Anticancer ( rituximab ), monoclonal antibody
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Rituximab is a monoclonal antibody approved for use in drug-resistant follicular lymphoma and diffuse large B-cell lymphoma in combination with other drugs. It targets the CD20 antigen on pre-B and mature B-lymphocytes, mediating B-cell lysis through complement dependent cytotoxicity and antibody dependent cell-mediated cytotoxicity. Rituximab belongs to the IgG1 subclass, with a murine variable region and human constant region. Side effects require caution during pregnancy.
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Rituximab.pptx
Rituximab is a chimeric monoclonal antibody that binds to the CD20 antigen found on B cells. It works through antibody-dependent cell-mediated and complement-dependent cytotoxicity to induce cell death. Rituximab is approved for treatment of B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, vasculitis, and pemphigus vulgaris. Common adverse effects include infusion reactions and increased risk of infections. Rituximab is administered by intravenous infusion and has contraindications for severe infections and hypersensitivity.
TYROSINE KINASE INHIBITORS
This document discusses tyrosine kinase inhibitors, which are drugs that target tyrosine kinases. It begins by introducing tyrosine kinases and their role in cell signaling pathways. It then describes several important tyrosine kinase inhibitors, including BCR-ABL inhibitors like imatinib, dasatinib, and nilotinib; EGFR inhibitors like gefitinib and erlotinib; and VEGF inhibitors like sunitinib and sorafenib. For each drug, it provides information on mechanisms of action, pharmacokinetics, dosing, toxicity profiles, and FDA-approved indications. The document concludes by discussing mechanisms of resistance to BCR-ABL kinase inhibitors.
Oral tyrosine kinase inhibitors
Imatinib is the first FDA approved targeted protein kinase inhibitor for chronic myelogenous leukemia and gastrointestinal stromal tumors. It binds to and inactivates the BCR-ABL tyrosine kinase. Dasatinib and nilotinib are also BCR-ABL tyrosine kinase inhibitors approved for CML. Gefitinib, erlotinib and lapatinib inhibit the epidermal growth factor receptor tyrosine kinase and are approved for various cancers. Sunitinib, sorafenib, pazopanib, and vatalanib inhibit vascular endothelial growth factor receptors and are approved for renal cell carcinoma and other cancers. These oral tyrosine kinase inhibitors are important targeted cancer therapies.
Tyrosine kinase inhibitors
TKI introduction and some of its drugs and side effects
many thanks to Vijay Yerroju
most of the info is taken from his presentation on TKI
Cancer vaccines Presentation
Cancer vaccines aim to stimulate the immune system to recognize and destroy cancer cells. There are two major types: specific vaccines target individual cancer types, while universal vaccines target common cancer antigens. Cancer vaccines work by exposing the immune system to tumor antigens, stimulating immune cells to develop a memory and mount an attack against cancer cells displaying those antigens. Currently, many types of cancer vaccines are under clinical trials, including antigen vaccines, dendritic cell vaccines, and DNA vaccines targeting cancers like melanoma, prostate cancer, and lung cancer. The goal is to develop safe and effective personalized or broad-spectrum vaccines to help treat and prevent cancer.
ACUTE MYELOID LEUKEMIA
ACUTE MYELOID LEUKEMIA
Jeffrey E. Lancet, MD, Moffitt Cancer Center
Sara Tinsley, Ph.D., ARNP, AOCN, Moffitt Cancer Center
Targeted cancer therapies
This document discusses various targeted cancer therapies including monoclonal antibodies, small molecule inhibitors, and other targeted agents. It describes key targets of these therapies such as protein kinases, growth factor receptors, angiogenesis pathways, and nuclear factors. Specific drugs are discussed that target ABL, EGFR, VEGFR, mTOR, MAPK pathways, and the proteasome. Resistance mechanisms and combination approaches are also mentioned.
Monoclonal antibodies in cancer therapy
Monoclonal antibodies can be used in cancer therapy in several ways:
1) They can bind to cancer cell antigens and recruit the immune system to attack the cancer cells or block growth signaling pathways.
2) They can be conjugated to toxins, enzymes, or radioisotopes to directly kill cancer cells after binding.
