Release Date: 22-Aug-2023
The use of peptides as therapeutic agents benefited significantly from the discovery of insulin in 1921, which led to further research and development in this field. Since then, peptide applications have been evaluated in a number of indications, including cancer, and several peptide based drugs have received approval in recent years. Many of these peptides based drugs are commercially successful, fueling the creation of further peptide drugs spanning different diseases. Cancer, however, being one attributed to a large number of deaths globally, has been receiving special attention in the past few decades. In the last few years, peptide drugs for cancer have been increasing in number and the large number of candidates under clinical development together suggests a promising future for this new class of drugs.
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Peptide based drugs offer a myriad of opportunities for the treatment of different cancers because of the flexibility they offer in terms of the targets they can address, or the numerous prospects of structural modifications they come with. In addition, the peptide can be developed into druggable forms that are not limited to ingestible pills, such as vaccines. Moreover, they can also be used as combinatorial agents and be used in different cancer treatment regimens with different anticancer drugs. This is also being seen in different clinical trials where different agents are being combined with peptide drugs and vaccines to assert the most optimum effects on cancer patients.
Bristol Myers Squibb, along with the National Cancer Institute and National Institutes of Health, is conducted an early phase clinical trial for its KRAS-targeting peptide vaccine given in combination with the checkpoint inhibitors Nivolumab (anti-PD-1) and Ipilimumab (anti-CTLA-4) in patients with colorectal cancer and pancreatic cancer. KRAS mutations have been associated with poor survival and increased tumor aggressiveness in both colorectal and pancreatic cancers, making it an excellent target for drug development. The peptides can trigger an immune response in these patients, allowing their immune systems to eradicate cancer cells on their own. On the other hand, the immune checkpoint inhibitors can block the cellular signaling facilitating the growth of cells. Therefore, as a combination, the two form one such strategy to kill cancer cells and reduce tumor burden.
With research and development activities for peptide drugs in cancer gaining momentum in the last few years, many new approaches of using peptides for cancer treatment are emerging. The most prominent of these is perhaps the Peptide Receptor Radionuclide Therapy (PRRT), which exploits the targeting ability of peptide to kill cancer cells using a radionuclide. Drugs used in this therapy utilize a peptide bound to a radionuclide, which releases medical radiation toxic to cancer cells. The therapy is currently suggested for the treatment neuroendocrine tumors, and holds potential to be expanded in other conditions.
As an emerging therapeutic field using an equally emerging therapeutic modality, Peptide Receptor Radionuclide Therapy has been receiving attention lately, and some candidates have been successful in making a mark in the market. Lutathera (177Lu-DOTATATE) was the first radiopharmaceutical to receive approval from the FDA and EMA. Another, 177Lu-edotreotide (ITM-11), developed by ITM Radiopharma, received the Fast Track Designation from the US FDA in October 2022 for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 177Lu-edotreotide consists of the radioactive molecule lutetium-177 bound to edotreotide, a synthetic formulation of the peptide hormone somatostatin, and is currently in phase III COMPETE and COMPOSE clinical trials.
A newly published study from researchers at the Memorial Sloan Kettering Cancer Center identified and confirmed the role two biomarkers circulating in the blood as a means of predicting the patient responsiveness to Peptide Receptor Radionuclide Therapy with Lutathera. This is being hailed as a method to foresee treatment outcomes in patients undergoing Lutathera treatment. At present, no biomarkers have been identified that can be used to predict the outcomes of radiopharmaceutical therapy for neuroendocrine tumors, and with the cancer center’s results being the first in this aspect, is expected to transform several aspects related to radiopharmaceutical therapy, including the development of personalized therapies using radiopharmaceutical.
Peptide-based drugs have been used in the treatment of cancers for many years now, but the development and introduction of different drug class has been acting as promising competitors that have been limited the growth and uptake of peptide drugs. Therefore, there is an urgent need to incorporate strategies to improve peptide drugs and show them as a promising therapeutic approach for cancer.