Targeting CRAF kinase in anti-cancer therapy: progress and opportunities

Abstract The RAS/mitogen-activated protein kinase (MAPK) signaling cascade is commonly dysregulated in human malignancies by processes driven by RAS or RAF oncogenes. Among the members of the RAF kinase family, CRAF plays an important role in the RAS-MAPK signaling pathway, as well as in the progression of cancer. Recent research has provided evidence implicating the role of CRAF in the physiological regulation and the resistance to BRAF inhibitors through MAPK-dependent and MAPK-independent mechanisms. Nevertheless, the effectiveness of solely targeting CRAF kinase activity remains controversial. Moreover, the kinase-independent function of CRAF may be essential for lung cancers with KRAS mutations. It is imperative to develop strategies to enhance efficacy and minimize toxicity in tumors driven by RAS or RAF oncogenes. The review investigates CRAF alterations observed in cancers and unravels the distinct roles of CRAF in cancers propelled by diverse oncogenes. This review also seeks to summarize CRAF-interacting proteins and delineate CRAF's regulation across various cancer hallmarks. Additionally, we discuss recent advances in pan-RAF inhibitors and their combination with other therapeutic approaches to improve treatment outcomes and minimize adverse effects in patients with RAF/RAS-mutant tumors. By providing a comprehensive understanding of the multifaceted role of CRAF in cancers and highlighting the latest developments in RAF inhibitor therapies, we endeavor to identify synergistic targets and elucidate resistance pathways, setting the stage for more robust and safer combination strategies for cancer treatment

Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

Abstract The CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins (SRSF1–12), catalyzing spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. The dysregulation of these processes is linked with various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Thus, CLKs have been considered as potential therapeutic targets, and significant efforts have been exerted to discover potent CLKs inhibitors. In particular, clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients, and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage. In this review, we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics. Our discussion highlights the most recent CLKs research, paving the way for the clinical treatment of various human diseases

Kcnq1-5 (Kv7.1-5) potassium channel expression in the adult zebrafish

In this article, the authors use the zebrafish genome and potassium channels to study cardiac anomalies, epilepsy, convulsions, hearing loss, and tinnitus in humans

Creating an Artificial Pancreas (Semester Unknown) IPRO 308: Creating an Artificial Pancreas IPRO 308 Project Plan Sp08

Insulin is a hormone released by pancreatic islet cells that interacts with cells to increase their permeability to glucose. Diabetes is an illness that is becoming more prevalent around the world and is linked with either abnormal insulin production, or utilization or both in the body. Diabetes may be classified into two groups: Type 1 and Type 2 In an individual with Type 1 diabetes, the pancreatic ß cells that normally produce insulin are nonexistent as they have been destroyed due to autoimmune response. In an individual with Type 2 diabetes there is tissue-wide resistance to insulin and usually some impairment of ß cells as well. Therefore, although insulin production may be present its functionality is impaired. Type 1 diabetes is typically treated with frequent extraneous insulin injections, depending on the prevailing blood glucose levels of the individual; however, in order to determine the glucose levels individuals subject themselves to periodic finger pricks throughout the day which is often uncomfortable and stressful. Mechanical devices for insulin delivery, also known as “artificial pancreases”, are currently available in the marketplace. However, these devices are not only highly invasive and painful, but also must be sanitized frequently to prevent infections. As a result, they are inconvenient and many diabetic patients choose not to use them. The goal of IPRO 308 is to develop an automated, non-invasive artificial pancreas that will be capable of determining blood glucose levels and administering an appropriate amount of insulin into the blood stream while causing minimal discomfort to the individual.Deliverable

Creating an Artificial Pancreas (Semester Unknown) IPRO 308

Insulin is a hormone released by pancreatic islet cells that interacts with cells to increase their permeability to glucose. Diabetes is an illness that is becoming more prevalent around the world and is linked with either abnormal insulin production, or utilization or both in the body. Diabetes may be classified into two groups: Type 1 and Type 2 In an individual with Type 1 diabetes, the pancreatic ß cells that normally produce insulin are nonexistent as they have been destroyed due to autoimmune response. In an individual with Type 2 diabetes there is tissue-wide resistance to insulin and usually some impairment of ß cells as well. Therefore, although insulin production may be present its functionality is impaired. Type 1 diabetes is typically treated with frequent extraneous insulin injections, depending on the prevailing blood glucose levels of the individual; however, in order to determine the glucose levels individuals subject themselves to periodic finger pricks throughout the day which is often uncomfortable and stressful. Mechanical devices for insulin delivery, also known as “artificial pancreases”, are currently available in the marketplace. However, these devices are not only highly invasive and painful, but also must be sanitized frequently to prevent infections. As a result, they are inconvenient and many diabetic patients choose not to use them. The goal of IPRO 308 is to develop an automated, non-invasive artificial pancreas that will be capable of determining blood glucose levels and administering an appropriate amount of insulin into the blood stream while causing minimal discomfort to the individual.Deliverable

Creating an Artificial Pancreas (Semester Unknown) IPRO 308: Creating an Artificial Pancreas IPRO 308 Final Report Sp08_redacted