3) By inhibiting immune checkpoint proteins like CTLA-4 and PD-1, they can enhance the immune system's antitumor response.
4) Examples of monoclonal antibodies used in cancer include rituximab for blood cancers, trastuzumab for HER2-positive breast cancer, and immune checkpoint inhibitors like nivolumab and pembrolizumab.
Recommended
Rituximab.pptx
Rituximab is a chimeric monoclonal antibody that binds to the CD20 antigen found on B cells. It works through antibody-dependent cell-mediated and complement-dependent cytotoxicity to induce cell death. Rituximab is approved for treatment of B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, vasculitis, and pemphigus vulgaris. Common adverse effects include infusion reactions and increased risk of infections. Rituximab is administered by intravenous infusion and has contraindications for severe infections and hypersensitivity.
TYROSINE KINASE INHIBITORS
This document discusses tyrosine kinase inhibitors, which are drugs that target tyrosine kinases. It begins by introducing tyrosine kinases and their role in cell signaling pathways. It then describes several important tyrosine kinase inhibitors, including BCR-ABL inhibitors like imatinib, dasatinib, and nilotinib; EGFR inhibitors like gefitinib and erlotinib; and VEGF inhibitors like sunitinib and sorafenib. For each drug, it provides information on mechanisms of action, pharmacokinetics, dosing, toxicity profiles, and FDA-approved indications. The document concludes by discussing mechanisms of resistance to BCR-ABL kinase inhibitors.
Oral tyrosine kinase inhibitors
Imatinib is the first FDA approved targeted protein kinase inhibitor for chronic myelogenous leukemia and gastrointestinal stromal tumors. It binds to and inactivates the BCR-ABL tyrosine kinase. Dasatinib and nilotinib are also BCR-ABL tyrosine kinase inhibitors approved for CML. Gefitinib, erlotinib and lapatinib inhibit the epidermal growth factor receptor tyrosine kinase and are approved for various cancers. Sunitinib, sorafenib, pazopanib, and vatalanib inhibit vascular endothelial growth factor receptors and are approved for renal cell carcinoma and other cancers. These oral tyrosine kinase inhibitors are important targeted cancer therapies.
Tyrosine kinase inhibitors
TKI introduction and some of its drugs and side effects
many thanks to Vijay Yerroju
most of the info is taken from his presentation on TKI
Cancer vaccines Presentation
Cancer vaccines aim to stimulate the immune system to recognize and destroy cancer cells. There are two major types: specific vaccines target individual cancer types, while universal vaccines target common cancer antigens. Cancer vaccines work by exposing the immune system to tumor antigens, stimulating immune cells to develop a memory and mount an attack against cancer cells displaying those antigens. Currently, many types of cancer vaccines are under clinical trials, including antigen vaccines, dendritic cell vaccines, and DNA vaccines targeting cancers like melanoma, prostate cancer, and lung cancer. The goal is to develop safe and effective personalized or broad-spectrum vaccines to help treat and prevent cancer.
ACUTE MYELOID LEUKEMIA
ACUTE MYELOID LEUKEMIA
Jeffrey E. Lancet, MD, Moffitt Cancer Center
Sara Tinsley, Ph.D., ARNP, AOCN, Moffitt Cancer Center
Targeted cancer therapies
This document discusses various targeted cancer therapies including monoclonal antibodies, small molecule inhibitors, and other targeted agents. It describes key targets of these therapies such as protein kinases, growth factor receptors, angiogenesis pathways, and nuclear factors. Specific drugs are discussed that target ABL, EGFR, VEGFR, mTOR, MAPK pathways, and the proteasome. Resistance mechanisms and combination approaches are also mentioned.
Monoclonal antibodies in cancer therapy
Monoclonal antibodies can be used in cancer therapy in several ways:
1) They can bind to cancer cell antigens and recruit the immune system to attack the cancer cells or block growth signaling pathways.
2) They can be conjugated to toxins, enzymes, or radioisotopes to directly kill cancer cells after binding.
3) By inhibiting immune checkpoint proteins like CTLA-4 and PD-1, they can enhance the immune system's antitumor response.
