The Cancer-Targeting Peptide Library from Phoenix Pharmaceuticals contains a specially curated collection of peptides with cancer promoting or anti-cancer propreties. Each peptide was selected based on published articles, patents, and internal data supporting their role in the cancer pathway. Generally, they can be separated into the following three categories.
(1) Tumor Microenvironment-Associated Peptides (promotors or anticancer): Many signature peptides present in the microenviroment of cancer cells have been identified by mass spectrometry methods. Some of these peptides has been found to influence cancer cell behavior, such as proliferation and metastasis.
(2) Tumor Penetrating Peptides: These peptides are being used for targeted delivery of oligonucleotides, drugs, imaging agents, inorgannic nanoparticles, liposomes, and viruses to cancer cells. Some of these also have secondary anti-cancer properties.
(3) Homing Peptides: These peptides are capable of binding tumor and cancer cells with great specificity. Peptides containing RGD bind to integrins and facilitate cancer cell migration. On the other hand, peptides containing GSL exhibit an inhibition of cancer homing. Some of these peptides also have ability to identify and antagonize or enhance the signal transduction pathways in cancer cells or tissues.Thus, the screening of cancer homing peptides has become an important tool for the effective management of cancer traetment.
Advanced ovarian cancer has been treated in mice by targeting the cancer microenvironment. For example, researchers identified the segment of prosaposin that stimulates thrombospondin-1, creating a modified version of the peptide for use as a potential drug. They found that the modified peptide not only stops the progression of the tumors, but could also shrink tumors to an undetectable state. They tested the peptide in mice with tumors formed by transplanted human ovarian cancer cells.
The below is an example to explore the (a) biological (e.g. integrin binding sites, cell-cell interaction), (B) biophysical (e.g. matrix stiffness properties), and (C) biochemical (e.g. cell-mediated enzymatic degradation) effects using Corning® HTS Transwell®-96 well permeable support.
Example of discovery of anti-angiogenic TSP-1 using peptides/peptidomimetics
Angiogenesis has to be tightly regulated by balancing the production and release of pro- and antiangiogenic molecules. An inbalance in this process contributes to numerous malignant, inflammatory, ischemic, infectious, and immune disorders.
a, Immune cells called T cells that express the proteins CD4 or CD8 on their surface can target and kill tumour cells if they recognize peptides known as antigens (not shown) expressed by the tumour cells. However, this immune response is often suppressed in the microenvironment of a tumour. b, Such immunosuppression can be blocked through treatment that blocks the PD-1-receptor pathway in T cells, enabling them to cause tumour destruction or regression. c, Ott et al. and Sahin et al. report phase I clinical studies that investigated a vaccine-based approach to treat skin cancer. They identified antigens that were expressed on the tumours of individual patients, and generated a personalized vaccine to initiate or strengthen immune responses against these antigens. The authors observed a broadened and boosted immune response against the tumour, with both CD8+ and CD4+ T cells responding to the antigens presented in the vaccine. d, The vaccinations resulted in the destruction or regression of tumours. In some patients, residual tumours could be destroyed by the subsequent use of a treatment to block the PD-1-receptor pathway. It seems probable that vaccination can lead to the destruction of small tumours that have recurred or migrated to other locations in the body (metastases), whereas larger recurrences or metastases might need PD-1-receptor pathway blockade to be completely destroyed.
Tumor-targeting peptide ligands can be conjugated directly or indirectly to functional groups on the outer leaflet of the protocell lipid bilayer. Functionalized protocells can be loaded with a wide variety of cargos such as chemotoxins, genes, siRNA, aptamers or imaging agents. The composition of the lipid bilayer can be modified to regulate the concentration of bound peptide ligands to minimize binding site inhibition and optimize therapeutic indices, and may also incorporate different polymer coatings (purple dots) to improve circulation retention times.
Self-assembling peptides improve the stability of glucagon-like peptide-1 by forming a stable and sustained complex. A complex of Pep-1 and GLP-1 exhibited a remarkable extension in the half-life of GLP-1. In addition, the experimental animals treated with a GLP-1/Pep-1 complex exhibited better blood glucose clearance activity over a greater duration of time than the animals treated with GLP-1 alone. Based on these results, an adjustment of the Pep-1 and GLP-1 ratios is presumed to be able to control the half-life of GLP-1 (e.g., medium-acting and long-acting). The findings in this study also suggest that the self-assembling peptide Pep-1 could serve as a powerful drug preparation tool to extend the short half-life of therapeutic peptides.