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Several malignancies associated with a poor prognosis such as lung, pancreatic and colorectal cancers frequently harbor constitutively active KRAS mutants, which play a pivotal role in oncogenesis.  Currently, there are no potentially curative treatments against most mutant KRAS harboring cancers once they become metastatic and unresectable.  Despite intensive efforts to develop potent mutant KRAS inhibitors, none have shown a significant improvement to patients.

The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers.  The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.

A child's growth is dependent on the proper functioning of the growth plate, a specialized cartilage structure located at the ends of long bones and within the vertebrae. The primary function of the growth plate is to generate new cartilage, which is then converted into bone tissue and results in the lengthening of bones. Failure of the growth plate to function properly can result in short stature or sometimes a skeletal dysplasia, such as achondroplasia, in which the bones are not just short but also malformed.

One major challenge in the development of effective cancer therapies is a lack of universal, cancer specific markers in target cells. The current standard therapies rely on surgery, chemotherapy, and radiation therapy. Such procedures lead to a population of resistant cancer cells that makes further applications of chemotherapy/radiation therapy ineffective. Additionally, the systemic application of chemotherapy lacks specificity and has  off-target systemic effects that lead to adverse side effects.

Scientists at NIH have identified a process to select highly tumor-reactive T cells from a patient tumor sample based on the expression of four specific T cell surface markers: programmed cell death protein 1 (PD-1; CD279), 4-1BB (CD137), T cell lg-and mucin-domain-containing molecule-3 (TIM-3), and/or lymphocyte activation gene 3 (LAG-3). After this enriched population of tumor fighting T cells, primarily tumor infiltrating lymphocytes (TIL), is selected and expanded to large quantities, it gets re-infused into the patient via an adoptive cell transfer (ACT) regimen.

Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes.  NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability.  For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments. 

 A number of factors can play a detrimental role in the process of wound healing such as poor nutritional status, smoking, various drugs, cancer, and diabetes.  Wound healing impairment is a challenging clinical problem with no efficacious treatments currently available.  Nitric oxide (NO) has been shown to play a role in the process of wound healing by promoting both the proliferative and remodeling phases of healing. 

Aberrant function of the WNT-b-catenin pathway is a common underlying cause of tumorigenesis.  Despite the attractiveness of the WNT-b-catenin pathway as a therapeutic target, WNT dependent cell signaling is also crucial for normal tissue development, and is ubiquitous in all organs.  As a result, WNT-b-catenin pathway inhibitors cause many side effects and fail to meet FDA safety standards.  A more targeted approach is needed to develop safe and effective WNT signaling inhibitors.

The National Cancer Institute, Cancer and Inflammation Program seeks parties interested in collaborative research to further co-develop inhibitors of STAT proteins for the treatment of cancer.

Thalidomide and its close analogs (lenalidomide and pomalidomide) are widely used to treat a variety of diseases, such as multiple myeloma and other cancers as well as the symptoms of several inflammatory disorders. However, thalidomide is known for its teratogenic adverse effects when first clinically introduced in the 1950s, and is associated with drowsiness and peripheral neuropathy. Hence, there is intense interest to synthesize, identify and develop safer analogs.