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, the Nobel Laureate in Medicine/Physiology, is continuing his work on the development and preclinical evaluation of peptide analogs with antitumor and additional applications and types of activity at his Endocrine, Polypeptide, and Cancer Institute sited at the Miami Veterans Administration Medical Center and in collaboration with the Clinical Director of Dr. Schally’s Institute, Dr. Norman L. Block.

These antitumor peptides include targeted cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH), AN-152 (AEZS-108) and AEZS-138 (Disorazol-Z-D-Lys-6 LHRH) (so-called “magic bullets”). He has been involved, as well, with the development and clinical therapeutic application of a newly available LHRH antagonist, Degarelix. Dr. Schally produced one of the first commercially available LHRH antagonists, Cetrorelix. This drug is in wide use in the techniques used for in vitro fertilization (IVF) around the world.

In addition to these several analogs and modifications of LHRH, various antagonistic analogs of another neurohormone, growth-hormone-releasing hormone (GHRH) of the Miami series (e.g., MIA-602) have been synthesized here in Miami and evaluated with the goal of selecting the functionally pre-eminent GHRH antagonist for clinical development in cancer therapy. Preclinical evaluation of MIA-602 (large scale synthesis, toxicology, pharmacodynamics, and pharmacokinetics) continues. Plans for Phase I and Phase II clinical trials are being formulated. This program is aimed at providing a theoretical, preclinical, and mechanistic basis for planned clinical trials with 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 is to be placed on the development of effective therapies for relapsed, androgen-independent, prostate cancer, triple-negative breast cancer, and ovarian cancer. Thus, the evaluation of the effects of these analogs on prostate cancers, breast cancers, ovarian cancers, and endometrial cancers is being carried out. These proposed investigations should shed more light on the processes of tumorigenesis and the proliferation of tumors, as well as on the mechanisms of antitumor activity of these analogs. This research is leading to the development of innovative, cost-effective therapies for these malignancies. Of special note is the absence, in comparison to the standard chemotherapy drugs, of significant side effects in the use of these agents. While this may initially appear inconceivable, it is to be considered that the LHRH agonists, developed by Dr. Schally, and currently in use around the world for later stage prostate cancer, also have very minimal inherent side-effects. It is actually the effect of these drugs, the androgen suppression, that has the side-effects, rather than the drugs themselves. As the more anaplastic cancers appear to have a greater expression of the appropriate hormone receptors and, as these receptors appear to be necessary for the mechanisms of action of these drugs, it would imply that the more anaplastic tumors will respond better and with lesser side-effects to these neurohormonal derivatives.

Dr. Schally also continues to spend a portion of his time assisting and advising clinicians in the implementation of the therapeutic methods, developed by him, for treatment of additional, multiple cancers. Dr. Schally is participating in several clinical trials, including a Phase III evaluation of his targeted cytotoxic LH-RH analog, AN-152 (designated commercially as AEZS-108), in women with gynecologic cancers, Phase I/II trials with AEZS-108 in men with prostate cancer, AEZS-108 in patients with bladder cancer and pancreatic ca

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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