Biological homeostasis is a state of steady internal, physical, and chemical conditions maintained by a living organism observed at the cellular level. Biological homeostasis can vary in order to alter the cellular physical and chemical conditions.
Melanoma is an aggressive form of skin cancer that commonly becomes metastatic, spreading to nearby tissue or other parts of the body, including distant skin or subcutaneous sites such as the lungs, liver, brain, or bone. Metastatic melanoma is very drug resistant and difficult to treat, and therefore, the prognosis for these patients is poor. There is a need for effective therapies for aggressive melanoma and other drug-resistant solid cancers.
The Zbtb7b gene encodes the zinc finger transcription factor ThPOK (also known as cKrox) that promotes CD4 lineage differentiation in immature T cells. CD4+ T cells, also known as “helper” T cells, are critical for long-term immunity against pathogens as well as for promoting CD8+ “effector” T cell and effective B cell responses. ThPOK is needed for the development and functional fitness of CD4+ T cells as well as multiple aspects of the immune response to infection. As such, ThPOK offers a potential target for immune regulation.
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.
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.
Topoisomerase 1 (TOP1) is an essential enzyme that plays a critical role in DNA transcription and replication. TOP1 inhibitors are a known class of anti-cancer agents that work to interrupt DNA replication in cancer cells, causing cell death. Since the discovery of the TOP1 inhibitor camptothecin (CPT) from plant extracts more than 60 years ago, two CPT analogs (irinotecan and topotecan) were approved by the FDA for cancer treatment. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme involved in DNA repair created when TOP1 is inhibited.
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.
Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes tumor infiltrating lymphocytes (TILs) or genetically engineered T cells to attack tumor cells through recognition of tumor-specific antigens. A major hurdle in the development of ACT is the identification and isolation of T cells that recognize antigens that are expressed by tumor cells but not by healthy tissues. Current methods to identify such T cells involve extracting autologous antigen presenting cells (APCs) from patients in an expensive, laborious, and time-consuming process.
BRAF is an oncogene that encodinges a serine-threonine kinase (B-Raf kinase) important in regulating cell growth and differentiation. Spontaneous mutations in the BRAF gene allow cells to continuously divide, leading to the development of cancer. A substitution of glutamic acid for valine at amino acid number 600 (designated V600E) accounts for 90% of BRAF mutations and is a driver of many cancers. The V600E mutation is present in ~3% of all cancer cases, representing a patient population of 540,000 patients per year.
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.