Scientific Publications that support the use of insulin as a biologic response modifier: off-label use of the drug. Insulin Potentiation Therapy or IPT, IPTLD.

1)Poster Presentation at the Third Annual Comprehensive Cancer Management Conference, Washington, DC June 2000

Primary Breast Conserving Treatment for Breast Cancer Using Biologic Response Modification with Insulin in Combination with Non-Toxic Low-Dose Chemotherapy. Steven G. Ayre, M.D.

2)Insulin Shows Promise

Oncology News, 1991, 17(4):1,7

3) Ayre SG, Perez Garcia y Bellon D, Perez Garcia Jr D.  Neoadjuvant low-dose chemotherapy with insulin in breast carcinomas.  Eur J Cancer. 26:1261-2, 1990

4) Ayre SG, Perez Garcia Y Bellon D, Perez Garcia Jr D.  Insulin potentiation therapy:  a new concept in the management of chronic degenerative disease.  Medical Hypotheses 20:199-210, 1986

5) Lippman ME, Dickson RB, Kasid A, et al.  Autocrine and paracrine growth regulation of human breast cancer.  J Steroid Biochem 24:147-154, 1986

6) Hilf R.  The actions of insulin as a hormonal factor in breast cancer.  In:  Pike MC, Siiteri PK, Welsch CW, eds.  Hormones and Breast Cancer, Cold Spring Harbor Laboratory, 1981, 317-337.

7) Cullen JK, Yee D, Sly WS, et al.  Insulin-like growth factor receptor expression and function in human breast cancer.  Cancer Res 50:48-53, 1990

8) Holdaway IM, Freisen HG.  Hormone binding by human mammary carcinoma.  Cancer Res 37:1946-1952, 1977

9) Papa V,  Pezzino V, Constantino A, et al.  Elevated insulin receptor content in human breast cancer.  J Clin Invest 86:1503-1510, 1990

10) Sporn MB, Todaro GJ.  Autocrine secretion and malignant transformation of cells.  N Engl J Med 308:487-490, 1980

11) Jaques G, Rotsch M, Wegmann C, et al.  Production of immunoreactive insulin-like growth factor 1 and response to exogenous IGF-1 in small cell lung cancer cell lines.  Exp Cell Res 176:336-343, 1988

12) Nakanishi Y, Mulshine JL, Kasprzyk PG, et al.  Insulin-like growth factor-1 can mediate autocrine proliferation of human small cell lung cancer cell lines in vitro.  J Clin Invest 82:354-359, 1988

13) Lee PDK, Rosenfeld RG, Hintz RL, Smith SD.  Characterization of insulin, insulin-like growth factors I and II, and growth hormone receptors on human leukemic lymphoblasts.  J Clin Endocr Metab 62:28-35, 1986

14) Colman PG, Harrison LC.  Structure of insulin/insulin-like growth factor-1 receptors on the insulinoma cell, RIN-m5F.  Biochem Biophys Res Commun 124:657-662, 1984

15) Zapf J, Froesch ER.  Insulin-like growth factors/somatomedins:  structure, secretion, biological actions and physiological role.  Hormone Res 24:121-130, 1986

16) Papa V, Constance CR, Brunetti A, et al.  Progestins increase insulin receptor content and insulin stimulation of growth in human breast carcinomas.  Cancer Res 50:7857-7862, 1990

17) Stewart AJ, Johnson MD, May REB, Westley RB.  Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells.  J Biol Chem 265:21172-21178, 1990

18) Eppenberger U.  New aspects in the molecular growth regulation of mammary tumors.  In:  Eppenberger U, Goldhirsch A, eds.  Recent Results in Cancer Research, Vol. 113:  Endocrine Therapy and Growth Regulation of Breast Cancer.  Berlin-Heidelberg, 1989, 1-3

19) DeLeon DD, Bakker B, WIlson RL, et al.  Demonstration of insulin-like growth factor (IGF-I and IGF-II) receptors and binding protein in human breast cancer cell lines.  Biochem Biophys Res Commun 152:398-405, 1988

20) Karey KP, Sirbasku DA.  Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17B-estradiol.  Cancer Res 48:4083-4092, 1988

