Cancer and Inflammation PDF

Cancer and inflammation Dr Katie Finegan ILOs Understand how inflammation and cancer are intrinsically linked. Understand how targeting cancer-associated inflammation is a therapeutic approach in cancer Apply knowledge of cancer and its relationship to inflammation, to identify sympto...

Cancer and inflammation Dr Katie Finegan ILOs Understand how inflammation and cancer are intrinsically linked. Understand how targeting cancer-associated inflammation is a therapeutic approach in cancer Apply knowledge of cancer and its relationship to inflammation, to identify symptoms that may be indicative of cancer. Understand how this identification of cancer "red flag" symptoms is integrated into clinical practice. Cancer in the UK What makes a cancer cell different? MUTATIONS THESE HAPPEN ALL THE TIME WE ARE VERY WELL EQUIPPED TO DEAL WITH THEM What makes a cell cancerous? Tumour-promoting inflammation Inflammation can support all aspects of cancer Initiation Growth Metastasis Response to therapy  Inflammation: cancer initiation Chronic inflammation Tumour promoter : initiates tumour formation Causes genetic instability: genetic mutations Exploits existing mutations (oncogenes) “Two-hit” hypothesis Single oncogene/tumour suppressor mutation = no tumour Multiple genetic mutations = tumour Inflammation = no tumour Inflammation + single mutation = tumour  Inflammation: tumour growth chemokines Immune cells Positive feedback loop between immune Immune cells can produce factors to cells and tumour cells encourages tumour support all facets of tumour progression progression  Inflammation: metastasis Pro-tumourigenic inflammation supports Degradation of the ECM Intravasation Formation pre-metastatic niche Attraction to the metastatic site Extravasation Growth and development of metastases  Expanded hallmarks of cancer https://www.frontiersin.org/articles/10.3389/fevo.2021.661583/full  Anti- tumour immunity (inflammation) https://www.researchgate.net/figure/Anti-tumor-immune-response-1-Notes-DCs-process-and-present-tumor-antigens-on-MHC_fig1_320750140  Balance of pro and anti-tumour immunity https://www.researchgate.net/figure/Anti-tumor-immune-response-1-Notes-DCs-process-and-present-tumor-antigens-on-MHC_fig1_320750140 Inflammatory risk factors for cancer Obesity Smoking Alcohol consumption Chronic inflammatory disease Genetics CANCER CAUSATION Obesity Inflammatory signalling and cancer Inflammation and cancer TARGETING INFLAMMATION FOR CANCER THERAPY  Chemotherapy Chemotherapy prevents cell growth PROBLEM: Some normal tissues also have rapid cell growth hair loss weakened immune system - infection prone sickness and diarrhoea  Targeted therapies: Inflammation Tumour-promoting inflammation Inflammation can support all aspects of cancer Initiation Growth Metastasis Response to therapy  Targeted therapies: Inflammation Two ways in which we can target inflammation in cancer 1.Inhibit pro-tumour inflammation 2.Promote anti-tumour inflammation  Targeted therapies: Inflammation 1. Inhibiting pro-tumour inflammation Signalling pathways highlighted in red boxes are targets for “signal-inhibitors “ or inflammation-targeted therapy Blocking these pathways prevents pro-tumourigenic inflammatory signalling within the tumour Example: B-raf inhibitors such as Dabrafenib  Immunotherapy Promoting anti-tumour inflammation Checkpoint approach T cell immune responses (anti-tumour) are controlled through on and off switches, so called 'immune checkpoints' These protect the body from potentially damaging immune responses Developed drugs to target these immune checkpoints This illicits anti-tumour T-cell-mediated immune responses e.g. anti-CTLA4 and anti-PD1 or PDL1 therapy CANCER RED FLAGS  What is a red flag in Pharmacy practice? A red flag is a symptom or presentation that could be indicative of serious disease Very important aspect of Pharmacy Practice – frontline patient facing role of pharmacists In terms of cancer red flags are symptoms that suggest a patient has cancer When considering red flag symptoms or their severity, must get a full picture of the patient Other underlying risk factors Patient information  Assessing cancer red flags Duration — when do harmless symptoms become red flags? Clinical complaints such as cough, tiredness or diarrhoea are common in acute, self-limiting viral illnesses but can transform into red flag symptoms should they persist. The precise period varies, but the upper limit is usually around 4–6 weeks; Demographics — age is an important determinant of cancer risk. Symptoms that are viewed as red flags in older age groups may be more likely to be caused by other diagnoses in younger age groups where that particular type of cancer is rare.  Assessing cancer red flags Clinical features — anything presenting as ‘not normal’ for the patient should be considered. For example, a lump (in particular lymph nodes — lymphadenopathy) or mass, a mucosal abnormality (in particular, oral or rectal), unexplained bleeding (in particular, vaginal, rectal or bruising). Red flag symptoms necessitating referral - examples Lung red flags Age 40 years and over with: Persistent cough for more than three weeks; Recurrent chest infections; Coughing up blood; Repeat purchases of cough medicine. Oral red flags Red and white patches, and ulcers that do not heal within three weeks; An unexplained lump in the neck, on the lips or in the mouth.