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OSCEazy Slide template 2021-2022 We look forward to your teaching session! • At OSCEazy, we have been renowned for our colourful slide templates and a very clear slide structure that presents information systematically • In this slide set there are slides for introductions, content, pictures, summaries...you can use as many or as few of these slides as you need by deleting/duplicating the template slides you want • We always advice to use a variety of different slide structures to keep your session engaging and interesting to look at! • You can add/replace content/pictures/textboxes to these slides as needed and delete any sections (such as this slide) as required **PLEASE DO NOT SHARE THIS SLIDE TEMPLATE OR USE THIS TEMPLATE FOR USES OTHER THAN YOUR TEACHING SESSION** • We would be very grateful to hear your feedback on our slide template. Please fill in this form once you have made your slides: https://docs.google.com/forms/d/e/1FAIpQLSdfFpHXn3QtY05WvPCqD_lq28lZoYnBRuk3jqCu8ORVKhSgAg/viewf orm?usp=sf_linkPreclineazy Toby and Meg ONCOLOGY HALLMARKS OF CANCER TREATMENT PHARMACOLOGY 16/05/2022 19:00HALLMARKS of CANCERHALLMARKS of CANCER Sustaining proliferative IMATINIB is an bcEpidermal Growth Factor receptor Foundin Chromic Myele.g. tyrosine kinase/HERS2 signalling / Growth oncogene from the tyrosine kinase results from the Philadelphia chromosome (a combination of 9 and 22 ). In health • Mitogen activated receptor (e.g. tyrosine kinase / HERS 2) • Activation of transduction cascade (inc RAS) • Cyclin D transcribed starting cell cycle Cyclin D In cancer RAS • Mutation in Epidermal growth factor receptor / RAS mutates to KRAS • Dysregulation of growth = inappropriate activation of cell cycle.HALLMARKS of CANCERHALLMARKS of CANCER Mutated tumour Evading growth suppression/ Maintaining growth suppressor Tumour suppressor e.g. RB In health Transcription • Cyclin Dependent Kinases (CDK) phosphorylate factor tumour suppressors when needed CDK • Tumour suppressors cannot bind/inhibit transcription factor • Transcriptionfor growth occurs when needed No inhibition In cancer • Mutation in tumour suppressor changing its shape. • Tumoursuppressor can never bind/inhibit transcription factor • Transcriptionfor growth occurs when not needed.HALLMARKS of CANCERHALLMARKS of CANCER Enabling replication immortality In health • Every cell division telomeres shorten • Cells have life cycle of around 40 division • Telomerestoo short and cell undergoes apoptosis Telomerase In cancer • Mutation turning on telomerase gene • Telomeraseenzyme transcribed and regenerated telomere • Unlimited divisionHALLMARKS of CANCERHALLMARKS of CANCER Invasion and Metastasis A characteristic cancer • Cancer cells must undergo Epidermal Mesenchymal transition (EMT) to be able to metastasis ( mesenchymal tissue is invasive and motile, epidermal tissue is not. Common metastasizing cancer? Melanoma easily metastasises Basal cell carcinoma rarely Where is this metastasis? metastasises. Left internal jugular nodeHALLMARKS of CANCERHALLMARKS of CANCER Inducting angiogenesis • Cancer masses will outgrow their blood supply leading to hypoxia. • Cancer cells release VEGF to cause angiogenesis Resistingapoptosis In health In cancer Caspase Activated • DNA mutated • P53 mutated • Damage detected • DNA damage not Bclproteins transcribed detected • P53 