Cancer immunology including hallmarks of cancers, the causes, clinical symptoms, risk factors, diagnosis and treatments of colorectal cancer and leukemia.
2. What is cancer
● Malignant growth of tumour resulted from uncontrolled division of
abnormal cells
Source:
http://arunnanomedicine.blogspot.com/2015/10/cell-d
ivision-and-cancer.html
3. Hallmarks of cancers
● Self-sufficiency in growth signals
● Insensitive to anti-growth signals
● Evade apoptosis
● Limitless replicative potential
● Angiogenesis
● Tissue invasion and metastases
● Evade immunosurveillance
Sourced from:
The Hallmarks of Cancer the next generation
5. Leukemia
● Cancer that originates in bone marrow - affects lymphatic system
● Various risk factors
● Killed 281,500 people in 2010
● Symptoms-
○ Fatigue
○ Fever
○ Enlarged spleen
○ Increased susceptibility to infection
Source:
http://whataboutblood.com/index.php/2017/10/08/what-is-leukemia/
8. P53 Protein
● “Tumor Suppressor”
● Highly polymorphic
● Prevention of altered DNA being
replicated in cell division leading to
tumor
● Triggered by cellular stresses such as the
presence of oncogenes
● Monitors the cell cycle - prevent cell
becoming tumor cell
● Works with MDM2 protein and p14ARF Source:
https://www.123rf.com/photo_18482715_ribbon-mod
el-of-p53-protein-bound-to-dna-molecule-p53-aka-tu
mor-protein-53-is-a-transcription-factor.html
10. P53 Mutation
● One of the most common
cancer causing mutations
● Commonly occur at R248
and R273
● Commonly in p53, less
commonly in MDM2 and
p14ARF
● Polymorphism leaves
susceptibility to mutation
12. Colorectal Cancer
● Third most commonly diagnosed cancer
(1.36 million) after lung (1.82 million) and
breast cancer (1.67 million)
● Malignant transformation of normal
colonic epithelial cells
Source: Mayo Clinic
Proceedings
Source:
http://www.thepinsta.com/tumor-progression_Q9aB3pb%7CRnAX3hnV6K7CaiPPmF%7CHThDf%7CvLIGTXPGm
g/
13. Industrialized countries as high-risk regions
Table 1: Top 15 countries with highest rate of colorectal cancers for both sexes in 2018
Source:
World Cancer Research Fund,
14. Risk factors
● History : colorectal cancer, polyps
● Bile inflammations: ulcerative colitis, Crohn’s diseases
● Polyposis syndrome: familial adenomatous polyposis (FAP), hereditary
non-polyposis colorectal cancer (HNPCC) or Lynch syndrome
● Age: >50 years old
● Gender: man
● Cigarette smoking
● Diet: high red meat consumptions, low-fibre intakes
● Obesity
Lynch syndrome
Source:
http://www.murrasaca.com
/english/colon-cancer.html
Source: Genetics home
reference
15. Genetic instability promotes carcinogenesis
● Microsatellite instability (MSI):
Impaired DNA mismatch repair (MMR)
Source:https://coolscienceforyou.wordpress.com/2
014/01/18/cancer/
Source:https://biodiscovery.pensof
t.net/article/8961/
Source:https://www.omicsonline.org/article
s-images/JBABM-04-e108-g001.html
● CpG island methylator phenotype (CIMP):
Gene silencing
Three pathways:
● Chromosomal instability (CIN):
APC tumour suppressor and KRAS
gene mutations, other mutations
(eg: TGF-β)
16. Serrated polyps as pre-malignant polyps
● Hyperplastic polyps (HPs): polypoid lesion, left colon
● Sessile serrated adenomas/polyps (SSA/Ps): flat lesion, right colon
● Elongated crypts and a saw-toothed pattern of the crypt epithelium
Source:Oncology Reports
17. Symptoms
● rectal bleeding (angiogenesis)
