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Hydrogels represent an attractive controlled drug-delivery system that have been used in various clinical applications, such as: tissue engineering for wound healing, surgical procedures, pain management, cardiology, and oncology. High-water content of hydrogels confers tissue-like physical properties and the crosslinked fibrillar network enables encapsulation of labile small molecule drugs, peptides, proteins, nucleic acids, proteins, nanoparticles, or cells.

Early detection of liver cancer, such as hepatocellular carcinoma (HCC), is key to improve cancer-related mortality. More than 800,000 people are diagnosed with this cancer each year throughout the world. Liver cancer is also a leading cause of cancer deaths worldwide, accounting for more than 700,000 deaths each year. Currently, millions of Americans and possibly billions in the world are considered at risk for developing liver cancer.

Epidermal growth factor receptor (EGFR) is a transmembrane protein involved in cell growth and proliferation. Mutations in this protein can lead to overexpression, causing several types of cancer; notably, non-small cell lung cancer (NSCLC). For example, mutations in EGFR are found in up to 50% of NSCLC patients and the E746-A750 deletion accounts for 30-40% of such EGFR mutations. Currently, there are no available therapeutics that specifically target the E746-A750 deletion. 

T cell receptors (TCRs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response and destroy abnormal cells. TCRs consist of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit recognition signals by interacting with other proteins. When a TCR is stimulated by an antigen, such as a tumor antigen, some signaling pathways activated in the cell lead to the production of cytokines, which mediate the immune response.

Hematopoietic progenitor cells (HPC) are multi-potent hematopoietic lineage cells that can differentiate into any type of blood cell, including but not limited to erythrocytes, T cells, B cells, and natural killer cells. As such, they have high therapeutic potential in the fields of regenerative medicine and cancer immunotherapy, especially when generated from patient-derived induced pluripotent stem cells (iPSC). Currently, the most efficient protocol to produce HPCs is co-culturing human iPSCs (hiPSC) with mouse stromal cells as a two-dimensional (2D) monolayer.

Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL), T cell receptor (TCR) and Chimeric Antigen Receptor (CAR) engineered T cells, or hematopoietic stem cell transplantation, is a promising new approach to cancer treatment. ACT harnesses an individual's adaptive immune system to fight against cancer, with fewer side-effects and more specific anti-tumor activity. Despite their promise of ACT as curative, these therapies are often limited by the persistence and robustness of the responses of the T cells to the cancer cells.

Pancreatic ductal adenocarcinoma (PDA) accounts for more than 90% of pancreatic cancer cases, and it is one of the most aggressive malignancies with a 5-year survival rate of 6%. The high mortality rate caused by PDA is primarily from the lack of early diagnosis – it is often asymptomatic in early stages – and a poor response to conventional chemotherapy and radiotherapy. One of the major immune cell types present in the PDA microenvironment is a subset of macrophages commonly termed tumor-associated macrophages (TAM).

Chemotherapy resistance in a wide array of cancers is often associated with enhanced glucose uptake and dysregulation of the insulin signaling pathway.  Therapeutics capable of inhibiting insulin signaling would be valuable as a stand-alone treatment and for sensitizing resistant tumors to standard chemotherapy regiments.  Researchers at NCI’s Genitourinary Malignancies Branch have synthesized and developed a series of Englerin-A ana

Due to the large degree of homology among dopamine D2-like receptors, discovering ligands capable of discriminating between the D2, D3, and D4 receptor subtypes remains a significant challenge. The development of subtype-selective pharmaceutical small molecules to activate (agonists) signals regulated by D2-like receptors has been especially difficult. 

Many chemotherapeutic agents cause significant cytotoxicity to non-cancer ("normal") cells, resulting in undesirable side-effects and often limiting the dose and/or duration of chemotherapy that can be administered to a patient.