Module 2.2 Flashcards
1
Q
Aaliyah’s case study
A
- 59-year-old woman
- lives with partner in a small town in Ontario
- recently been feeling under the weather so booked doctors apt.
- doctor ordered a blood test
- revealed a diagnosis of iron deficiency anemia
- may be an indicator of gastrointestinal (GI) cancer in older men or post-menopausal women because of the frequent bleeding associated with these cancers
- so Gl cancer was a concern and she was referred to a gastroenterologist for testing
- additional testing to rule out the cancer
- An upper endoscopy was performed and a colonoscopy (lower endoscopy)
- Mass was found in the colon and taken for a biopsy
2
Q
Hyper proliferation of colorectal cancer
A
- cell has incurred one or more oncogenic mutations and begins to hyper proliferate.
- These cells grow and divide at a faster than normal rate.
3
Q
Adenomatous Polyp of colorectal cancer
A
- when the rapidly dividing mass of cells projects into the intestinal lumen, it is known as adenoma.
- Adenomas are often referred to as colonic polyps
4
Q
Precancerous polyp of colorectal cancer
A
- Pre-cancerous polyps can be removed before they become malignant.
- It may take 7-10 years for these growths to progress into the next stage, a malignant adenocarcinoma.
5
Q
Adenocarcinoma of colorectal cancer
A
- over time a polyp can become invasive and develop into an adenocarcinoma which is the most common type of colorectal cancer.
- The transition is when the cells invade into the adjacent tissue layers
6
Q
Advanced colorectal cancer
A
- if polyps go undetected, they will continue to grow and further invade deeper tissue layers.
- The cancer may enter the bloodstream and metastasize to other parts of the body
7
Q
Colorectal cancer statistics
A
- third most common cancer in Canada
- second most deadly
- About 26,300 people are diagnosed with and about 9,500 people die from colorectal cancer in Canada each year
8
Q
Screening for Colorectal Cancer
A
- Most effective way to reduce the burden of cancer
- It is estimated that screenings have reduced the risk of colon cancer by 77%
- Screenings are done on patients that have an elevated risk due to age and family history of colorectal cancer
8
Q
The Impact of Colorectal Cancer on different populations
A
- mortality and ioncidences is higher for first nations in ontario
- second most common diagnosed for first nations people and third for non first nations
- marginalized communities have higher rates of non-infectious diseases like cancer
- Incidence rates among long-term Canadian residents are higher than new immigrants.
- The incidence rate increases for colorectal cancer the longer you reside in Canada, making diet an important cancer risk factor
9
Q
The fecal immunochemical test and colonoscopy
A
- safe and painless at home screening test
- Examines stool for tiny amounts of blood which could be caused by colorectal cancer or precancerous polyps
- Taken by 50-74 y/o every 2 years.
- If these tests are abnormal, patients get a colonoscopy
– Recommended screening test for those with increased rates of developing colorectal cancer
10
Q
hemicolectomy for colorectal cancer
A
procedure that removes the cancer and the surrounding lymph nodes that drain the area where the tumour is located
11
Q
Histology
A
- Histology is used to look for changes to normal tissue structure, and use this info to determine the extent of tumour progression.
- Histology slides are created by cutting and staining thin sections of a specimen and then viewing them under a microscope.
- Majority of colorectal cancers are (adeno)carcinomas
12
Q
Aaliyah’s story: Histology
A
Pathologist determined that the cancer invaded into deeper tissue layers but had not reached the outer border of the tissue
13
Q
Characterizing Solid Tumours: stage
A
T: depth of tumor invasion
N: spread to the lymph nodes
M: metastasis of the cancer to other parts of the body
- Pathologists examine histology slides to provide a score for T and N. This with the presence/absence of metastasis for an overall stage
- Lower numbers indicate lower degree of cancer progression and better patient outcomes
14
Q
Characterizing Solid Tumours: grade
A
- Grade of cancer is based on how abnormal the cells in the biopsy, or tumour appear compared to normal cells in that tissue.
- A grade (G) is give from 1-4 higher the grade, more abnormal the cancer cells that are present in the sample, and poorer the prognosis
15
Q
Normal cells
A
known as glands in the colon. Cells appear hollow on the inside, larger glands have space in the middle
16
Q
G1 tumour
A
- all cancer cells still form glands,
- glands are less circular
hollow appearance of cells is lost - cells may grow into central space.
17
Q
G2: (medium grade)
A
some gland formation still visible
Additional loss of circular gland structure
Cell shape drastically different
Central glad space occupied by cells or debris from necrosis
18
Q
G2: (medium grade) tumour
A
- some gland formation still visible
- Additional loss of circular gland structure
- Cell shape drastically different
- Central glad space occupied by cells or debris from necrosis
19
Q
Sporadic colorectal cancer
A
somatic mutations occur spontaneously on both alleles of the adenomatous polyposis coli gene
19
Q
G3: (medium-high grade) tumour
A
- Very little gland formation present
- Cells vary in shape and size
- Only a few cells continue to exhibit their normal hollow appearance
20
Q
G4: (High grade) tumour
A
- Gland structure practically non existent
- No trace of the original hollow cell appearance or central space
- Instead, cells have no specific structure
21
Q
Familial colorectal cancer
A
characterized by inherited mutation. Most common include mutations to one of the mismatch repair genes such as MSH2.
