Block C Lecture 1 - Basics of Cancer and Therapeutic Targets Flashcards
What is cancer?
A term which describes a group of diseases which are characterised by the uncontrolled growth and division of abnormal cells within the body. These cells can invade surrounding tissues and spread to distant parts of the body, disrupting bodily functions
(Slide 3)
What is the difference between benign and malignant tumours?
Benign tumours grow locally and don’t invade adjacent tissues whereas malignant tumours invade nearby tissues and metastasise
(Slide 4)
What does the term “metastasise” refer to?
When cancer cells spread from the original (primary) tumour site to other parts of the body, forming secondary tumours.
(Slide 4)
What 2 continents have the highest proportion of cancer deaths compared to their incidence?
Asia and Africa
(Slide 5)
What 2 ways are cancerous diseases described / characterised by?
The organ in which they originate from
The cell type in which they originate from
(Slide 6)
How does cancer arise?
From the accumulation of mutation in genes which control growth and proliferation of cells (such as oncogenens and tumour suppressor genes) - leading to altered gene expression
(Slide 8)
What are 3 examples of genes which can cause cancer if they experience mutations?
Tumour suppressor TP53 gene
RB1 gene
BRCA1/2 genes
APC gene
PTEN gene
CDKN2A gene
SMAD4 gene
Oncogenes
KRAs genes
BRAF gene
HER2 (ERBB2) gene
EGFR gene
MYC gene
ABL1 gene
PIK3CA gene
ALK gene
Note: We probably don’t have to know these specifically (other than maybe tumour suppressor TP53 and oncogenes in general), but it will definitely be useful for extra marks in essay questions
(Slide 9)
How can mutations in oncogenes or tumour suppressors lead to different protein expression in cancer cells?
Oncogenes - mutations can result in a mutant protein or the overproduction of the wildtype protein in cancer cell compared to normal cell
Tumour suppressors - the protein is silenced in cancer cell
(Slide 10)
What are 2 examples of conditions which can increase the risk for cancer 5-10%? (bonus points for saying which cancer).
Answers Include:
Xeroderma Pigmentosum - Skin cancer
Wilm’s tumour - Kidney cancer
Familial adenomatous polyposis - colon and rectum cancer
BRCA 1/2 - breast and ovarian cancer
(Slide 11)
What is a somatic mutation?
A mutation which occurs after conception, however they can (but don’t always) occur before birth
(Slide 12)
What are 3 examples of types of somatic mutations which can lead to cancer?
Single base change mutations
Additions
Deletions
(Slide 12)
Why does the chance of cancer occurring increase over time?
As cancer is a multi-stage process which is caused by the accumulation of multiple mutations, not just a single one.
The more time that passes, the higher the chance of these mutations randomly occurring, if just a single mutation caused cancer then the appearance of it would be more sporadic, sudden and seemingly random
(Slide 13)
What chromosome is found in most chronic myeloid leukaemia (CML) patients, and how is this formed?
The Philadelphia (Ph) chromosome, which is made due to a translocation between chromosomes 9 and 22
(Slide 14)
Does the site of chromosomal breaking and re-joining in CML patients change between different cells in the patients and / or different patients?
The site is identical in all cells in a particular patient, however it differs between patients
(Slide 14)
What is the definition of the “hallmarks of cancer”?
Biological capabilities which are acquired as a result of mutations which occur during the development of cancer, which enable tumour growth, survival and metastasis
(Slide 16)
What are 7 examples of the hallmarks of cancer?
Answers Include:
Tumour-promoting inflammation
Limitless replicative potential (known as immortality)
Evasion of apoptosis
Genomic instability
Tissue invasion and metastasis
Sustained angiogenesis (process of forming new blood vessels)
Self-sufficiency in growth signals
Reprogramming of energy metabolism
Insensitivity to anti-growth signals
Evasion of the immune system
(Slide 16)
How can cancers become more heterogenous as they progress?
As at each stage of progression, some individual cells can acquire an additional mutation or epigenetic change which gives it a selective advantage over neighbouring cells, which makes it better able to thrive in its environment
(Slide 17)
What does the term “tumour grade” describe?
The aggressiveness of the tumour, likelihood of metastasis, the response to the treatment and prognosis
(Slide 19)
What does the term “tumour stage” describe?
