Category Archives: Clinical & Research Blog

Extrachromosomal MET Amplification Spurs Drug Resistance in ROS1+ NSCLC

Non-small-cell lung cancer (NSCLC) is a genetically heterogeneous disease. In approximately 2% of NSCLC cases, the primary oncogenic mutation is a chromosomal rearrangement involving ROS1 (ROS proto-oncogene 1), where one of many diverse gene partners fuses to the 3’ kinase domain of ROS1 and results in the constitutive activation of the ROS1 receptor tyrosine kinase. The ROS1-targeted tyrosine kinase inhibitor (TKI) entrectinib is an FDA-approved treatment for patients with these ROS1 fusions (ROS1+ NSCLC) and has dramatically improved patient outcomes.

Known Cancer Driver Mutations Found in Endometrial Polyps at Low Allelic Frequencies

Endometrial polyps (EMPs) are localized overgrowths of endometrial tissue composed of endometrial glands, stroma, and blood vessels. The reported prevalence of EMPs increases with age and ranges from 8-35%, depending on the population studied. EMPs are considered benign, with a risk of malignancy of around 3%.

Cerebrovascular β-Amyloid Deposits Linked to Altered Gene Expression Profile in Mice with Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia in older adults. Cerebral amyloid angiopathy (CAA), which is characterized by the deposition of β-amyloid (Aβ) peptides within cerebral blood vessels, co-occurs with AD to some extent in 85-95% of AD cases and is an independent contributor to AD dementia. Indeed, cerebrovascular dysfunction, possibly resulting from Aβ deposits, has been implicated in early AD pathogenesis, preceding neuronal damage.

Loss of TP53 Promotes NEK2 Amplification, Spurring Multiple Myeloma Aggressiveness

In the broadest sense, cancer development is spurred by genetic abnormalities that result in oncogene activation and tumor suppressor gene inactivation. In multiple myeloma (MM), a hematological malignancy that affects plasma cells, the amplification of chromosome 1q and the deletion of chromosome 17p have both been shown to be related to disease progression and poor patient outcomes. Chromosome 1q contains several oncogenes including NEK2 (never in mitosis gene A-related kinase 2), which has been shown to promote tumor cell proliferation, metastasis, and drug resistance in MM and other cancer types.

New Oncogenic Mechanism Proposed for Basal-like Breast Cancer

The aggressive basal-like breast cancer (BLBC) subtype, which strongly correlates with triple-negative (ER- PR- HER2-) breast cancers, comprises 15-20% of all breast cancer cases and has a poor prognosis, largely resulting from a lack of a molecularly targeted treatment regimen. Loss of control of signaling pathways frequently triggers tumorigenesis, and molecules involved in these signaling pathways are frequent molecular treatment targets. However, the mechanisms of tumorigenesis in BLBCs have yet to be fully elucidated.

Pembrolizumab Post-AlloHCT Most Beneficial for PD-L1 Amplified Lymphomas

Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat a variety of hematologic malignancies and represents the best chance for cure for many patients with these disorders. The effectiveness of alloHCT relies primarily on graft-versus-tumor (GVT) reactivity facilitated by donor T cells, which