4) Examples of monoclonal antibodies used in cancer include rituximab for blood cancers, trastuzumab for HER2-positive breast cancer, and immune checkpoint inhibitors like nivolumab and pembrolizumab.
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This document discusses targeted cancer therapies, which work by interfering with specific molecular targets involved in cancer growth and progression, unlike traditional chemotherapy which acts on all rapidly dividing cells. It provides examples of molecular targets for small molecule drugs and monoclonal antibodies, including growth factor receptors and fusion proteins. The document also discusses methods of target identification, categories of targeted therapies, examples of FDA-approved targeted drugs, limitations and side effects of targeted therapies, and concludes by emphasizing the importance and promise of targeted therapies while noting challenges that remain.
Multiple myeloma
Multiple myeloma is a cancer of plasma cells that results in overproduction of abnormal antibodies in the bone marrow. It commonly causes bone pain, fractures, anemia, and kidney problems. Risk factors include age over 60 and exposure to chemicals like pesticides, radiation, or certain industrial chemicals. Treatment may include chemotherapy, steroids, stem cell transplantation, radiation, surgery, and newer drugs like thalidomide, lenalidomide, and bortezomib to improve outcomes. Despite recent advances, multiple myeloma remains incurable and patients often relapse, highlighting the need for additional therapeutic options.
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Vancomycin was first discovered in 1950 and approved by the FDA in 1958. It became a standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections in the 1980s. Vancomycin works by inhibiting peptidoglycan biosynthesis in the bacterial cell wall. It has activity against gram-positive bacteria and is used to treat various hospital-acquired infections caused by MRSA such as pneumonia, bloodstream infections, and surgical site infections. Key considerations for vancomycin treatment include monitoring for potential adverse effects like red man syndrome, nephrotoxicity, and ototoxicity. Therapeutic drug monitoring is important to maintain concentrations above the minimum inhibitory concentration for optimal bacterial killing
Targeted therapy anticancer drugs
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
Janus kinase inhibitors
This document discusses Janus kinase (JAK) inhibitors for treating myeloproliferative neoplasms and other hematologic cancers. It describes the JAK family proteins and the recurrent JAK2V617F mutation found in many of these cancers. The JAK2V617F mutation results in constitutive JAK/STAT signaling that promotes proliferation. Several JAK inhibitors in clinical trials are described, including ruxolitinib, which selectively inhibits JAK1/JAK2 and showed promising results for primary myelofibrosis in Phase III trials. Other JAK2-selective inhibitors like TG101348, lestaurtinib, XL019 and SB1518 are also summarized.
Anthracyclines
Anthracyclines are a class of chemotherapy drugs that act as topoisomerase II inhibitors. Doxorubicin and daunorubicin were the first anthracyclines developed in the 1960s from bacteria. They intercalate DNA, inhibit topoisomerase and DNA synthesis, and generate free radicals causing DNA damage. Chronic cardiotoxicity is the main toxicity, with risk increasing with cumulative dose. Liposomal doxorubicin and mitoxantrone have less cardiotoxicity. Anthracyclines are used to treat many cancers but dose adjustments are needed for hepatic or renal dysfunction.
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This document discusses multi-drug resistant tuberculosis (MDR-TB). It provides global and country-specific data on TB incidence and burden. MDR-TB is defined as disease resistant to at least two anti-TB drugs. Countries with high MDR-TB burdens are identified. The Indian scenario of TB is described, noting prevalence of MDR-TB in new and previously treated cases. A case study from Andhra Pradesh reports findings from 75 MDR-TB patients. Clinical factors promoting drug resistance and mechanisms of resistance are outlined. Treatment of MDR-TB and new chemotherapeutic agents are discussed. Global plans to combat TB, including targets and strategies, are summarized.
Leprosy
1) Lepra reactions are immunologically inflammatory states that can occur in leprosy patients. There are two main types - Type 1 reactions (downgrading and reversal reactions) and Type 2 reactions (Erythema Nodosum Leprosum or ENL).
2) Type 1 reactions involve the skin and nerves and cause swelling and tenderness. They occur after treatment begins. Type 2 or ENL reactions cause painful swollen skin lesions and other symptoms like fever. They typically occur after treatment in lepromatous patients.