22
Q
Lynch Syndrome
A
- Lynch syndrome aka Hereditary nonpolyposis colorectal cancer syndrome is the most common hereditary colorectal cancer syndrome,
- accounts for 2-4% of all colorectal cancers
- Caused by germline mutation in DNA mismatch repair gene.
- Since one copy of the gene is already mutated, it only takes one more acquired mutation in the second copy of MSH2 to develop cancer
- People with lynch syndrome are at increased risk of developing many different types of cancer
23
Developing a Prognosis: Age and General health
- for instance, survival is lower amongst older patients and those that are obese
24
Developing a Prognosis: Response to treatment
- tumours responsiveness to the treatment is a determinant of prognosis.
- For example, colorectal cancers with certain mutations are less responsive to available treatments.
25
Developing a Prognosis: Stage and grade
- For colorectal cancer diagnosed at stage one, there is 90% survival while at stage 4, its 10%
26
Developing a Prognosis: Genetics
- type of mutation causing the cancer impacts the prognosis. - For example, there are specific colorectal cancers caused by a specific known gene mutation that lead to more aggressive cancers, leading to poorer prognosis.
27
Developing a prognosis: Access and compliance
This impacts prognosis as in Ontario 10% more of metis women are overdue for colorectal cancer screening, suggesting delayed detection and poorer prognosis.
28
Jorges story
- 37 yo male
- shortness of breath and overall lower energy levels
- Came to emerge with a nosebleed that hasn't stopped for two days and an intermittent fever over the last week
- Indicative of: blood disorder, infection, or cancer.
- Emergency physician admits him into hospital to get a blood test
- test show low hemoglobin, high white blood cells, high percent blasts and low platelets
29
Introduction to Blood Cancers
- Unlike solid tumours like breast, lung or colorectal cancer, blood cancers are not typically diagnosed by body imaging.
- malignant cells are first detected in a patient's blood
- These cancers begin in the bone marrow when rapidly growing blood stem cells fail to mature into the healthy functioning blood cells our bodies need.
- Instead produce more cancer cells and eventually crow out the normal stem cells
- These types of changes in cell population often result in fatigue due to decreased red blood cells providing insufficient oxygen, immune issues due to a lack of different forms of white blood cells, and bleeding and clotting issues due to a loss of platelets
30
Impact of blood cancers in canada
- 10% of cancer diagnoses in Canada, with 21,000 new diagnoses in 2019
- First nations people have lower incidence of blood cancers compared to non-first nations people in Ontario.
- but first nation people have a lower survival rate from blood cancers
31
Hematopoiesis
Development of mature blood cells from hematopoietic stem cells in the bone marrow
32
Hematopoietic Stem Cells
- make up a small portion of the cells in the body; about 11-22 thousand out of the trillions of cells in the human body.
- Have long lifespans upwards of several years while specialized cells only live weeks to months
- Unspecialized and can differentiate into progenitor cells which give rise to specialized cells
32
Common myeloid Progenitor & Common Lymphoid Progenitor
- are multipotent
- Potential to differentiate into only a subset of specialized blood cell types
- Common myeloid progenitor cells replace specialized cells that are damaged or lost which produce immature cells called blasts that eventually develop into fully differentiated specialized cell types
33
Specialized Myeloid Cells
- Myeloid progenitor cells differentiate into specialized myeloid cells such as red blood cells, platelets, and specific types of white blood cells
- Unlike HSCs and Myeloid progenitor cells these are highly specialized and have specific capabilities
34
Specialized Lymphoid Cells
- Common lymphoid progenitor cells differentiate into few specialized lymphoid cells such as T-cells, B-cells and natural killer cells
- Unlike HSCs or common lymphoid progenitor cells, these are highly specialized and have specific capabilities
35
Hematopoiesis and Blood Cancer
Blood cancers arise when HSCs rapidly proliferate and fail to fully differentiate into more specialized cells.
- When HSC progenitors aren't fully differentiated, they are known as immature cells or ‘blasts’ and don't have the full capability to perform their specialized cell functions
36
Differentiation Block
- Tumour suppressor gene that's involved in cell differentiation is lost in the HSCs or the common progenitors.
- leads to initial accumulation of immature blood cells, or ‘blasts’
37
Enhanced Proliferation
- at some point, another gene is mutated in these cells; this time a proto-oncogene that produces growth signals.
