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.
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.
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.
Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes autologous, antitumor T cells to attack tumors through recognition of tumor-specific mutations, or neoantigens. A major hurdle in the development of ACT is the exhausted phenotype exhibited by many neoantigen-specific T cells, which limits their efficacy and prevents a sustained immune response.
Vaccines have become one of the most important tools in the fight against cancers and infectious diseases. However, some vaccines have shown limitations due to their high cost and low immune responses. To overcome these limitations, bacteriophages were proposed for the development of more cost-effective, immunogenic vaccines. Phages have shown a strong ability to activate induced and adaptive immune systems. The genome of these viral particles can be engineered, and their surface proteins can be exploited for antigen display.
Human papillomavirus (HPV) is a group of human viruses known to cause various malignancies. Of the group, HPV-16 is the most prevalent strain – an estimated 90% of adults have been exposed. HPV-16 is also the strain most commonly associated with malignancy, causing the vast majority of cervical, anal, vaginal, vulvar, and penile cancers. Currently, HPV-positive malignancies non-responsive to surgery or radiation are incurable and poorly palliated by existing systemic therapies. Thus, an alternative therapeutic approach for HPV-positive malignancies is needed.