● bowel habit alterations
● weight loss
● abdominal pain
● constipation
● diarrhoea
* * Depends on locations of tumour and
can vary among individuals
Source:
https://www.slideshare.net/csbr
prasad/git-8csbrp
Source: http://kimajafarwani.blogspot.com/2016/12/colorectal-cancer-colorectal-cancer.html
19. Diagnosis of Leukemia
● Physical examination : swollen lymph nodes
● Blood cell count : High leukocyte levels
● Biopsy: Bone marrow and Lymph nodes
Tissue Biopsy
Source:
http://whataboutblood.com/index.php/2017/10/08/wha
t-is-leukemia/
Source: https://globalnews.ca/news/3805664/boosting-fat-cells-in-bone-morrow-suppressed-cancerous-leukemia-cells-study/
20. Diagnosis of colorectal cancer
Source:
https://www.medicinenet.com/colonoscopy
/article.htm
● Fecal blood test
● Colon and rectum biopsy
● Colonoscopy
Source:
https://www.123rf.com/photo_82039984_stock-vector-fecal-o
ccult-blood-testing-vector-illustration.html
21. Newer diagnostic approaches
● Biomarkers – a molecule which can be associated with disease
KRAS mutation in
colorectal cancer
Source: https://www.lungcancerdreamteam.org/kras-lung-cancer/the-kras-mutation/
22. Newer diagnostic approaches
● Biomarkers – a molecule which can be associated with disease
KRAS mutation in
colorectal cancer
Source: https://www.lungcancerdreamteam.org/kras-lung-cancer/the-kras-mutation/
24. Treatment of Cancer is a diverse as the range of
cancers
● Chemotherapy
○ Chemicals to kill or inhibit growth of
cancer cells
● Radiation therapy
○ Ionising radiation to kill or inhibit
growth of cancer cells
● Surgery
○ Removal to cancerous tissue or
tumours
● Hormone therapy
○ Chemicals that block or inhibit
hormones that stimulate cancer cell
growth
● Targeted Therapy
○ Drugs that target specific features of
cancers cells to stop their growth or
spread
● Stem cell/bone marrow
transplant
○ Restoring the source of erythrocytes
and leukocytes (can follow chemo and
radiation)
● Immunotherapy
○ Uses immune system agents to treat
cancer and stimulate greater immune
responses
25. Treatment of Cancer can cause damage to the body
● Heart
○ Weakened heart muscles
○ Arrhythmia
○ Coronary heart disease
● Lungs
● Endocrine system
○ Infertility
○ Osteoporosis
○ Hot flashes
● Joint, bone and soft tissue
○ Pain
○ Osteoporosis
○ Rheumatological issues
● Nervous system
○ Hearing loss
○ Increased risk of stroke
○ Damage to Peripheral Nervous
system
● Surgery issues
○ Removal of key immune system
organs
■ Spleen
■ Lymph nodes
○ Phantom limb pain
26. Monoclonal antibodies are produced from a single
B cell lineage and initiates four pathways
● Single
● Generated from a “factory” cell
● Stimulates (classification by function)
○ Disturbing rumour cell signalling
○ Complement dependent cytotoxicity
○ Antibody dependent cellular cytotoxicity
○ Activation of Adaptive immune system
27. Monoclonal Antibodies for leukemia and colorectal
cancer
● Colorectal Cancer
○ Vascular endothelial growth factor
(VEGF)
■ bevacizumab
○ Epidermal growth factor receptor
(EGFR)
■ Cetuximab
■ panitumumab
● Leukemia
○ CD33
■ Gemtuzumab
○ CD52
■ Alemtuzumab
28. Summary
● Cancer
○ can be defined by the 10 hallmarks
● Leukemia
● Colorectal Cancer
● Diagnostic biomarkers could be used for cancer detection
● Treatment
○ Tailored
○ Some treatments can cause other side effects
○ Immunotherapy: Monoclonal antibodies