The extent of the disease, likelihood of metastasis and the treatment decision
(Slide 19)
What do DNA / molecular profiles allow?
For treatment to be tailored to specific patients
(Slide 19)
What are the 4 types of breast cancer?
Ductal carcinoma in situ (DCIS) (non-invasive)
Invasive ductal carcinoma (IDC)
Lobular carcinoma in situ (LCIS) (non-invasive)
Invasive lobular carcinoma
(Slide 20)
What does in situ mean?
In the natural / original position or place
(Slide 22)
What are the grades in the Bloom Richardson grading system for breast cancer and what are the requirements for these?
Criteria focusses on the degree in which the tumour retains normal glandular structure
Grade 1 - 75% of tubules (well differentiated)
Grade 2 - 10-75% of tubules (moderately differentiated)
Grade 3 - <10% of tubules (poorly differentiated)
(Slide 21)
What does TNM stand for in reference to the TNM staging system in breast cancer?
T - tumour size and extent of spread in the breast
N - lymph node involvement
M - metastasis (spread to distant organs)
(Slide 22)
What are the grades in the TNM staging system for breast cancer and what are the requirements for these?
T0 - No evidence of primary tumour
Tis - Carcinoma in situ
T1 - Tumour is < or equal to 2 cm
T2 - Tumour is between 2 and 5 cm
T3 - Tumour is bigger than 5 cm
T4 - Tumour has grown into the chest wall / skin
(Slide 22)
What are the 4 molecular subtypes which breast cancers are split into and what is this based on?
Triple negative, Her2+, Luminal A and Luminal B. This is based on protein expression profiling
(Slide 23)
What is protein expression profiling?
The systematic analysis of all the proteins expressed in a cell, tissue, or organism under specific conditions. It helps in understanding biological processes, disease mechanisms, and drug responses.
(Slide 23)
What are receptor expression, histologic grade, prognosis and medical therapy of the triple negative subtype of breast cancer?
Receptor expression: None (negative for HER2, ER and PR)
Histologic grade: High (grade III)
Prognosis: Poor
Therapy: Chemotherapy
(Slides 23 and 25)
What are receptor expression, histologic grade, prognosis and medical therapy of the HRE2+ subtype of breast cancer?
Receptor expression: HER2
Histologic Grade: High (grade III)
Prognosis: Poor (but not as bad as triple negative)
Therapy: Chemotherapy which is usually combined with HER2-targeted therapy (like Trastuzumab)
(Slides 23 and 25)
What are receptor expression, histologic grade, prognosis and medical therapy of the Luminal A subtype of breast cancer?
Receptor Expression: ER+ (estrogen receptor) or PR+ (progesterone receptor), and HER2-negative
Histologic Grade: Low (grade I)
Prognosis: Good
Therapy: Endocrine therapy (primary), such as tamoxifen (pre-menopausal women) or aromatase inhibitors (such as letrozole or exemestane (post-menopausal women), chemotherapy, or CDK4/6 inhibitors for advanced or metastatic cases
(Slides 23 and 26)
What are receptor expression, histologic grade, prognosis and medical therapy of the Luminal B subtype of breast cancer?
Receptor expression: ER+/PR+, can be HER2 positive or negative
Histologic Grade: Intermediate to high (Grade II/III)
Prognosis: Good (but not as good as luminal A)
Therapy: Endocrine therapy (aromatase inhibitors such as letrozole or anastrozole, or tamoxifen can be used for ER+/PR+ tumours), HER2-targeted therapy such as trastuzumab if HER2 is expressed, or chemotherapy
(Slides 23 and 26)
What is the most common molecular subtype of breast cancer?
Luminal A (~40% of cases)
(Slide 23)
What is the trend between the 5 year survival rates of the 4 stages of breast cancer, and what does this tell us?
Stage 1 and 2 have relatively high rates (99 and 90% respectively), but there is a big drop off to 60% for stage 3 and an even bigger drop off to 15% for stage 4
Cancer should be caught early to ensure a high chance of survival
(Slide 24)
Why is chemotherapy rarely required in luminal A breast cancer?
Due to the less aggressive nature of these tumours
(Slide 26)