3) Histologically, Type 1 reactions show edema while Type 2 reactions show deep inflammation, necrosis and few bacilli. Both can cause significant morbidity if not properly treated.
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This document discusses multi-drug resistant tuberculosis (MDR TB). It begins with an introduction to TB and definitions of key terms like MDR and XDR TB. It then describes first and second line anti-TB drugs, mechanisms of drug resistance, and factors contributing to acquired resistance. The document outlines methods for diagnosing drug resistance including genetic detection and drug sensitivity testing. It concludes with a brief overview of treatment approaches for MDR TB.
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i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Monoclonal antibodies
Monoclonal antibodies are man-made versions of antibodies that are identical because they were produced by one type of immune cell. They can be designed to attack very specific parts of cancer cells. The main types used in cancer immunotherapy are naked monoclonal antibodies, conjugated monoclonal antibodies (attached to chemotherapy drugs or radioactive particles), and bispecific monoclonal antibodies (attached to two different antigens). Immunotherapy treatments that target immune checkpoint proteins like PD-1, PD-L1, and CTLA-4 have also shown promise in treating cancers. Non-specific immunotherapies like cytokines can generally stimulate the immune system to potentially help it better attack cancer cells.
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Immune checkpoint inhibitors can cause immune-related adverse events by removing inhibitory checkpoints and excessively activating the immune system. Common adverse effects include dermatitis in over 50% of patients, enterocolitis in under 20%, hepatitis in under 10%, and endocrinopathies. Symptoms usually onset several months after treatment. Management involves stopping the immune checkpoint inhibitor and administering corticosteroids in most cases. Life-threatening hyperimmunity is possible so consulting the oncologist and other specialists is important.
Chronic Lymphocytic Leukemia
The document discusses chronic lymphocytic leukemia (CLL), including its definition, epidemiology, etiology, pathogenesis, clinical symptoms, diagnosis, staging, prognosis, and treatment. Some key points:
- CLL is characterized by the proliferation and accumulation of small, mature lymphocytes in the blood, bone marrow, and lymphoid tissues. It most commonly affects elderly adults.
- Diagnosis is based on blood cell counts and immunophenotyping of lymphocytes. Prognosis depends on factors like clinical stage, genomic abnormalities, and biomarker expression levels.
- Treatment involves chemotherapy, chemoimmunotherapy, targeted therapies, and supportive care. The appropriate treatment approach depends on a patient's risk
Temozolomide
Temozolomide (TMZ) is an orally administered alkylating agent that is used as the first-line treatment for glioblastoma multiforme (GBM) due to its proven efficacy and good safety profile. TMZ works by methylating DNA at specific positions, and its cytotoxic effects require an intact DNA mismatch repair system and low levels of the DNA repair enzyme O6-methylguanine DNA methyltransferase. The standard dosing regimen for TMZ involves concurrent low-dose administration with radiation therapy followed by cycles of higher-dose adjuvant TMZ. Common side effects include nausea, vomiting, fatigue, and hematological toxicities.
Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by increased numbers of immature lymphocytes in the bone marrow. It is the most common cancer in children. Treatment involves chemotherapy given systemically and intrathecally in phases including induction, consolidation and maintenance to achieve and maintain remission. Prognosis depends on risk factors like age, white blood cell count, genetics. Late effects of intensive chemotherapy include secondary cancers, organ dysfunction. Relapse indicates poor prognosis requiring aggressive salvage therapies like stem cell transplant.
Methotrexate
Methotrexate is an antifolate drug that inhibits dihydrofolate reductase (DHFR), blocking the production of nucleotides needed for DNA synthesis. It is used to treat cancers like acute lymphoblastic leukemia as well as autoimmune diseases like rheumatoid arthritis. Methotrexate is transported into cells and polyglutamated, increasing its intracellular activity and half-life. It causes cell death by inhibiting DNA synthesis and inducing strand breaks. Resistance can develop through reduced polyglutamation, increased DHFR levels, or drug efflux pumps. The cytotoxic effects of methotrexate are S-phase specific and depend on drug concentration and duration of exposure.
