Peptides are molecules consisting of various chains of amino acids joined by peptide bonds through the process of a dehydration-condensation reaction. There are various places, or various origins of peptides, including but not limited to direct synthesis by the body, artificial synthesis, or through processes such as proteolysis. They play a huge role in the treatment of a variety of diseases, and they are currently at the center stage in the development of various types of vaccines.
Diseases such as allergic reactions, asthma, fibrosis, autoimmune diseases, and infectious diseases have been some of the greatest beneficiaries of peptide-based therapies. There are several advantages that make peptide therapies preferred in the treatment of a variety of diseases. Some of these benefits include the fact that they are easily available, easy to purify and store. Some of the therapies have undergone both in vitro and in vivo testing, with a lot of promising outcomes. There are also several studies continuing to look into how peptides can be used as effective therapies for a variety of conditions.
Apart from being used in search of remedies for normal diseases, peptides also play a vital role in the treatment and management of cancer, including early diagnosis of cancerous cells before they become malignant. Unlike other therapies, peptide-based therapies for cancer have demonstrated great superiority because of their specificity. As a result, peptide-based therapies, as well as peptide-based vaccines, continue to get increased attention from the medical world.
Ever since the approval of sipuleucel-T by the US Food and Drug Administration as the very first standard peptide vaccine for prostate tumors, the number of clinical trials for other types of diseases has heightened. Currently, there is a lot of research for peptide vaccines for diseases such as gastric cancer, breast cancer, colorectal cancer, and melanoma, amongst others. However, it is regrettable to observe that most of the clinical trials are still very limited, and the observed results have also shown very little efficacy.
In this piece, we provide an overview of the new progress that has been made in the application of peptides to various cancer diagnoses, prognosis predictors, and peptide therapies. We will also gloss over the prognosis as well as the adverse effects that peptide vaccines have on various clinical trials.
Peptide Therapies and Colorectal Cancer
Colorectal Cancer – CRC, is one of the leading forms of cancer in the world today. It is believed that nearly a million people die of this type of cancer every year. Those diagnosed with metastatic CRC have a survival rate of fewer than five years and as such, early diagnosis is always seen as one of the best ways to offer a better prognosis.
Currently, peptides play a vital role in the diagnosis of colorectal cancer. For example, FITC-labelled peptides have been linked to cationic CPAA, leading to the formation of CPAA-783-EPPT1. This compound has demonstrated the ability to cell transmembrane MUC-1 proteins into the cell linings of the colorectal.
Additionally, recent clinical studies using human neutrophil peptides 1 – 3 were discovered to be present in colorectals at high concentrations, especially during the Duke stages C and D. Also, another study by Comstock et al. observed a high concentration of serum C-peptide which signified a high risk of adenoma in men. These findings give clear indications that peptides can be used as biomarkers in the detection of colorectal cancer.
In addition to using peptides to detect colorectal cancer, several studies have suggested that they can also be used in the treatment of the disease. One of the peptides, which have been marked as a potential candidate for this is an atrial natriuretic peptide – ANP. It is a vascular and cardiac derived peptide hormone that has been clearly marked as a potential drug for treating colorectal cancer. The reason for this, is that the peptide has shown anti proliferative effects on colorectal cancer cells.
For tumors to grow, there has to be neovascularization, making neovasculature, an attractive target for a plethora of anti-cancer therapies. In a study conducted by Li et al. involving a peptide known as TCP-1, it was observed that the peptide could easily target the blood vessels that supplied blood to the tumor tissues. The study also observed that TCP-1 could be used to deliver fluorescein, as well as drugs for imaging detection and apoptosis in patients suffering from colorectal cancer.
These findings strongly suggest that this particular peptide can be an ideal candidate for CRC therapies due to its ability to carry anticancer drugs to the tissues affected by colorectal cancer and without binding to any of the normal tissues. Additionally, another study reported that F56 peptides have the ability to target both primary lesions and the neovasculature of lung metastases. This could effectively lead to the apoptosis of the necrosis and the neovasculature of the colorectal cancer tissues.
Peptide therapies and lung cancer
Lung cancer is the leading cause of cancer deaths in the world. It has a five-year survival rate, which is still not considered low enough even with the new therapies currently available. Early detection of lung cancer can lead to a better prognosis, and due to the high mortality rates of the disease a lot of attention has been directed at early detection. Several years have passed since a peptide was used in the detection of lung cancer.
Recently, more peptides have been discovered to have the ability to help in the detection of lung cancer. In a study conducted by Wang et al. it was reported that linear peptide antigen obtained from annexin A1 was found to be present in higher amounts in patients suffering from non-small cell lung cancer – NSCLC. The study also discovered a higher concentration of C-peptide in patients suffering from lung cancer, especially those who were in the Stage III-IV group and in patients who suffered from both lung cancer and diabetes.
In another study conducted by McGuire et al, a total of 11 novel peptides known to specifically bind to a series of NSCLC cell linings in humans were discovered in patients suffering from lung cancer. These peptides are also known to be involved with a variety of pathways, giving a clear indication that they can be used in the prediction and early detection of lung cancer. It is also interesting to note that peptides can also be used as carriers. This is due to their ability to bind to specific sites.
In a study involving vasopressin peptide conjugated with 99mTc, it was revealed that the peptide can be used as an ideal compound in the process of imaging small cell lung cancer – SCLC cells. This peptide demonstrated high stability and novel binding to the SCLC cell linings.
Additionally, another study showed that the peptides which bind to progastrin-releasing peptides demonstrated high levels of selective uptake by tumorous tissues. At the same time, it was observed that this peptide had a very low intake in the normal tissues. This was another indication that the peptide could be used effectively for radioimmuno imaging of the SCLC cells.
Several studies have also shown that peptides can be used to treat lung cancer. In a study conducted by Takahashi et al. it was observed that dendritic cell vaccines when conjugated with Wilm’s tumor-1 peptide had the potential of improving the survival rate of patients suffering from advanced NSCLC. Recently, in a study conducted by Ahsa et al. it was observed that synthesized peptide Disruptin had the ability to potentially decrease the clonogenicity of cancer cells dependent on EGFR. The study also showed that Disruptin has the ability to lower or inhibit the density of the microvessels in the linings of the lung cancer cells.
Peptide therapies and gastric cancer
The death rates due to gastric cancer has fallen significantly in the past decade, but the war is not yet over. The cases of gastric cancer have gone down significantly due to improved hygiene leading to low infections by H. pylori, reduced smoking rates, and popularization of refrigeration.
Peptides can be used effectively for detecting and diagnosing gastric cancer. In a study conducted by Zheng et al., it was observed that leucine-rich repeat-containing G protein was significantly high in gastric cancer tissues and as such, it could be used as an early diagnostic biomarker for this type of cancer. Additionally, the use of serum pepsinogen I, pepsinogen II, and carbohydrate antigen 2 have also proven to be effective in the early detection of gastric cancer.
In recent clinical trials involving patients suffering from gastric cancer, peptide-based vaccines were administered, including vaccines with vascular endothelial growth factor receptor-2, lymphocyte antigen 6 complex, and VEGF. It was observed that the administered peptide vaccines were effective in stopping tumor angiogenesis in patients suffering from gastric cancer. The studies also showed improved clinical efficacy of the vaccines, with no severe side effects being recorded in gastric cancer patients.