activated P53 detects • Bcl proteins transcribed • No apoptosis damage • Caspase activated • Caspase causes • >50% of cancers DNA damage have p53 mutation apoptosis HALLMARKS of CANCER Increased glucose uptake (and respire anaerobically) Deposition to cancer - BRCA1/2 (breast + ovarian cancer) - Lynchsyndrome (MSH gene) H.Pylori infection / Barrets oesophagus (both tumour suppressors) - Continued inflammation increases cancer risk/oesophageal HALLMARKS of CANCER Increased glucose uptake (and respire anaerobically) Deposition to cancer - BRCA1/2 (breast + ovarian cancer) - Lynchsyndrome (MSH gene) H.Pylori infection / Barrets oesophagus (both tumour suppressors) - Continued inflammation increases cancer risk/oesophageal Avoiding immune destruction In health • Immune system (CD8 cells) recognises CD8 cell viral, bacterial, cancer cells etc, as non self and binds via MHC I receptors In cancer Less expression • Cancer cells have fewer MHC I receptors Express PD-L1 of MHC I • Additionally, they express PD-L1 (programmed death ligand 1) which Cancer cell sends a signal to CD8 cells not to kill them Hormone receptors in breast cancer HER2 receptor Breast Cancer Treatment Letrozole Hormonal therapy Aromatase HER +ve Trastuzumab =Herceptin = HERS 2 receptor antagonist Androgens Oestrogen ER +ve Tamoxifen(pre menopausal patients) = Oestrogen receptor antagonist Letrozole (post menopausal) = Aromatase inhibitor Breast Cancer Treatment are important in the heart Hormonal therapy for repairing tissue. Aromatase HER +ve Trastuzumab =Herceptin = HERS can stop th c using 2 receptor antagonist Androgens Oestrogen ER +ve Tamoxifen(pre menopausal patients) = Therefore patients must have an Oestrogen receptor antagonist Letrozole (post menopausal) = Aromatase inhibitor TREATMENTS RADIOTHERAPY IMMUNOTHERAPY CHEMOTHERAPY High dose of radiation e.g. X-rays fired at cancer cells. Biological therapy that uses your own immune system to fight Good for relieving symptoms. Use of chemical substances to kill cancer cells. cells. e.g. Doxorubicin Side effects e.g. CAR-T - Alopecia Drugs acting on dividing cell Takesmonoclonal antibodies - Mucositis Cancer cells have a higher mitotic specific against cancer and - Skin damage rate so are targeted more combines it with T cells to fight - Nausea frequently. cancer. - Infertility Side effects - Mucositis - Nausea + vomiting - Myelosuppression (infection) - Bruising/bleeding - Alopecia - Infertilityhttps://www.grepmed.com/imag es/14290/pharmacology-toxicity- chemotherapy-adverse-oncology Chemotherapy and Interfere with DNA synthesis / replication Immunotherapy Drugs General - such as Breast, Leukaemia/Lymphoma Prostate colorectal, gastric PACLITAXEL TAXANE (stops CYCLOPHOSPHAMIDE- SIPULEUCEL-T microtubules polymerising in ALKYLATING AGENT anaphase) = Dentritic cell therapy where dendritic cells are cultured DOXORUBICIN - TOPOISOMERASE IMATINIB – bcr-abl tyrosine specifically (this is kinase inhibitor (specifically for immunotherapy) FLUROURACIL - ANTIMETABOLITE Chronic myeloid leukaemia treatment) Q U E S T I 1 N P53 is commonly mutated in Cance r. A AVOID APOPTOSIS How is this mutation advantageous to cancer cells? B ALLOWS LIMITLESS CELL GROWTH C AVASION OF IMMUNE SYSTE M D PROMOTES ANGIOGENESIS E UPREGULATED GLUT2 TRANSPORTERS ANSWER ON THE ZOOM POLL Q U E S T I 1 N P53 is commonly mutated in Cance r. A AVOID APOPTOSIS How is this