21) King GL, Kahn CR, Rechler MM, Nissley SP.  Direct demonstration for separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulin-like growth factor) using antibodies to the insulin receptor.  J Clin Invest 66:130-140, 1980

22) Jacobs S, Cook S, Svoboda M, Van Wyk JJ.  Interaction of the monoclonal antibodies alpha-IR-1 and alpha-IR3 with insulin and somatomedin-C receptors.  Endocrinol 118:223-226, 1986

23) Goustin AS, Leof EB, Shipley GD, Moses HL.  Growth factors and cancer.  Cancer Res 46:1015-1029, 1986

24) Unterburger P, Sinop A, Noder w, et al.  Diabetes  mellitus  and  breast  cancer:  a retrospective follow-up study.  Onkologie 13:17-20, 1990

25) Yee D, Palk S, Lebovic GS, et al. Analysis of insulin-like growth-factor I gene expression: evidence for a paracrine role in human breast cancer. Mol Endocrinol 3:509-517, 1990

26) Hilf R.  Primary and permissive actions of insulin in breast cancer.  In:  Leung BS, ed.  Hormonal regulation of mammary tumors.  Montreal, Eden Press, 1982, Vol. 2, 123-137

27) Alabaster O, Vonderhaar BK, Shafie SM.  Metabolic modification by insulin enhances methotrexate cytotoxicity in MCF-7 human breast cancer cells.  Eur J Cancer Clin Oncol 17:1223-1228, 1981

28) Oster JB, Creasey WA.  Enhancement of cellular uptake of ellipticine by insulin preincubation.  Eur J Cancer Clin Oncol 17:1097-1103, 1981

29) Schilsky RL, Bailey BD, Chabner BA.  Characteristics of membrane transport of methotrexate by cultured human breast cancer cells.  Biochem Pharmacol 30:1537-1542, 1981

30) Shinitzky M, Henkart P.  Fluidity of cell membranes – current concepts and trends.  Int Rev Cytol 60:121-147, 1971

31) Jeffcoat R.  The biosynthesis of unsaturated fatty acids and its control in mammalian liver.  Essays Biochem 15:1-36, 1979

32) Gasparro FP, Knobler RM, Yemul SS, Bisaccia E, Edelson RL.  Receptor mediated photo-cytotoxicity:  synthesis of a photoactivatable psoralen derivative conjugated to insulin.  Biochem Biophys Res Comm 141:502-209, 1986

33) Poznansky MJ, Singh R, Singh B.  Insulin:  carrier potential for enzyme and drug therapy.  Science 223:1304-1306, 1984

34) Ayre SG.  New approaches to the delivery of drugs to the brain.  Med Hypotheses 29:283-291, 1989

35) Gross GE, Boldt DH, Osborne CK.  Perturbation by insulin of human breast cancer cell kinetics.  Cancer Res 44:3570-3575, 1984

36) Paridaens R, Klijn JGM, Julien JP, et al.  Chemotherapy with estrogenic recruitment in breast cancer:  experimental background and clinical studies conducted by the EORTC breast cancer cooperative group.  Eur J Cancer Clin Oncol 22:728, 1986

37) Van der Burg B, de Laat SW, van Zoelen EJJ.  Mitogenic stimulation of human breast cancer cells in a growth-factor defined medium:  synergistic action of insulin and estrogens.  In:  Brescani F, King RGB, Lippman ME, Raynaud JP, eds.  Progress in Cancer Research and Therapy, vol. 35:  Hormones and Cancer 3.  New York, Raven Press, Ltd.  1988, 231-233.

38) Goldfine ID, Purello F, Vigneri R, and Clawson GA.  Direct regulation of nuclear functions by insulin:  relationship to mRNA metabolism.  In:  Czech MP, ed. Molecular Basic of Insulin Action.  New York, Plenum Press, 1985, 329-345.

39)Blood Brain Barrier Passage of Azidothyumidine in Rats: Effects of Insulin

Steven G. Ayre (1), Brian Skaletski (2) and Aron D. Mosnaim( 2). 

Research Communications in Chemical Pathology and Pharmacology JANUARY 1989 VOL.63, NO. 1. Departments of Family Medicine and Pharmacology and Molecular Biology , University of Health Sciences/The Chicago Medical School, North Chicago, IL 60064.

