Sylvester Comprehensive Cancer Center

Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c.

Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c.

Nobel Laureate, and Professor of Pathology

Description of Research

Dr. Andrew V. 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), AN-152 (AEZS-108), LHRH antagonist Degarelix, and various antagonistic analogs of growth-hormone-releasing hormone (GHRH) of Miami series e.g., MIA-602 synthesized and evaluated with the aim of selecting a GHRH antagonist for clinical development. Preclinical evaluation of MIA-602 including large scale synthesis, toxicology and pharmacokinetics continues. Plans for Phase I clinical trials are being formulated. This program is aimed at providing a theoretical, preclinical, and mechanistic basis for planned clinical trials with these peptide analogs in various cancers, including prostatic, pancreatic, gastric, colorectal, malignant brain tumors, small cell lung cancer and non-small cell lung cancer, bladder cancer, renal and thyroid cancer, 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 being studied. The results obtained in collaboration with the University of Shantou, China, from a cohort of 982 patients and based on evaluation of GHRH receptors expression by immunohistochemistry indicate that upregulation of GHRH receptors is positively correlated with the progression of gastric cancer and is associated with poor prognosis of patients. GHRH receptor is a novel independent biomarker for prognosis of gastric cancer patients. GHRH antagonist MIA602 demonstrated excellent therapeutic potential against gastric cancer. Recently Dr. Schally’s lab showed the presence of GHRH receptors in 3 human acute myeloid leukemia cell lines (K-562, THP-1 and KG-1a) and demonstrated that GHRH antagonist MIA 602 inhibits growth of these cell lines in vitro and in vivo after xenografting into nude mice. These findings offer a new therapeutic approach to this malignancy. 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 participated in various clinical trials, including Phase II evaluation of targeted cytotoxic LH-RH analog AEZS-108 in women with gynecologic cancers, Phase I/II trials in men with prostate cancer, and 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.

Highlights

  • Dr. Schally was awarded the Nobel Prize in Medicine/Physiology in 1977 for his work on proving the existence of several hypothalamic hormones.
  • 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 presence of receptors for growth hormone-releasing hormone (GHRH) on tumors.
  • Developed antagonists of GHRH for treatment of various cancers.
  • Recently Dr. Schally was named an Inaugural Fellow of the AACR Academy (American Association for Cancer Research) for his contributions to cancer therapy.
  • He was also named a “Legend in Urology” by the Canadian Urological Association and the Canadian Journal of Urology.

Selected Cancer-Related Publications

  • Rick FG, Abi-Chaker A, Szalontay L, Perez R, Jaszberenyi M, Jayakumar AR, Shamaladevi N, Szepeshazi K, Vidaurre I, Halmos G, Krishan A, Block NL, Schally AV. Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist. Proc Natl Acad Sci U S A 110:2617-22,2013 Read more »
  • Rick FG, Block NL, Schally AV. Agonists of luteinizing hormone-releasing hormone in prostate cancer. Expert Opin Pharmacother :,2013 Read more »
  • Jaszberenyi M, Schally AV, Block NL, Nadji M, Vidaurre I, Szalontay L, Rick FG. Inhibition of U-87 MG glioblastoma by AN-152 (AEZS-108),a targeted cytotoxic analog of luteinizing hormone-releasing hormone. Oncotarget 4:422-32,2013 Read more »
  • Jaszberenyi M, Schally AV, Block NL, Zarandi M, Cai RZ, Vidaurre I, Szalontay L, Jayakumar AR, Rick FG. Suppression of the proliferation of human U-87 MG glioblastoma cells by new antagonists of growth hormone-releasing hormone in vivo and in vitro. Target Oncol :,2013 Read more »
  • Perez R, Schally AV, Vidaurre I, Rincon R, Block NL, Rick FG. Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers. Oncotarget 3:988-97,2012 Read more »
  • Dioufa N, Farmaki E, Schally AV, Kiaris H, Vlahodimitropoulos D, Papavassiliou AG, Kittas C, Block NL, Chatzistamou I. Growth Hormone-Releasing Hormone Receptor Splice Variant 1 is Frequently Expressed in Oral Squamous Cell Carcinomas. Horm Cancer 3:172-80,2012 Read more »
  • Klukovits A, Schally AV, Szalontay L, Vidaurre I, Papadia A, Zarandi M, Varga JL, Block NL, Halmos G. Novel antagonists of growth hormone-releasing hormone inhibit growth and vascularization of human experimental ovarian cancers. Cancer 118:670-80,2012 Read more »
  • Muñoz-Moreno L, Arenas MI, Schally AV, Fernández-Martínez AB, Zarka E, González-Santander M, Carmena MJ, Vacas E, Prieto JC, Bajo AM. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer. Int J Cancer :,2012 Read more »
  • Papadia A, Schally AV, Halmos G, Varga JL, Seitz S, Buchholz S, Rick F, Zarandi M, Bellyei S, Treszl A, Szalontay L, Lucci JA. Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer. Horm Metab Res 43:816-20,2011 Read more »
  • Pozsgai E, Schally AV, Hocsak E, Zarandi M, Rick F, Bellyei S. The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines. Int J Oncol 39:1025-32,2011 Read more »
  • Pozsgai E, Schally AV, Zarandi M, Varga JL, Vidaurre I, Bellyei S. The effect of GHRH antagonists on human glioblastomas and their mechanism of action. Int J Cancer 127:2313-2322,2010 Read more »
  • Pozsgai E, Schally AV, Halmos G, Rick F, Bellyei S. The Inhibitory Effect of a Novel Cytotoxic Somatostatin Analogue AN-162 on Experimental Glioblastoma. Horm Metab Res 42:781-786,2010 Read more »
  • Hohla F, Buchholz S, Schally AV, Krishan A, Rick FG, Szalontay L, Papadia A, Halmos G, Koster F, Aigner E, Datz C, Seitz S. Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells. Cancer Lett 294:35-42,2010 Read more »
  • Chen SH, Lin CY, Lee LT, Chang GD, Lee PP, Hung CC, Kao WT, Tsai PH, Schally AV, Hwang JJ, Lee MT. Up-regulation of fibronectin and tissue transglutaminase promotes cell invasion involving increased association with integrin and MMP expression in A431 cells. Anticancer Res 30:4177-86,2010 Read more »
  • Emons G, Kaufmann M, Gorchev G, Tsekova V, Gründker C, Günthert AR, Hanker LC, Velikova M, Sindermann H, Engel J, Schally AV. Dose escalation and pharmacokinetic study of AEZS-108 (AN-152),an LHRH agonist linked to doxorubicin,in women with LHRH receptor-positive tumors. Gynecol Oncol 119:457-61,2010 Read more »
  • Kovács M, Schally AV, Hohla F, Rick FG, Pozsgai E, Szalontay L, Varga JL, Zarándi M. A correlation of endocrine and anticancer effects of some antagonists of GHRH. Peptides 31:1839-46,2010 Read more »
  • Liu SV, Schally AV, Hawes D, Xiong S, Fazli L, Gleave M, Cai J, Groshen S, Brands F, Engel J, Pinski J. Expression of Receptors for Luteinizing Hormone-Releasing Hormone (LH-RH) in Prostate Cancers following Therapy with LH-RH Agonists. Clin Cancer Res 16:4675-4680,2010 [JIF 6.747] Read more »

Programs

Collaborating in the Multidisciplinary Research Program(s):

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