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This document provides an overview of immunomodulators. It begins with definitions of immunity and antigens. It describes the types of immunity and components of the immune system. It then discusses mechanisms of immunomodulation and how drugs can suppress or stimulate the immune response. The document focuses on clinically used immunomodulators, dividing them into immunosuppressants and immunostimulants. Several commonly used immunosuppressants are described in detail, including their mechanisms of action, uses, and toxicities.
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Multiple myeloma
Multiple myeloma is a cancer of plasma cells that results in overproduction of abnormal antibodies in the bone marrow. It commonly causes bone pain, fractures, anemia, and kidney problems. Risk factors include age over 60 and exposure to chemicals like pesticides, radiation, or certain industrial chemicals. Treatment may include chemotherapy, steroids, stem cell transplantation, radiation, surgery, and newer drugs like thalidomide, lenalidomide, and bortezomib to improve outcomes. Despite recent advances, multiple myeloma remains incurable and patients often relapse, highlighting the need for additional therapeutic options.
Vancomycin
Vancomycin was first discovered in 1950 and approved by the FDA in 1958. It became a standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections in the 1980s. Vancomycin works by inhibiting peptidoglycan biosynthesis in the bacterial cell wall. It has activity against gram-positive bacteria and is used to treat various hospital-acquired infections caused by MRSA such as pneumonia, bloodstream infections, and surgical site infections. Key considerations for vancomycin treatment include monitoring for potential adverse effects like red man syndrome, nephrotoxicity, and ototoxicity. Therapeutic drug monitoring is important to maintain concentrations above the minimum inhibitory concentration for optimal bacterial killing
Targeted therapy anticancer drugs
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
Janus kinase inhibitors
This document discusses Janus kinase (JAK) inhibitors for treating myeloproliferative neoplasms and other hematologic cancers. It describes the JAK family proteins and the recurrent JAK2V617F mutation found in many of these cancers. The JAK2V617F mutation results in constitutive JAK/STAT signaling that promotes proliferation. Several JAK inhibitors in clinical trials are described, including ruxolitinib, which selectively inhibits JAK1/JAK2 and showed promising results for primary myelofibrosis in Phase III trials. Other JAK2-selective inhibitors like TG101348, lestaurtinib, XL019 and SB1518 are also summarized.
Anthracyclines
Anthracyclines are a class of chemotherapy drugs that act as topoisomerase II inhibitors. Doxorubicin and daunorubicin were the first anthracyclines developed in the 1960s from bacteria. They intercalate DNA, inhibit topoisomerase and DNA synthesis, and generate free radicals causing DNA damage. Chronic cardiotoxicity is the main toxicity, with risk increasing with cumulative dose. Liposomal doxorubicin and mitoxantrone have less cardiotoxicity. Anthracyclines are used to treat many cancers but dose adjustments are needed for hepatic or renal dysfunction.
MDR T.B.
This document discusses multi-drug resistant tuberculosis (MDR-TB). It provides global and country-specific data on TB incidence and burden. MDR-TB is defined as disease resistant to at least two anti-TB drugs. Countries with high MDR-TB burdens are identified. The Indian scenario of TB is described, noting prevalence of MDR-TB in new and previously treated cases. A case study from Andhra Pradesh reports findings from 75 MDR-TB patients. Clinical factors promoting drug resistance and mechanisms of resistance are outlined. Treatment of MDR-TB and new chemotherapeutic agents are discussed. Global plans to combat TB, including targets and strategies, are summarized.
Leprosy
1) Lepra reactions are immunologically inflammatory states that can occur in leprosy patients. There are two main types - Type 1 reactions (downgrading and reversal reactions) and Type 2 reactions (Erythema Nodosum Leprosum or ENL).
2) Type 1 reactions involve the skin and nerves and cause swelling and tenderness. They occur after treatment begins. Type 2 or ENL reactions cause painful swollen skin lesions and other symptoms like fever. They typically occur after treatment in lepromatous patients.
3) Histologically, Type 1 reactions show edema while Type 2 reactions show deep inflammation, necrosis and few bacilli. Both can cause significant morbidity if not properly treated.
