Proviral Integration for the Moloney murine leukemia virus (PIM) kinases are overexpressed in many solid cancers – including prostate, breast, colon, endometrial, gastric and pancreatic. High of PIM1 expression is predictive of poor survival in multiple cancer types. While several selective pan-PIM inhibitors were developed and tested in clinical trials, all ultimately increased PIM1-3 protein levels and developed intrinsic resistance.
Neuroblastomas are the most common extracranial solid tumors in pediatric patients, with 700-800 new cases annually in the United States. Metastatic neuroblastomas have a five-year survival rate of 50% and account for 15% of all pediatric cancer deaths. As such, more effective treatments against high-risk neuroblastomas are urgently needed.
The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. Almost all the neutralizing antibodies targeting SARS-CoV-2 that are in development recognize the receptor binding domain (RBD) on the spike (S) protein. Blocking the interaction of RBD and the ACE2 receptor on human cells is the first of the two critical steps for neutralization of the virus.
Cyclin-dependent kinase inhibitor 2A gene, also known as CDKN2A, is a tumor suppressor gene and is commonly inactivated through somatic mutations in many human cancers. For example, inactivation of CDKN2A is highly prevalent in melanoma, gastrointestinal and pancreatic cancers. Through germline mutations, CDKN2A is associated with predisposition for a variety of cancers, including melanoma and pancreatic cancers. Despite the high frequency of CDKN2A mutations in cancer, there have been no successful therapies targeting these mutations to date.
Human immunodeficiency virus (HIV) remains a major global health challenge despite the advancement made in development of effective antiretrovirals (ARVs). ARVs are effective at limiting replication and spread of the virus, and progression to acquired immuno-deficiency syndrome (AIDS). However, ARVs often lead to emergence of drug-resistant virus strains insensitive to treatment and with toxic effects following long-term usage.
DNA or RNA-based diagnostic tests for infectious diseases are critical in modern medicine. The current gold standard for COVID-19 detection is testing SARS-CoV-2 viral RNA by quantitative reverse transcription Polymerase Chain Reaction (RT-qPCR). This method involves patient sample collection with a nasopharyngeal swab, storage of the swab in a universal transport medium during transport to testing site, RNA extraction, and analysis of the extracted RNA sample.
There are no effective treatments for Alzheimer’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk.
Millions of patients in the United States are afflicted by a host of bone diseases caused by osteoclast (specialized calls arising from the macrophage/monocyte lineage) dysfunction. Diseases include Paget’s disease, osteoporosis, fibrous dysplasia and osteolytic bone metastasis. The current standard of care for these diseases uses broad-spectrum therapies that either coat the skeletal system or inhibit osteoclast development in an effort to modulate osteoclastogenesis.
Traumatic brain injury (TBI) represents a major medical, social and economic concern worldwide due to significant mortality – especially among younger populations – and long-term disabilities. Various pathological brain lesions (e.g., intracerebral bleedings, necrotic-ischemic lesions, tissue avulsion) are produced by impacting mechanical forces. Among these, diffuse axonal injury (DAI) is one of the most significant brain lesions typically associated with trauma. However, DAI is not necessarily linked with TBI exposure. Therefore, the term “traumatic axonal injury (TAI)” is commonly used.