40)New Approaches to Delivery of Drugs to the Brain. S.G. Ayre. Medical Hypotheses 29:283-291, 1989

41)Insulin, chemotherapy, and the mechanisms of malignancy: the design and the demise of cancer. S.G. Ayre, M.D., D. P. Garcia Bellon, M.D., D. P. Garcia, Jr., M.D. Medical hypotheses 55.4 (2000): 330-334.

42)Low dose chemotherapy in combination with insulin for the treatment of metastatic tumors: C. Damyanov, M. Radoslavova, V. Gavrilov, D. Stoeva. Medical Center of Integrative Medicine, Sofia, Bulgaria. Journal of BUON 14: 711-15, 2009.

43)Insulin Potentiation Therapy in the treatment of malignant neoplastic diseases: a three year study. Damyanov C, Gherasimova DM, Avramov LA, Masley IK (2012). J Cancer Sci Ther 4: 088-091. doi:10.4172/1948-5956.1000117

44)Low-Dose Chemotherapy with insulin (Insulin Potentiation Therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer. Damyanov, Christo, et al. ISRN urology 2012 (2012).

45)Metabolic Modification by Insulin Enhances Methotrexate Cytotoxicity in MCF-7 Human Breast Cells. Alabaster, O. Vonderhaar, B. and Shafie, S. Eur J Cancer Clin Oncol. Vol 17, No. 11, pp 1223-1228. 1961. 

46)Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Lundholm K, Körner U, Gunnebo L, Sixt-Ammilon P, Fouladiun M, Daneryd P, Bosaeus I. Clin Cancer Res. 2007 May 1;13(9):2699 706.

47)Long-Term Effect of Diabetes and Its Treatment on Cognitive Function. Jacobson, Alan, et.al. N Engl J Med 2007; 356:1842-52.

48)Preclinical safety and antitumor efficacy of insulin combined with irradiation. Bénédicte F. Jordan, Nelson Beghein, Nathalie Crokart, Christine Baudelet, Vincent Gregoire, Bernard Gallez. Radiotherapy and Oncology 81 (2006) 112–117.

49)Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients. Lasalvio-Prisco, Eduardo, et.al. Cancer Chemother Pharmacol (2004) 53: 220–224.

50)The effect of insulin on chemotherapeutic drug sensitivity in human esophageal and lung cancer cells. Zhonghua Yi Xue Za Zhi. 2003 Feb 10;83(3):195-7. 

51)Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells. Zou K, Ju JH, Xie H. Acta Pharmacol Sin. 2007 May; 28(5):721-30. 

52)A pilot study of Auron Misheil Therapy (AMT) in patients with advanced cervical cancer: tumor response and its correlation with clinical benefit response, and preliminary quality of life data.” Scheele, Jürgen, et al. Oncology reports 22.4 (2009): 877-883.

53)Insulin in endometrial carcinoma chemotherapy: A beneficial addition and not a problem. Sha, Huilan, et al. Journal of Huazhong University of Science and Technology [Medical Sciences] 30 (2010): 631-637.

54) Insulin for Everything. TIME magazine April 10, 1944

55)Long-Term Outcomes of the Treatment of Unresectable (Stage III - IV)Ductal Pancreatic Adenocarcinoma Using Metabolically Supported Chemotherapy (MSCT): A Retrospective Study

Mehmet Salih Iyikesici1, Ayshe Slocum2*, Engin Turkmen3, Ovunc Akdemir4, Abdul Kadir Slocum5, Turgut Ipek6, Erhun Eyuboglu6, Ferhan Bulent Berkarda7

56)Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer. Mehmet Salih İyikesici, Abdul Kadir Slocum, Ayshe Slocum, Ferhan Bulent Berkarda, Miriam Kalamian, andThomas N Seyfried. Cureus. 2017 Jul; 9(7): e1445.Published online 2017 Jul 7. doi:  10.7759/cureus.1445. PMCID: PMC5589510. Monitoring Editor: Alexander Muacevic and John R Adler

57)Integrative Oncology at the Clinicist's Look. Chronology for the Creation and Development of the IPT & BMP Method for Treatment of Oncological Diseases. It is uploaded on the following link: http://www.clinicsinoncology.com/pdfs_folder/cio-v4-id1671.pdf . 

