Acute myeloid leukemia (AML) is one of the most frequently occurring types of leukemia and can have widely varying treatment outcomes. Multiple mutations and cytogenetic abnormalities have been characterized in AML, and recent studies have been essential to defining specific mutations that confer resistance to standard chemotherapies or molecular inhibitors. A mutation in the tyrosine kinase domain of FMS-like tyrosine kinase 3 (FLT3) has been associated with resistance to FLT3 inhibitors, and molecular diagnostics are critical to identifying mutations that lead to treatment failure.
Plasmacytoid carcinoma of the urinary bladder – H&E Staining
Immunohistochemistry (IHC) is a technique that originates in the early twentieth century but continues to be a valuable method that forms the backbone of molecular pathology. IHC is used for histological examination of tissues and specifically detects the presence of a molecule, such as a tumor antigen. IHC uses antibody-based labeling in which the primary antibody detects the target of interest and the secondary antibody detects the primary antibody which is linked to a molecule for microscopic visualization. Many different secondary antibody labeling modalities exist, including fluorescence, enzyme-mediated reactions and colloidal gold, and different labels are suited to specific microscopy platforms.
Consider these five aspects of IHC as you implement this technique in preclinical cancer research:
Advances in preclinical oncology research are dependent on gaining insights into tumor biology and applying these insights to the development of novel diagnostics or therapeutics. Next-generation sequencing (NGS) technology has been instrumental in bridging basic immuno-oncology findings and preclinical applications. Here we provide an overview of NGS applications that are transforming preclinical oncology research.
Hematologic malignancies include a wide array of lymphomas and leukemias that affect different immune cell subsets. Acute myelogenous leukemia (AML) is one of the most commonly occurring leukemias in adults and children. AML is a highly heterogenous disease that can be caused by spontaneous gene mutations or chromosomal translocations, which results in the proliferation of dysfunctional myeloid cells. Cytogenetic and morphologic analyses have been the gold standard methods used in AML diagnosis, but flow cytometry-based protocols are becoming more widely used and validated as complementary diagnostic methods that can be coupled with these analyses to better guide treatment plans. Flow cytometry has also become an essential tool to understand AML progression and develop and evaluate novel therapeutics.
Consider these aspects of flow cytometry-based analysis of AML for exploratory or preclinical research.
Advances in molecular diagnostics and ex vivo drug sensitivity screening have greatly improved the use of targeted therapies for the treatment of chronic lymphocytic leukemia (CLL), such as B cell receptor signaling inhibitors, which include the Bruton tyrosine kinase (BTK) inhibitors like ibrutinib and acalabrutinib and the phosphoinositide 3-kinase (PI3K) inhibitors duvelisib and idelalisib, as well as the BCL2 inhibitor venetoclax. For most patients that are matched appropriately with these treatments, they show greatly improved progression-free survival and overall survival.
Bladder cancer is a relatively common form of cancer that is defined as either pre-invasive or invasive, and non-muscle invasive bladder cancer (NMIBC) is the most-commonly diagnosed subtype. NMIBC is typically treated by surgical resection and/or intravesical delivery of chemo- or immunotherapy-based adjuvant treatment, and long-term efficacy is monitored by urine testing or cystoscopy. Muscle-invasive bladder cancer (MIBC) is relatively resistant to current treatment options and occurs more frequently in men. MIBC also has high rates of morbidity and mortality, and novel therapies or combination therapies area being developed to better treat this form of bladder cancer.
Here we highlight recent findings about invasive bladder cancer biology and how these observations are informing the development of new therapies.
Glioblastoma multiforme (GBM) is an aggressive form of primary malignancy of the central nervous system (CNS) that causes brain tumors. GBM has been associated with poor prognoses and high mortality rates and a 5-year relative survival rate ranging from 6-22% percent depending on age of onset. Currently, standard-of-care treatments include cytoreductive surgery followed by chemoradiotherapy, but these are not considered curative treatments, and efficacy varies widely between patients. Temozolomide is a DNA alkylating agent prodrug commonly used for adjuvant chemotherapy in GBM, but treatment resistance is a common occurrence, and this drug is also associated with clinically significantly toxicity.
Answers provided by Alexis Santana, PhD – Manager, Business Development at Champions Oncology
Adoptive cell therapies (ACTs) are being broadly tested and implemented in the treatment of a wide range of cancers, but the success of these therapies has been limited by the challenges of expanding cells of interest ex vivo. Most studies collect peripheral blood cells from a patient and expand, enrich or modify tumor-specific cells in a laboratory environment to create a blood product with tumor-targeting cells that can be reinfused into the patient. If the blood product is re-infused into the same patient, it is considered an autologous transplant, but if the cells originate from a different donor, it is considered an allogeneic transplant.
The current landscape for immunotherapy treatment of blood cancers has been advanced by breakthroughs in molecular diagnostics and personalized medicine. Now patients not only know the type of hematologic malignancy they have, but they may also be aware of unique mutations or variations associated with their cancer that can instruct treatment choices.