ART drugs ppt
structure of HIV, classification of ART drugs, newer ART drugs, MOA, Pharmacokinetics, adverse effects,
MDR-TB
This document discusses multi-drug resistant tuberculosis (MDR TB). It begins with an introduction to TB and definitions of key terms like MDR and XDR TB. It then describes first and second line anti-TB drugs, mechanisms of drug resistance, and factors contributing to acquired resistance. The document outlines methods for diagnosing drug resistance including genetic detection and drug sensitivity testing. It concludes with a brief overview of treatment approaches for MDR TB.
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describes the molecular basis behind the stage that controls the concept and application of immunotherapy in cancer management
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Pharmacotherapy of TB. Recommended regimen for TB under RNTCP(2016). New drugs under research and new targets.
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i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Monoclonal antibodies
Monoclonal antibodies are man-made versions of antibodies that are identical because they were produced by one type of immune cell. They can be designed to attack very specific parts of cancer cells. The main types used in cancer immunotherapy are naked monoclonal antibodies, conjugated monoclonal antibodies (attached to chemotherapy drugs or radioactive particles), and bispecific monoclonal antibodies (attached to two different antigens). Immunotherapy treatments that target immune checkpoint proteins like PD-1, PD-L1, and CTLA-4 have also shown promise in treating cancers. Non-specific immunotherapies like cytokines can generally stimulate the immune system to potentially help it better attack cancer cells.
Immune check point inhibitors and adverse effects
Immune checkpoint inhibitors can cause immune-related adverse events by removing inhibitory checkpoints and excessively activating the immune system. Common adverse effects include dermatitis in over 50% of patients, enterocolitis in under 20%, hepatitis in under 10%, and endocrinopathies. Symptoms usually onset several months after treatment. Management involves stopping the immune checkpoint inhibitor and administering corticosteroids in most cases. Life-threatening hyperimmunity is possible so consulting the oncologist and other specialists is important.
Chronic Lymphocytic Leukemia
The document discusses chronic lymphocytic leukemia (CLL), including its definition, epidemiology, etiology, pathogenesis, clinical symptoms, diagnosis, staging, prognosis, and treatment. Some key points:
- CLL is characterized by the proliferation and accumulation of small, mature lymphocytes in the blood, bone marrow, and lymphoid tissues. It most commonly affects elderly adults.
- Diagnosis is based on blood cell counts and immunophenotyping of lymphocytes. Prognosis depends on factors like clinical stage, genomic abnormalities, and biomarker expression levels.
- Treatment involves chemotherapy, chemoimmunotherapy, targeted therapies, and supportive care. The appropriate treatment approach depends on a patient's risk
Temozolomide
Temozolomide (TMZ) is an orally administered alkylating agent that is used as the first-line treatment for glioblastoma multiforme (GBM) due to its proven efficacy and good safety profile. TMZ works by methylating DNA at specific positions, and its cytotoxic effects require an intact DNA mismatch repair system and low levels of the DNA repair enzyme O6-methylguanine DNA methyltransferase. The standard dosing regimen for TMZ involves concurrent low-dose administration with radiation therapy followed by cycles of higher-dose adjuvant TMZ. Common side effects include nausea, vomiting, fatigue, and hematological toxicities.
Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by increased numbers of immature lymphocytes in the bone marrow. It is the most common cancer in children. Treatment involves chemotherapy given systemically and intrathecally in phases including induction, consolidation and maintenance to achieve and maintain remission. Prognosis depends on risk factors like age, white blood cell count, genetics. Late effects of intensive chemotherapy include secondary cancers, organ dysfunction. Relapse indicates poor prognosis requiring aggressive salvage therapies like stem cell transplant.
Methotrexate
Methotrexate is an antifolate drug that inhibits dihydrofolate reductase (DHFR), blocking the production of nucleotides needed for DNA synthesis. It is used to treat cancers like acute lymphoblastic leukemia as well as autoimmune diseases like rheumatoid arthritis. Methotrexate is transported into cells and polyglutamated, increasing its intracellular activity and half-life. It causes cell death by inhibiting DNA synthesis and inducing strand breaks. Resistance can develop through reduced polyglutamation, increased DHFR levels, or drug efflux pumps. The cytotoxic effects of methotrexate are S-phase specific and depend on drug concentration and duration of exposure.