- This result is a major increase in proliferation
38
classical blood cancer pathway
Differentiation Block and Enhanced Proliferation
- when both occur malignant blasts crowd out normal HSC's and produce the symptoms associated with disease progression
39
4 types of leukemia
1) Acute lymphocytic leukemia
2) Chronic lymphocytic Leukemia (CLL)
3) Acute myeloid leukemia (AML)
4) Chronic myelogenous leukemia (CML)
40
Acute leukemia
- AML, ALL
- Characterized by proliferation of poorly differentiated cells
- Usually progresses rapidly
- Immediate treatment is usually required
- Immature cells with more open nuclear chromatin
41
Chronic Leukemia
- CML, CLL
- Characterized by proliferation of well-differentiated cells
- Usually progresses slowly
- May be monitored for some time before treatment is initiated
- Mature cells with more clumped nuclear chromatin
42
Myeloid leukemia
- One of the myeloid progenitors becomes malignant.
- When progenitors allow the formation of mature cells and grow slowly, this is known as chronic myeloid leukemia.
- When progenitors to myeloid cells grow rapidly and partially or fully lose the ability to form mature cells, this is known as acute myeloid leukemia.
- Tend to be less differentiated in blasts than in leukemia
43
Lymphoid leukemia
- If the leukemia is lymphocytic, the cancer arises from a lymphoid cell origin
In ALL, malignant undifferentiated blasts grow quickly.
- Common progenitor of all or most lymphocytes that becomes malignant
CLL is a slow growing and more differentiated malignancy.
- Normally more differentiated malignant blast cell leading to a specialized lymphoid cell
44
Prognostic Factors for Leukemia
- In Canada, the overall five-year survival rate for leukemia is about 60%
- Age: over 65 yo have the highest mortality.
- Childhood leukemia have about 90% survival rate
- Weight: people with a normal BMI at diagnosis or during treatment have significantly higher survival rate
- Previous Blood Disorders: medical history of anemia, hemophilia or other blood disorders have a less favourable prognosis
- Genetics: some specific mutations can cut leukemia survival odds by half while others can raise them to near 100%
45
AML and Chromosomal Translocations
- chromosomes may break and be fused together wrong called translocation
- the break can occur between two gene sequences
- fusion causes hybrid sequence that codes for fusion protein
eg.
- PML-RARA, which occurs during a fusion of chromosomes 15 and 17 at the sites of the PML and RARA genes.
46
Normal RARA
- The normal RARA gene codes for the RAR-α protein.
- Under normal conditions, when healthy HSCs receive a signal to produce more myeloid cells, RAR-α is temporarily inactivated to allow differentiation to take place
46
what do fusion genes have the potential of being?
oncogenes
47
PML-RARA Fusion
- When a PML-RARA fusion takes place, RAR-α no longer needs to respond to differentiation signals, leading to an accumulation of immature blasts
48
ATRA Treatment (ALl-trans retinoic acid)
- The effects of PML-RARA on white blood cell differentiation can be effectively reversed by treatment with ATRA.
- ATRA treatment specifically acts on blast cells, causing them to mature into normally-functioning specialized myeloid cells.
49
future of cancer care
- research has rapidly progressed in last decade, causing important discoveries
- new technologies have emerged making screening better
- Clinical cancer management is also rapidly evolving to be more patient-centered and holistic, emphasizing the importance of mental health and palliative care support
- Changes are helping create a patient journey experience that is accessible and adaptable to all individuals
50
biomarkers
- Gene expression is a type of biomarker.
- In cancer, biomarkers have important implications in screening (e.g. Lynch syndrome) and treatment options (e.g., PML-RARA translocation)
- Cancer research leads to a better understanding of cancer biology and to the development of new medicines.
- list of cancer biomarkers tested grows almost annually.
51
6 biomarkers
- Small chemical products
- Enzymes
- DNA
- RNA
- Cancer cells
- Protein
52
Diagnostic Biomarker
detects or confirms the presence of a disease
53
Prognostic Biomarker
indicates the likelihood of disease progression or recurrence
54
Predictive Biomarker
Predict the response to a particular treatment
55
Human genome project
- complete human genome was first sequenced in 2001.
- Took 13 years and over $1 billion USD
56
Next-gen sequencing
genome sequencing costs under $1000 USD and can be completed in hours to days
57
Tumour sequencing
Scientists now have access to ever-increasing databases of genomic information
58
Data analysis of Advances in Gene Sequence and Cancer Treatment
- Databases can be used to identify previously unknown biomarkers and common mutations in certain cancers allowing the cancers to be characterized quickly
59
Common screening tools for cancer
- Pap smears for cervical cancer
- Mammograms for breast cancer
- Digital rectal exams for prostate cancer
- FITs and colonoscopies for colorectal cancer
60
most common treatments for cancer
- Surgery
- Radiation
- Chemotherapy
- Immunotherapy
61
how can cancer treatment become more complicated?
- if a patient lives far from a cancer centre, and must travel for treatment and be away from their support group of friends and family for extended periods