mutation advantageous to cancer cells? B ALLOWS LIMITLESS CELL GROWTH C AVASION OF IMMUNE SYSTE M D PROMOTES ANGIOGENESIS E UPREGULATED GLUT2 TRANSPORTERS ANSWER ON THE ZOOM POLL Q U E S T I O N 2 A 32 year old man with Hodgkin A ALLOPURINOL Lymphoma is worried about on of his treatments which could damage his B BLEOMYCIN heart due to its cardiotoxic effects. C DOXORUBICI N Which of his treatments could he be D HERCEPTIN talking about? E METHOTREXATE ANSWER ON THE ZOOM POLL Hodgkin lymphoma treatment = doxorubicin (Adriamycin), Q U E S T I O N 2 bleomycin sulfate, vinblastine sulfate, and dacarbazine = ABVD • Allopurinol is used for gout (and to prevent tumour A ALLOPURINOL lysis syndrome) • Bleomycin causes pulmonary fibrosis B BLEOMYCIN • Herceptin is not used for Hodgkin lymphoma • Methotrexate causes pulmonary fibrosis/peripheral neuropathy/nephrotoxicity C DOXORUBICIN D HERCEPTIN E METHOTREXATE ANSWER ON THE ZOOM POLL Q U E S T I O N 3 A 55 year old post -menopausal woman A ASPIRIN has recently had surgery for a ER B VANCOMYCIN POSITIVE invasive ductal cell carcinoma. C TAMOXIFEN What treatment is best to prescribe after the surgery to reduce cancer D HERCEPTIN recurrence rate? E LETROZOLE ANSWER ON THE ZOOM POLL Q U E S T I O N 3 • Aspirin may reduce risk of metastasis but is not A ASPIRIN appropriate here. • Vancomycin could reduce post op infection (not B VANCOMYCON cancer recurrence) • Tamoxifen is an oestrogen receptor antagonist C TAMOXIFEN used for PRE -MENOPAUSAL women (although can be used post -menopausal in some cases) D HERCEPTIN • Herceptin is for HER2 positive (no mention of this) • Letrozole is for post menopausal women – E LETROZOLE aromatase inhibitor ANSWER ON THE ZOOM POLL Q U E S T I 4 N The Philadelphia chromosome is seen in A DELETION ON 7HCHROMOSOME Chronic Myeloid Leukaemia. It results B TRANSLOCATION ON 9TAND 22NDCHROMOSOME due to a chromosomal mutation. This enables the formation of bcr-abl TH ST C TRANSLOCATION ON 8 AND 21 CHROMOSOME tyrosine kinase oncogene. What is the chromosomal mutation D DELETION ON CHROMOSOME 8 E DUE TO EPIGENETICS Q U E S T I O4N • Deletion on chromosome 7 is cystic TH A DELETION ON 7CHROMOSOME fibrosis th nd B TRANSLOCATION ON 9HAND 22NDCHROMOSOME • 9 and 22 translocation is on chronic myeloid leukaemia C TRANSLOCATION ON 8HAND 21SCHROMOSOME (Philadelphia) • Chromosome 8 deletion I made up D DELETION ON CHROMOSOME 8 • Epigenetics refer to changes to DNA without a change to nucleotide. Not E DUE TO EPIGENETICS specific to a cancer but most cancers will have some epigenetic changes.Q U E S T I O 4 DELETION ON 7THCHROMOSOME A TH ND B TRANSLOCATION ON 9 AND 22 CHROMOSOME C TRANSLOCATION ON 8 TAND 21 STCHROMOSOME D DELETION ON CHROMOSOME 8 E DUE TO EPIGENETICS Q U E S T I 5 N Some cancer cells contain the PD -L1 A AVASIONOF THE IMMUNE SYSTEM receptor. What is the role of this receptor in B DEATH LIGAND ALLOWING IT TO KILL HEALTHY CELLS cancer cells ? C CD8 ANTAGONIST D DETECTS DNA DAMGE E INDEFINITE REPLICATION Q U E S T I 5 N PD-L1 sends a message to CD8 cells A AVASIONOF THE IMMUNE SYSTEM telling them not to kill its cell. It is NOT a CD8 antagonist B DEATH LIGAND ALLOWING IT TO KILL HEALTHY CELLS C CD8 ANTAGONIST D DETECTS DNA DAMGE E INDEFINITE REPLICATION PLEASE FILL OUT THE FEEDBACK FORM PLEASE TUNE IN TO OUR REMAINING SESSIONS THIS WEEK! @OSCEazyOfficial @osceazyofficial OSCEazy Osceazy@gmail.com