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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

Steroid hormones have been implicated to play a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes, or hormones involved in androgen regulatory pathway, reportedly influence risk for developing prostate cancer. Since many membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival.

Medical image datasets are an important clinical resource. Effectively referencing patient images against similar related images and case histories can inform and produce better treatment outcomes. Labeling and identifying disease features and relations between images within a large image database has not been a task capable of automation. Rather, it is a task that must be performed by highly trained clinicians who can identify and label the medically meaningful image features.

Adoptive cell transfer (ACT) uses tumor infiltrating lymphocytes (TILs) that recognize unique antigens expressed by cancer cells (“neoantigens”). Neoantigen specific TIL administration in patients has resulted in long term regression of certain metastatic cancers. However, one of the challenges of ACT and engineered T cell receptor (TCR) therapies more broadly, is the identification and isolation of these mutation specific TILs and TCRs. Only a fraction of TILs in a given patient is known to be tumor reactive, while the majority are not useful for cell therapy.

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.

High expression of CD47, a cell surface receptor on several types of cancer cells, has been identified as a ‘don’t eat me signal’ that inhibits their killing by macrophages or NK cells. Conversely, the CD47 antibody B6H12 that blocks SIRPα binding enhances macrophage-dependent clearance of tumors in several mouse models, although others have shown that such clearance can be independent of SIRPα signaling.

It is well known that overactive Ras signaling is linked to many forms of cancer, and despite intensive efforts worldwide to develop effective inhibitors of Ras, to date there is no anti-Ras inhibitor in clinical use.

Medical imaging is an important resource for early diagnostic, detection, and effective treatment of cancers. However, the screening and review processes for radiologists have been shown to overlook a certain percentage of potentially cancerous image features. Such review errors may result in misdiagnosis and failure to identify tumors. These errors result from human fallibility, fatigue, and from the complexity of visual search required.

One form of adoptive T cell therapy (ACT) consists of harvesting tumor infiltrating lymphocytes (TIL), screening and isolating TIL which display tumor antigen-specific T-cell receptors (TCR), expanding the isolated T cells in vitro, and reinfusing them into the patient for treatment. While highly active in the treatment of certain cancers (e.g., melanoma), current methods used to produce cancer-reactive T cells require significant time and may not adequately identify the desired TCRs which bind cancer targets.