Somatic mutations in the additional sex comb-like 1 (ASXL1) gene have been identified in multiple hematologic malignancies, including acute myeloid leukemia (AML), and are associated with poor prognoses1. ASXL1 encodes a nuclear protein that regulates epigenetic remodeling and transcription through interactions with polycomb complex proteins and transcriptional activators and repressors. Several ASXL1 mutations have been associated with loss of protein expression that leads to myeloid transformation2. In contrast, gain-of-function mutations in ASXL1 result in expression of a truncated ASXL1 protein that can bind to BRCA-1 associated protein 1 (BAP1) and cause leukemogenesis3,4. Targeted reduction of BAP1 activity is sufficient to prevent this malignancy process5.
Tumor infiltrating lymphocyte (TIL)-based immunotherapy is currently at the forefront of cutting-edge immuno-oncology treatments. TILs are a type of adoptive cellular therapy (ACT) using lymphocytes that are found within tumor tissues; most of these lymphocytes are T cells that can specifically target tumor cells. For TIL-based therapies, these T cells are harvested from a tumor biopsy, expanded ex vivo, and infused back into the patient. Advances in TIL-based therapies are driven by preclinical characterization and screening of TILs against a wide array of tumor types.
Prostate cancer is one of the most common forms of cancer that affects the prostate gland in the male urogenital tract. Most prostate cancers are slow growing and are detected in individuals older than age 50. Although environmental factors contribute to the development of prostate cancer, risk is significantly associated with incidence among first-degree relatives. In recent years, several inherited and spontaneously mutated genes have been linked to prostate cancer. Here we highlight these findings and how they provide insight into the development of targeted prostate cancer therapies.
Importance of the Dataset
Diffuse Large B-Cell Lymphoma (DLBCL) is a cancer of the B cells and is the most common form of non-Hodgkin’s Lymphoma (NHL) among adults. Champions’ DLBCL models encompass various subtypes of the disease, including ABC (Activated B cell), GCB (Germinal Center B cell), and Richter. These models are well-characterized and include patient clinical attributes, disease status, treatment history and in vivo drug responses to a range of therapies, including CHOP or a Rituximab-CHOP (R-CHOP) combination treatment. Champions DLBCL model cohort includes diverse molecular features such as double and triple hit mutations, as well as mutations in several key pathways such as proliferation, oncogenic signaling, and B cell differentiation. This unique dataset includes next generation sequencing (NGS), proteomics and phospho-proteomics from Champions’ DLBCL cohort.
Preclinical In Vivo Imaging is a technique that allows scientists to observe biological processes at the cellular level in real time. Preclinical In Vivo Imaging has been especially useful for imaging the tumor microenvironment (TME) and tracking the complex interactions between tumor cells and immune system cells that can result in tumor growth and development or tumor regression. Preclinical In Vivo Imaging is a noninvasive technique that relies on visualization of specific cells that emit light through bioluminescent reactions that can be detected within living animal models with highly sensitive cameras. Here we provide an overview of bioluminescence-based Preclinical In Vivo Imaging methods that are being used in preclinical oncology research.
Chronic lymphocytic leukemia (CLL) is one of the most commonly occurring hematologic malignances with no known cure and is defined by the clonal expansion and accumulation of CD5+ B cells in the blood and bone marrow. Standard treatments to manage disease include chemotherapy and rituximab (anti-CD20 monoclonal antibody). Newer therapies that are less prone to resistance or treatment failure are currently being examined, such as Bruton tyrosine kinase (BTK) inhibitors and anti-CD20 biosimilars,.
Champions Oncology is illuminating the cellular dynamics of cancer by providing a tool to accelerate biomarker discovery for all cancer researchers. Champions proprietary PDX (patient-derived xenograft) models have been shown to recapitulate patient response to clinical treatments1. The Lumin Bioinformatics platform incorporates NGS and proteomic data obtained from Champions unique and highly characterized PDX tumor bank as well as publicly available data sets (i.e. TCGA, CPTAC, GEO).
Ovarian cancer remains one of the leading causes of mortality for women with gynecological cancers and continues to be associated with stubbornly low 5-year survival rates. Depending on the stage or type of ovarian cancer, localized treatments including surgical resection or radiation may be sufficient. Treatment of metastatic ovarian cancer may include surgery and radiation combined with chemotherapy. Hormone therapy is also typically combined with chemotherapy for targeted reduction of estrogen and/or stimulation of progesterone for the targeted treatment of ovarian stromal tumors that produce high levels of estrogen. Nonetheless, many of these treatments have limited efficacy for treating metastatic ovarian cancer.
The development of new oncology treatments has focused on strategies that alter immune responses. Many of these novel therapies use antibodies that bind to receptors on different immune cell subsets and either activate or suppress their functions depending on the immune response being targeted. Antibody-drug conjugates are also becoming more widely used for improved targeting of drugs to specific cell subsets. Flow cytometry-based receptor occupancy (RO) assays are a valuable tool for quantifying cell surface expression of target molecules and are used to generate pharmacodynamic (PD) data, which can be used with pharmacokinetic (PK) data to guide dosing strategies. Consider these different types of receptor occupancy assays as you develop the most useful tools for screening therapeutic molecules.
Bioluminescence imaging (BLI) is a highly sensitive non-invasive molecular imaging technique that has been used across biological research areas for insights into how tissues and organs function in real-time under normal physiological conditions or different disease states. BLI was developed using transgenic mice that expressed the luciferase enzyme as a reporter in specific cells. These cells can be visualized in the presence of oxidated luciferin substrate, which generates bioluminescent light (photons) that can be detected using microscope-based or portable photon detectors. This method can detect biologically active tumor cells and can monitor changes in the growth or clearance these cells because bioluminescence is an ATP-dependent process in living animals, . More recently, functional BLI probes have been developed that use caged luciferin substrates that must be cleaved through a specific biological process for luminescence. These functional probes have been useful in monitoring metabolism and enzyme activity, and such read-outs can be used to understand basic tumor biology or identify mechanisms of action for anti-tumor drugs.