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.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common forms of cancer in the world. This heterogeneous disease is most often seen in men and is closely linked to tobacco usage, which can be enhanced by alcohol usage. Human papillomavirus (HPV) infection is an independent risk factor for HNSCC. Most HPV- HNSCCs occur in the larynx and oral cavity, and HPV+ HNSCCs typically arise in the oropharynx. Both HPV+ and HPV- HNSCCs are typically diagnosed at advanced disease stages and are often treated with an aggressive combination of surgery, radiotherapy (RT), and chemotherapy. More recently, cetuximab, an IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR) has been used in combination with radiotherapy and has shown some improvements in progression-free survival (PFS) and overall survival (OS).
Immunohistochemistry (IHC) is one of the oldest and widely used diagnostic techniques that continues to be a valuable tool for immuno-oncology research. IHC is a method for visualizing the tissue localization of specific antigens and has evolved since its development in the 1940s. This method has been an essential diagnostic tool for oncology because it enables pathologists to determine the histological grade of a tumor, which is a critical parameter for predicting the prognosis of tumors and determining the best treatment options. IHC is dependent on the skilled preparation and staining of thin tissue sections that are read by diagnostic pathologists or research scientists.