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Cancer immunotherapy approaches, such as adoptive cell transfer (ACT), proved effective against many cancer types. Yet, post-treatment analyses of ACT have suggested that efficacy may be enhanced by increasing the percentage of neoantigen-reactive T cells in the infused product. Neoantigens are new proteins that form on cancer cells when certain mutations occur in tumor DNA. Current techniques for identifying neoantigen-specific TCRs in T cell expression are labor-intensive, time-consuming and technically challenging.

There is no known cure for Alzheimer’s disease, a brain disorder that severely affects memory, thinking, learning, and organizing skills. It eventually decreases a person’s ability to carry out simple, daily activities. It is predicted that over 14 million Americans will develop Alzheimer’s without effective treatment options. Mild cognitive impairment (MCI) is a stage prior to Alzheimer’s when memory problems become noticeable. A patient’s ability to function and live independently remain intact as the brain compensates for disease-related changes.

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.

The Transforming Growth Factor Beta (TGF-ß) ligands (i.e., TGF-ß1, -ß2, -ß3) are key regulatory proteins in animal physiology. Disruption of normal TGF-ß signaling is associated with many diseases from cancer to fibrosis. In mice and humans, TGF-ß activates TGF-ß receptors (e.g., TGFBR1), which activates SMAD proteins that alter gene expression and contribute to tumorigenesis.  Reliable animal models are essential for the study of TGF-ß signaling.

Cytokines are a broad category of intercellular signaling proteins that are critical for intercellular communication in human health and disease. However, systematic profiling of cytokine signaling activities has remained challenging due to the short half-lives of cytokines, and the pleiotropic functions and redundancy of cytokine activities within specific cellular contexts.

The use of tumor transcriptomics for precision oncology has made significant advances, mainly by identifying cancer driver genes or actionable mutations for treatment with targeted therapies.  However, this strategy misses out on broader genetic interactions that could reveal additional biologically testable biomarkers for therapy response prediction and inform the selection of more effective drugs for targeted treatment.

The development of precision medicine approaches for DLBCL (Diffuse Large B Cell Lymphoma) is complicated by its genetic, phenotypic and clinical heterogeneity. Current classification methods do not fully explain the observed differences in clinical outcomes to current chemotherapy and targeted therapy. Therefore, better analytical methods to classify and predict DLBCL patients’ treatment response are needed.

The tumor microenvironment (TME) is a complex mixture of cell types whose interactions affect tumor growth and clinical outcome. Recent studies using fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (RNAseq) to elucidate tissue composition and cell-cell interactions in the TME led to improved biomarkers of patient response and new treatment opportunities. However, the use of FACS is limited to simultaneously measuring the expression of a few protein markers, whereas the use of single-cell RNAseq has been limited due to cost and scarcity of fresh tumor biopsies.

Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors such as camptothecin, rinotecan, and topotecan are widely used anti-cancer agents that work by stabilizing the TOP1-DNA cleavage complex.

Antiretroviral therapy (ART) has changed the prognosis of HIV-1 infection to a chronic illness that, in most cases, can be managed or controlled. Integrase strand transfer inhibitors (INSTIs) and reverse transcription inhibitors are essential components of ART drug cocktails. In compliant individuals, ART has been found to block viral replication completely. Additionally, blocking viral replication can prevent the emergence of drug resistance.