Immunomodulators
This document provides an overview of immunomodulators. It begins with definitions of immunity and antigens. It describes the types of immunity and components of the immune system. It then discusses mechanisms of immunomodulation and how drugs can suppress or stimulate the immune response. The document focuses on clinically used immunomodulators, dividing them into immunosuppressants and immunostimulants. Several commonly used immunosuppressants are described in detail, including their mechanisms of action, uses, and toxicities.
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This document discusses the use of monoclonal antibodies for cancer therapy. It provides background on conventional chemotherapy and highlights limitations. It then covers the history and development of monoclonal antibodies, including their production and mechanisms of targeting cancer cells through antigen cross-linking, activating death receptors, or delivering cytotoxic agents. Specific examples of toxin-immunoconjugates and antibody-directed enzyme prodrug therapy are described. The monoclonal antibody Rituximab is discussed as the first FDA-approved therapeutic monoclonal antibody for cancer.
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Brentuximab vedotin .Reem Ibrahim
Brentuximab vedotin is an antibody-drug conjugate used to treat Hodgkin lymphoma and systemic anaplastic large cell lymphoma. It consists of the monoclonal antibody cAC10 linked to the microtubule inhibitor MMAE. When the antibody binds to CD30 proteins on lymphoma cells, the complex is internalized and MMAE is released, disrupting the microtubule network and causing cell death. Brentuximab vedotin allows targeted delivery of the cytotoxic agent to minimize side effects compared to conventional chemotherapy. Common side effects include neuropathy, nausea, fatigue, and low blood cell counts.
Brentuximab vedotin ..Reem Ibrahim
Brentuximab vedotin is an antibody-drug conjugate used to treat Hodgkin lymphoma and systemic anaplastic large cell lymphoma. It consists of the monoclonal antibody cAC10 linked to the microtubule inhibitor MMAE. When the antibody binds to CD30 proteins on lymphoma cells, the complex is internalized and MMAE is released, disrupting the microtubule network and causing cell death. Brentuximab vedotin allows targeted delivery of the cytotoxic agent to minimize side effects compared to conventional chemotherapy. Common side effects include neuropathy, nausea, fatigue, and low blood cell counts.
Cancer immunotherapy
Cancer immunotherapy uses the immune system to fight cancer. It stimulates the patient's immune system to attack and reject tumor cells. William Coley first observed in the late 1800s that some cancer patients who got infections after surgery saw their cancer improve. This led him to try treating patients by infecting them with bacteria, known as Coley toxins. Modern immunotherapy includes monoclonal antibody therapies like rituximab that target specific proteins on cancer cells, cancer vaccines, and cytokines to boost the immune system. Researchers are also exploring newer monoclonal antibodies and using cloned immune cells from patients to treat their cancer.
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- 2. Rituximab (MabThera™) is a mAb licensed for use in drug-resistant advanced follicular lymphoma and for diffuse large B-cell non- Hodgkin’s lymphoma in combination with other anticancer drugs. Rituximab
- 3. • Antineoplastic Agent, Anti- CD20 • Antineoplastic Agent, Monoclonal Antibody • Antirheumatic Miscellaneous • Immunosuppressant Agent • Monoclonal Antibody Classified as :
- 4. Rituximab is a monoclonal antibody that targets the CD20 antigen, which is expressed on the surface of pre-B and mature B-lymphocytes. After binding to CD20, rituximab mediates B-cell lysis (or breakdown). The possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity(ADCC).
- 5. Sequence of events leading to the depletion of circulating B-Lymphocytes by complement- dependent cell lysis, antibody-dependentcellular cytotoxicity, as well as apoptosis .
- 6. Rituximab belongs to the immunoglobulin G1 (IgG1) sub-class, consisting of a murine variable region (Fab region) and a human constant region (Fc region).
- 8. Dosage Forms Solution, Intravenous [preservative free]: Rituxan: 10 mg/mL (10 mL, 50 mL)
- 10. Side effects !!
- 16. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. This drug should be used during pregnancy only if the benefit outweighs the risk. AU TGA pregnancy category: C US FDA pregnancy category: C Rituximab Pregnancy Warnings