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The proto-oncogene c-Myc is deregulated and overexpressed in ~70% of all cancers. Thus, c-Myc is an attractive therapeutic target since disrupting c-Myc activity could be used as pan-chemotherapy. Beyond cancer, Myc is also a positive effector of tissue inflammation, and its function has been implicated in the pathophysiology of heart failure. Because c-Myc is a transcription factor, a rationally designed small molecule targeting c-Myc would be required to exhibit significant specificity.

RNA interference (RNAi) is a naturally occurring post-transcriptional gene regulation process that represses the expression of specific genes. Exploiting endogenous RNAi by externally-delivered small-interfering RNA (siRNA) is a promising therapeutic for the treatment of various diseases representing several major unmet medical needs. 

Mantle cell lymphoma (MCL) is a group of aggressive B-cell lymphomas displaying heterogeneous outcomes after treatment.  Some patients have the slowly progressing disease that does not require immediate treatment, while others have a disease that rapidly progresses despite highly aggressive treatment. A number of prognostic tools have been described to determine whether patients have slow or rapidly progressing diseases, including the mantle cell lymphoma International Prognostic Index (MIPI) and biomarkers, such as KI-67.

Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is essential for regulating DNA damage checkpoints during the cell cycle. ATR, is phosphorylated at threonine 1989 site (T1989) in response to DNA damage and ATR activation leads to activation of downstream substrates, signaling cascades and cell cycle arrest. ATR is a potential target for anticancer therapeutics to induce cancer cell death by inhibiting cell cycle arrest pathways in response to chemotherapeutics.

Diazeniumdiolates comprise a diverse class of NO-releasing compounds and materials that are known to exhibit sufficient stability to be useful as therapeutics.

Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.

Chimeric antigen receptors (CARs) with high affinity for mesothelin that can be used as an immunotherapy to treat cancers that express mesothelin, such as pancreatic cancer, ovarian cancer, and mesothelioma. The technology includes CAR constructs with one of three different mesothelin-specific antibody portions, including either the mouse-derived SS or SS1 antibody fragments or the human HN1 antibody fragment.

Melanoma is a particularly aggressive form of cancer primarily caused by over-exposure to sunlight.  Although melanoma can strike at any age, the malignancy disproportionately impacts persons of advanced age, as these individuals often have decades of repeated exposure to harmful levels of ultraviolet radiation.  Scientists at NIH among others have clarified the link between advanced melanoma and other malignancies and expression of SPANX-B.

One problem with the development of immunotherapy for cancer or other diseases is the inability to stimulate a sufficient immune response in patients to tumor associated antigens. The Linker Adapted for T Cell Signaling molecule (LAT) has been shown to be an important molecule in T cell signaling. The inventions described and claimed in this patent application illustrate a new supportive role for LAT which may be harnessed to improve a patient's immune response to tumor-associated antigens.

The development of more targeted means of treating cancer is vital. One option for a targeted treatment is the creation of a vaccine that induces an immune response only against cancer cells. In this sense, vaccination involves the introduction of a peptide into a patient that causes the formation of antibodies or T cells that recognize the peptide. If the peptide is from a protein found selectively on/in cancer cells, those antibodies or T cells can trigger the death of those cancer cells without harming non-cancer cells. This can result in fewer side effects for the patient.