Investigational Oncology Protocol for dogs
Also searched as: triple protocol, TA1 PNC-27 ivermectin
The short answer
Thymosin alpha-1 with PNC-27, sometimes with ivermectin. The most experimental protocol on this site, and the one requiring the most caution.
What it is and why these compounds
This combination pairs thymosin alpha-1 — an immune modulator with strong human safety data and, unusually, no tumour-promotion signal — with PNC-27, a peptide investigated for selectively lysing cells that display membrane HDM-2. Ivermectin is sometimes added for its reported effects on Wnt and Akt/mTOR signalling. It needs stating plainly that PNC-27 has no companion animal data whatsoever: every published finding is cell culture or rodent. This protocol is documented here because owners searching for canine cancer options will encounter it, and an accurate account with its limitations attached is more useful than silence. It has no place outside a veterinary oncology relationship.
Compounds in this protocol
Approved for human use as Zadaxin outside the United States — the strongest evidence base on this site.
A highly experimental oncology peptide with no companion animal data.
A Nobel Prize-winning antiparasitic with published in vitro canine mammary tumour data.
Before starting
These are the decisions that determine whether this protocol is appropriate at all.
⚠ Read first
PNC-27 has no companion animal data of any kind. All published evidence is in vitro or rodent. This is the least evidenced compound on the site.
Caution
MDR1 genetic testing is mandatory before ivermectin. In affected dogs — Collies, Australian Shepherds, Shelties, Old English Sheepdogs, Border Collies and herding mixes — neurotoxicity at these doses can be fatal.
Caution
This protocol should never be run outside a veterinary oncology relationship, and never as a replacement for conventional treatment that has a realistic chance of helping.
Caution
Quality of life, not tumour dimensions, is the endpoint that should govern decisions.
Example timeline
A representative schedule drawn from the published literature, showing what is monitored and when. Any actual protocol should be set by the veterinarian managing the case.
- 1Week 1Staging and immune priming
What owners observe
Begin thymosin alpha-1 alone. Photograph and measure all visible masses. Record appetite, energy, and pain behaviour as a baseline for quality-of-life scoring.
Clinical monitoring
Full staging: imaging, CBC with differential, chemistry panel. MDR1 genetic testing if ivermectin is contemplated. TA1 at 50–100 mcg/kg subcutaneously three times weekly.
- 2Week 2Add PNC-27
What owners observe
Two separate injections on alternating days. Watch for changes in mass size or texture. Maintaining food intake is critical and weight loss should be reported immediately.
Clinical monitoring
Add PNC-27 subcutaneously or intratumorally two to three times weekly. Stagger from TA1 dosing days. Weigh weekly — loss beyond 5% warrants intervention.
- 3Weeks 4–6First assessment
What owners observe
A mass may soften, shrink, or ulcerate. Ulceration reflects necrosis and can indicate response rather than deterioration, but always needs veterinary assessment.
Clinical monitoring
Re-image and compare dimensions. Repeat CBC — lymphocyte counts should be improving if TA1 is having its expected effect. Add ivermectin only if MDR1 testing is clear.
- 4Weeks 8–12+Ongoing assessment
What owners observe
Quality of life governs the decision to continue. Sustained appetite, comfort and engagement are the metrics that matter. Report any sudden decline immediately.
Clinical monitoring
Full restaging at weeks 8 and 12. Monthly liver and kidney values. Continue only while the dog is stable or responding.
Investigated for
Common questions
What is the Investigational Oncology Protocol for dogs?+
Thymosin alpha-1 with PNC-27, sometimes with ivermectin. The most experimental protocol on this site, and the one requiring the most caution. It combines Thymosin Alpha-1, PNC-27, Ivermectin.
Is the Investigational Oncology Protocol safe for dogs?+
PNC-27 has no companion animal data of any kind. All published evidence is in vitro or rodent. This is the least evidenced compound on the site. MDR1 genetic testing is mandatory before ivermectin. In affected dogs — Collies, Australian Shepherds, Shelties, Old English Sheepdogs, Border Collies and herding mixes — neurotoxicity at these doses can be fatal. This protocol should never be run outside a veterinary oncology relationship, and never as a replacement for conventional treatment that has a realistic chance of helping. Quality of life, not tumour dimensions, is the endpoint that should govern decisions.
How long does the Investigational Oncology Protocol run?+
The example timeline runs from week 1 through weeks 8–12+. Actual duration should be set by the veterinarian managing the case and adjusted on response.
References
- 1.King R, Tuthill C Immune Modulation with Thymosin Alpha 1 Treatment. Vitamins and Hormones, 2016. PMID 27450734
- 2.Dominari A, Hathaway Iii D, Pandav K, et al. Thymosin alpha 1: A comprehensive review of the literature. World Journal of Virology, 2020. PMID 33362999
- 3.Wei Y, Zhang J, Yan X, et al. Thymosin α-1 in cancer therapy: Immunoregulation and potential applications. International Immunopharmacology, 2023. PMID 36812669
- 4.Guo Y, Chang H, Li J, et al. Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway. Apoptosis, 2015. PMID 26002438
- 5.Wang F, Yu T, Zheng H, Lao X Thymosin Alpha1-Fc Modulates the Immune System and Down-regulates the Progression of Melanoma and Breast Cancer with a Prolonged Half-life. Scientific Reports, 2018. PMID 30120362
- 6.Sarafraz-Yazdi E, Bowne WB, Adler V, et al. Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes. PNAS, 2010. PMID 20080680
- 7.Sarafraz-Yazdi E, Pincus MR, Michl J PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis. Biomedicines, 2022. PMID 35625682
- 8.Sookraj KA, Bowne WB, Adler V, et al. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemotherapy and Pharmacology, 2010. PMID 20182728
- 9.Davitt K, Babcock BD, Fenelus M, et al. The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells. Annals of Clinical and Laboratory Science, 2014. PMID 25117093
- 10.CANINE STUDYDiao H, Cheng N, Zhao Y, et al. Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling. BMC Veterinary Research, 2019. PMID 31375107
- 11.Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. American Journal of Cancer Research, 2018. PMID 29511601
- 12.Juarez M, Schcolnik-Cabrera A, Dominguez-Gomez G, et al. Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug. Cancer Chemotherapy and Pharmacology, 2020. PMID 32474842
- 13.Tang M, Hu X, Wang Y, et al. Ivermectin, a potential anticancer drug derived from an antiparasitic drug. Pharmacological Research, 2021. PMID 32971268
- 14.Morinaga S, Han Q, Mizuta K, et al. Ivermectin Combined With Recombinant Methioninase (rMETase) Synergistically Eradicates MiaPaCa-2 Pancreatic Cancer Cells. Anticancer Research, 2025. PMID 39740811
Where to source research peptides
Compound quality is the variable most owners underestimate. Purity, accurate peptide content, and correct labelling determine whether any published dosing figure means anything at all. Pet & Peps Research publishes third-party testing on the compounds covered in this guide and supports this site.
Educational information — not veterinary medical advice
Everything on this page is compiled from published peer-reviewed literature for educational and research purposes. It does not establish a veterinarian-client-patient relationship (VCPR) and is not a substitute for veterinary examination and diagnosis. Most compounds described here are investigational or used off-label and are not FDA-approved for these purposes in dogs. Extralabel drug use in animals requires a valid VCPR and the direct supervision of a licensed veterinarian under AMDUCA (21 U.S.C. §360b). Dosing figures are reported as they appear in the source literature and are not recommendations.