58)The Impact of Insulin on Low-dose Metronomic Vinorelbine and Mafosfamide in Breast Cancer Cells

Published Feb 28, 2021 · S. Krajnak, Amelie Loewe, M. Battista+5 more. https://ar.iiarjournals.org/content/anticanres/41/3/1243.full.pdf

59)Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality

Published Aug 31, 2019 · P. Ramteke, Ankita Deb, Varsha Shepal+1 more .https://mdpi-res.com/d_attachment/cancers/cancers-11-01402/article_deploy/cancers-11-01402-v2.pdf?version=1568975785

60)Insulin enhancement of the antitumor activity of chemotherapeutic agents in colorectal cancer is linked with downregulating PIK3CA and GRB2

Published Nov 11, 2019 · Siddarth Agrawal, M. Woźniak, M. Łuc+8 more. https://www.nature.com/articles/s41598-019-53145-x

61)Palliative treatment efficacy of glucose inhibition combined with chemotherapy for non-small cell lung cancer with widespread bone and brain metastases: A case report.

Published Nov 30, 2017 · Yongping Liu, Ya-ping Zhang, X. Mao+5 more. https://www.spandidos-publications.com/10.3892/br.2017.1008/download

62)Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme

Published Jan 18, 2014 · C. Champ, J. Palmer, J. Volek+6 more. https://link.springer.com/article/10.1007/s11060-014-1362-0

Survivor for 12 years: My life, Alexandrina a cancer survivor and cancer free after 12 years. May 16,2025. Thank you Dr. Donato.

I have survived for 12 years as of May 16, 2025

The day:
May 16, 2025
In the photo (Published with permit from Ale & Nelly):
Alexandrina Lara (a patient who has survived for over 12 years), Dr. Donato, and Mrs. Nelly Cordova (Alexandrina's mother).

The story in the photo:

It began over 12 years ago when Alexandrina was diagnosed by a doctor in Los Angeles, California, USA, with a cancerous tumor in her right mammary gland. With that tremendous scare, Mrs. Nelly, Ale's mother, remembered that in 1977, her father, Benjamin Cordova Gonzalez, was treated at Dr. Donato Perez Garcia's Clinic in Mexico City by my father, Dr. Donato Perez Garcia y Bellon. Mr. Benjamin had been diagnosed with a cancerous tumor in his prostate, and on the recommendation of another relative, he did not have surgery and received the drug therapy invented by my grandfather Donato in 1930. The result was that Mr. Benjamin did not have prostate surgery, he responded to the treatment, his cancerous tumor went into complete remission, and he lived to be 90 years old and cancer-free. This is why Alexandrina has been a cancerous tumor survivor for 12 years who received my drug therapy, is in complete remission, has no traces of tumors, and her blood tests are within the normal range. This day, May 17, 2025, Alexandrina attended her annual maintenance consultation and treatment under my supervision.

In the Infusion Room, she shared her experience with Vanessa, who is 32 years old, lives in Canada, and was diagnosed with a cancerous tumor of the mammary gland in 2022, and with Kylee, who is 37 years old, lives in Utah, and was diagnosed with an ovarian tumor. Both were given at their local Hospitals invasive, very aggressive treatments that caused low white blood cell, red blood cell, and low platelet counts, and they didn't improve. So, after listening to Dr. Lodi's podcast and talking with him, they both decided to start my therapy. This Friday, they heard the reality of what my therapy can do. Alexandrina told them, and what better example than she's alive and has overcome cancer for more than 12 years. Incredible, but it's a real-life reality. Of course, like Alexandrina, there are several of my patients with similar stories who have survived for more than 34 years.

It is my hope that this letter will give encouragement to and instill confidence in anyone considering IPT as a treatment.

Why do patients come to Mexico (Tijuana, Baja California) seeking complementary therapies and a treatment alternative?

Because patients want to be treated with functional medicine so their disease can be effectively treated and, like Alexandrina, they can recover and become cancer survivors (for more than 12 years). They come to me because I offer experience, a treatment alternative discovered in 1930 by my grandfather, which is effective in most cases, and, above all, the survival rate is very good. Clinica Dres. Donato Perez Garcia (Established 1930).