ID8: A syngeneic mouse model for testing ovarian cancer immunotherapies

ID8-Luc is a novel syngeneic mouse model developed to treat orthotopic ovarian cancer. Ovarian cancer remains a significant unmet medical need with a relative 5-year survival rate of 17% in patients diagnosed with highly advanced stage IV ovarian cancer.

Tumor models for pancreatic cancer

More than 90% of all pancreatic cancers are classified as ductal adenocarcinomas and, within the western-world, pancreatic cancer is the fourth leading cause of cancer related deaths. Prognosis with pancreatic cancer is extremely poor, with a 5-year relative survival rate of 5% and median survival of 3.5 months for patients with Stage III non-resectable tumors.1 Unfortunately, the incidence of pancreatic cancer has been on the rise while the 5-year survival rate has not changed. Surgical resection is the only potentially curative therapy, but only 10% of patients are diagnosed early enough for this to be an option and most who are eligible for surgery ultimately relapse. As with many other types of cancer, pancreatic cancer grows silently for years without any symptoms. In most cases diagnosis is not made until the cancer has grown outside of the pancreas to other proximal tissues and/or has metastasized. These patients are left with very few meaningful options. Therefore, effective novel therapies are sorely needed in treatment of pancreatic cancer.

HT-29 as a preclinical model for colorectal cancer

For men and women combined, colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. The American Cancer Society estimates that over 49,000 individuals will die of CRC in 2016. Fortunately, the death rate from CRC has been declining in both men and women over the past several decades. Early screening efforts along with improved treatment options are at least two of several likely reasons for this drop. However, while there are now more than one million CRC survivors in the United States, we will see over 95,000 new cases being diagnosed in 2016.

HCC70: A model of triple negative breast cancer

Triple negative breast cancer (TNBC), accounting for 15-20% of all breast cancers, lacks estrogen receptors, progesterone receptors, and amplification or overexpression of Her-2. As such, these tumors are not responsive to hormonal or anti-Her2 therapies, and are usually treated with combinations of surgery, radiation, and chemotherapy. Although many triple negative tumors respond well to chemotherapy, patients generally have poorer prognosis, higher relapse rates with aggressive tumor growth, and high metastatic potential. More than 300 clinical trials are currently ongoing in TNBC (www.clinicaltrials.gov) evaluating various single agent and combination approaches with chemotherapy, targeted therapy, immunotherapy, and radiation therapy. Clinically, radiation therapy has been associated with decreased risk of locoregional recurrence and some instances of improved overall survival when compared to patients that did not receive radiation therapy.1, 2

EMT-6 syngeneic breast tumor model – a powerful tool for immuno-oncology studies

Breast cancer is the most common cancer among women in the United States and is the fourth leading cause of cancer death. In 2017, an estimated 252,710 new cases were diagnosed (15% of all new cancers) and 40,610 patient deaths occurred. Early detection initiatives together with improved treatment options have resulted in increases in the 5-year overall survival rate from 75% in 1975 to over 90% today.[1] Despite the favorable survival statistics, metastatic disease continues to be a treatment challenge and often results in death. For this reason, the continual development of new treatments for breast cancer is necessary.

E0771-syngeneic-breast-cancer-model

Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer lacking estrogen receptor, progesterone receptor, and HER2 amplifications; making it difficult to target therapeutically. Consequently, there’s a constant demand for better treatment options for TNBC. To help address the need for TNBC models, we highlighted the EMT6 model last month and herein we put forth the E0771 model, another TNBC syngeneic model for use in preclinical immuno-oncology. The E0771 cell line is a spontaneously developing medullary breast adenocarcinoma from C57BL/6 mice.[1] Parental E0771 is poorly metastatic when compared to 4T1[2] and has homozygous mutations in the Trp53 and KRAS genes.[3]

MB49 – a bladder cancer murine tumor model

Bladder cancer is one of the most frequent cancers of the urinary tract, accounting for about 80,000 new cases and 18,000 deaths in the United States in 2018, according to the National Cancer Society. Typically, patients with bladder cancer have limited surgical or treatment options. Traditional chemotherapeutics are ineffective, and surgery is often used to diagnose bladder cancer and to determine whether the cancer has spread into (invaded) the muscle layer of the bladder wall.  When bladder cancer is invasive, all or part of the bladder may need to be removed, leaving the patient with long term adverse effects. In an effort to meet the need for advances in bladder cancer treatment, in 2018 the FDA accelerated the approvals for two checkpoint inhibitors, Keytruda and Tecentriq.

MC38: An immunoresponsive murine tumor model

Colorectal cancer is the fourth most common cancer diagnosed in the United States. Colorectal cancer represents the third leading cause of cancer-related deaths in women and the second in men. In 2019, over 145,000 estimated new cases of colorectal cancer in the United States will be diagnosed and more than 51,000 patient deaths will occur. Prevention and early detection initiatives over the last several decades, together with improved treatment options, have resulted in reductions in colorectal cancer diagnoses and deaths. These measures have also increased the five-year overall survival rate to 64.9%, but survival drops precipitously for those patients whose cancer is not detected early.[1] For this reason, the development of new treatments for colorectal cancer is a continual need.

Phospho-protein detection in solid tumors using phospho-flow cytometry

In this article, we will be presenting phospho-protein detection in solid tumors using phospho-flow cytometry and reviewing the analysis of cabozantinib-induced inhibition of PI3K/AKT and JAK-STAT signaling in tumor vs. host immune cells.

D.P. Dash, PhD, PGCHET

Dr. D.P. Dash is a New York State Department of Health certified clinical Laboratory Director in Oncology (Molecular and Cellular Tumor Markers) and Genetics Testing (Molecular).  He earned his PhD in genomics at the Faculty of Medicine and Health Sciences, Queen’s University Belfast and a Postgraduate Certificate in Higher Education Teaching (PGCHET), also at Queen's University Belfast.  Dr.