Insulin is a hormone released by pancreatic islet cells that interacts with cells to increase their permeability to glucose. Diabetes is an illness that is becoming more prevalent around the world and is linked with either abnormal insulin production, or utilization or both in the body. Diabetes may be classified into two groups: Type 1 and Type 2 In an individual with Type 1 diabetes, the pancreatic ß cells that normally produce insulin are nonexistent as they have been destroyed due to autoimmune response. In an individual with Type 2 diabetes there is tissue-wide resistance to insulin and usually some impairment of ß cells as well. Therefore, although insulin production may be present its functionality is impaired. Type 1 diabetes is typically treated with frequent extraneous insulin injections, depending on the prevailing blood glucose levels of the individual; however, in order to determine the glucose levels individuals subject themselves to periodic finger pricks throughout the day which is often uncomfortable and stressful. Mechanical devices for insulin delivery, also known as “artificial pancreases”, are currently available in the marketplace. However, these devices are not only highly invasive and painful, but also must be sanitized frequently to prevent infections. As a result, they are inconvenient and many diabetic patients choose not to use them. The goal of IPRO 308 is to develop an automated, non-invasive artificial pancreas that will be capable of determining blood glucose levels and administering an appropriate amount of insulin into the blood stream while causing minimal discomfort to the individual.Deliverable

Creating an Artificial Pancreas (Semester Unknown) IPRO 308: Creating an Artificial Pancreas IPRO 308 Brochure Sp08

Insulin is a hormone released by pancreatic islet cells that interacts with cells to increase their permeability to glucose. Diabetes is an illness that is becoming more prevalent around the world and is linked with either abnormal insulin production, or utilization or both in the body. Diabetes may be classified into two groups: Type 1 and Type 2 In an individual with Type 1 diabetes, the pancreatic ß cells that normally produce insulin are nonexistent as they have been destroyed due to autoimmune response. In an individual with Type 2 diabetes there is tissue-wide resistance to insulin and usually some impairment of ß cells as well. Therefore, although insulin production may be present its functionality is impaired. Type 1 diabetes is typically treated with frequent extraneous insulin injections, depending on the prevailing blood glucose levels of the individual; however, in order to determine the glucose levels individuals subject themselves to periodic finger pricks throughout the day which is often uncomfortable and stressful. Mechanical devices for insulin delivery, also known as “artificial pancreases”, are currently available in the marketplace. However, these devices are not only highly invasive and painful, but also must be sanitized frequently to prevent infections. As a result, they are inconvenient and many diabetic patients choose not to use them. The goal of IPRO 308 is to develop an automated, non-invasive artificial pancreas that will be capable of determining blood glucose levels and administering an appropriate amount of insulin into the blood stream while causing minimal discomfort to the individual.Deliverable

Creating an Artificial Pancreas (Semester Unknown) IPRO 308: Creating an Artificial Pancreas IPRO 308 Ethics Sp08

Insulin is a hormone released by pancreatic islet cells that interacts with cells to increase their permeability to glucose. Diabetes is an illness that is becoming more prevalent around the world and is linked with either abnormal insulin production, or utilization or both in the body. Diabetes may be classified into two groups: Type 1 and Type 2 In an individual with Type 1 diabetes, the pancreatic ß cells that normally produce insulin are nonexistent as they have been destroyed due to autoimmune response. In an individual with Type 2 diabetes there is tissue-wide resistance to insulin and usually some impairment of ß cells as well. Therefore, although insulin production may be present its functionality is impaired. Type 1 diabetes is typically treated with frequent extraneous insulin injections, depending on the prevailing blood glucose levels of the individual; however, in order to determine the glucose levels individuals subject themselves to periodic finger pricks throughout the day which is often uncomfortable and stressful. Mechanical devices for insulin delivery, also known as “artificial pancreases”, are currently available in the marketplace. However, these devices are not only highly invasive and painful, but also must be sanitized frequently to prevent infections. As a result, they are inconvenient and many diabetic patients choose not to use them. The goal of IPRO 308 is to develop an automated, non-invasive artificial pancreas that will be capable of determining blood glucose levels and administering an appropriate amount of insulin into the blood stream while causing minimal discomfort to the individual.Deliverable

Creating an Artificial Pancreas (Semester Unknown) IPRO 308: Creating an Artificial Pancreas IPRO 308 Poster Sp08

Insulin is a hormone released by pancreatic islet cells that interacts with cells to increase their permeability to glucose. Diabetes is an illness that is becoming more prevalent around the world and is linked with either abnormal insulin production, or utilization or both in the body. Diabetes may be classified into two groups: Type 1 and Type 2 In an individual with Type 1 diabetes, the pancreatic ß cells that normally produce insulin are nonexistent as they have been destroyed due to autoimmune response. In an individual with Type 2 diabetes there is tissue-wide resistance to insulin and usually some impairment of ß cells as well. Therefore, although insulin production may be present its functionality is impaired. Type 1 diabetes is typically treated with frequent extraneous insulin injections, depending on the prevailing blood glucose levels of the individual; however, in order to determine the glucose levels individuals subject themselves to periodic finger pricks throughout the day which is often uncomfortable and stressful. Mechanical devices for insulin delivery, also known as “artificial pancreases”, are currently available in the marketplace. However, these devices are not only highly invasive and painful, but also must be sanitized frequently to prevent infections. As a result, they are inconvenient and many diabetic patients choose not to use them. The goal of IPRO 308 is to develop an automated, non-invasive artificial pancreas that will be capable of determining blood glucose levels and administering an appropriate amount of insulin into the blood stream while causing minimal discomfort to the individual.Deliverable