cancers, and endometrial cancers is also carried out. These proposed investigations should shed more light on the processes of tumorigenesis and the proliferation of tumors, as well as on the mechanism of antitumor activity of these analogs. This research could lead to the development of innovative, cost-effective therapies for these malignancies. Dr. Schally will continue to spend a portion of his time helping clinicians in the implementation of therapeutic methods developed by him for treatment of various cancers. Dr. Schally participates in various clinical trials, including Phase II evaluation of targeted cytotoxic LH-RH analog AEZS-108 in women with gynecologic cancers, and Phase II/II trials with AEZS-108 in men with prostate cancer and AEZS-108 in patients with bladder cancer. Overall, this program has the potential to make a significant impact on the improvements of therapeutic methods and the delivery of care to the patients afflicted with various cancers.
Dr. Schally was awarded the Nobel Prize in Medicine in 1977 for his work on hypothalamic hormones. The following are highlights/discoveries of his career.
- Discovered hypothalamic hormones TRH, LHRH, and somatostatin
- Developed agonistic and antagonistic analogs of LHRH
- Developed the present therapy for men with advanced hormone-dependent prostate cancer based on LHRH agonists
- Discovered a beneficial effect of LHRH antagonist Cetrorelix in the treatment of men with BPH
- Developed targeted cytotoxic peptide analogs of LHRH, bombesin, and somatostatin
- Discovered the receptors for growth hormone-releasing hormone (GHRH) on tumors
- Developed antagonists of GHRH for treatment of various cancers
Selected Cancer-Related Publications
- Telegdy G, Tanaka M, Schally AV. Effects of the LHRH antagonist Cetrorelix on the brain function in mice. Neuropeptides 43:229-34, 2009. Read more »
- Fu L, Osuga Y, Yano T, Takemura Y, Morimoto C, Hirota Y, Schally AV, Taketani Y. Expression and possible implication of growth hormone-releasing hormone receptor splice variant 1 in endometriosis. Fertil Steril 92:47-53, 2009. Read more »
- Köster F, Engel JB, Schally AV, Hönig A, Schröer A, Seitz S, Hohla F, Ortmann O, Diedrich K, Buchholz S. Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition. Breast Cancer Res Treat 116:273-9, 2009. Read more »
- Theophanous E, Petraki C, Scorilas A, Komborozos V, Veloudis G, Varga JL, Zarandi M, Schally AV, Koutsilieris M. The immunohistochemical expression of growth hormone-releasing hormone receptor splice variant 1 is a favorable prognostic marker in colorectal cancer. Mol Med 15:242-7, 2009. Read more »
- Treszl A, Schally AV, Seitz S, Szalontay L, Rick FG, Szepeshazi K, Halmos G. Inhibition of human non-small cell lung cancers with a targeted cytotoxic somatostatin analog,AN-162. Peptides 30:1643-50,2009. Read more »
- Buchholz S, Seitz S, Schally AV, Engel JB, Rick FG, Szalontay L, Hohla F, Krishan A, Papadia A, Gaiser T, Brockhoff G, Ortmann O, Diedrich K, Köster F. Triple-negative breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH) and respond to LHRH antagonist Cetrorelix with growth inhibition. Int J Oncol 35:789-96,2009. Read more »
- Hohla F, Buchholz S, Schally AV, Seitz S, Rick FG, Szalontay L, Varga JL, Zarandi M, Halmos G, Vidaurre I, Krishan A, Kurtoglu M, Chandna S, Aigner E, Datz C. GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and apoptosis in human colon cancer cells. Cell Cycle 8:3149-56,2009. Read more »
- Laklai H, Laval S, Dumartin L, Rochaix P, Hagedorn M, Bikfalvi A, Le Guellec S, Delisle MB, Schally AV, Susini C, Pyronnet S, Bousquet C. Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer. Proc Natl Acad Sci U S A 106:17769-74,2009. Read more »
- Valdehita A, Bajo AM, Schally AV, Varga JL, Carmena MJ, Prieto JC. Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells. Mol Cell Endocrinol 302:41-8, 2009. Read more »
- Seitz S, Schally AV, Treszl A, Papadia A, Rick F, Szalontay L, Szepeshazi K, Ortmann O, Halmos G, Hohla F, Buchholz S. Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog,AN-162 (AEZS-124), and its effects on tumor growth inhibition. Anticancer Drugs 20:553-8, 2009. Read more »
Collaborating in the Multidisciplinary Research Program(s):