cancer Flashcards
what is cancer?
A disease caused by normal cells changing so that they grow in an uncontrolled way, invade surrounding tissue and travel to other parts of the body (metastasis)
malignant neoplasm’, ‘malignant tumour’
what is Aetiology
the cause, set of causes, or manner of causation of a disease or condition.
why do tumours arise?
- Accumulation of genetic alterations (e.g. mutations, deletions, translocations)
- Epigenetic changes (e.g. promoter methylation) in cells.
what causes changes in the DNA which cause cancer
Inherited
External factors e.g. smoking, diet, UV irradiation, pollutants, viruses
Natural cell process
what is a tumour
Swelling, now commonly a synonym for ’neoplasm’
what is neoplasia
‘new growth’ of abnormal cells
what are the 2 tumour types and which is cancer
Benign- ‘gentle/kind’ - not harmful or non-life threatening
Malignant- ‘evil in nature’ - life threatening- cancer
what is the behavioural classification of neoplasms
benign or malignant
what is the histogenic classification of neoplasms
cell or tissue of origin
growth rate of benign tumours
slow
mitotic figures of benign tumours
rare
histological resemblance to normal tissue of benign tumours
good
do benign tumours invade tissues
no
do benign tumours undergo metastasis
never
what are the borders of a benign tumour like
well defined or encapsulateed
necrosis of benign tumours
rare
the growth rate of malignant tumours
relatively rapid
mitotic figures of malignant tumours
common
malignant tumours’ histological resemblance to normal tissue
variable often poor
do malignant tumours invade tissues
yes
do malignant tumours undergo metastasis
yes
what are the borders of malignant tumours like?
poorly defined or irregular
necrosis of malignant tumours
common
what happens when a benign tumour arises in epithelial or mucosal surfaces?
the tumour grows away from the surface
a polyp will form which is either
pedunculated (stalked)
sessile (sitting on the surface)
this noninvasive outward direction of growth creates anexophyticlesion (grows outwards)
what are the issues with benign tumours?
Pressure on adjacent tissues
Obstruction to the flow of fluid
Production of a hormone
Transformation into a malignant neoplasm
Anxiety
how do malignant tumours form
On epithelial or mucosal surfaces may form a protrusion in early stages, eventually invades the underlying tissue; gives rise to an endophytic tumour (grows inwards).
issues with malignant tumours
Pressure on and destruction of adjacent tissue
Formation of secondary tumours (metastases)
Blood loss from ulcerated surfaces
Obstruction of flow
Production of a hormone
Other paraneoplastic effects cause weight loss and debility
Anxiety and pain.
what are borderline tumours
Show some of the features associated with malignancy but lack the most important criterion of invasion.
Their biological behavior (determined by histology) is intermediate between that of clearly benign and overtly malignant tumours
what is histogenesis
Specific cell or tissue of origin of an individual tumour
what is histology
Microscopic study of biological tissues
Histology is the microscopic counterpart to gross anatomy, and is sometimes referred to as microanatomy
what is histopathology
Microscopic study of diseased tissue
how is the histogenic classification of tumours categorised
epithelial cells (forming carcinomas)
connective tissues or mesenchymal tissues (forming sarcomas)
haematopoietic system (forming leukaemias)
the lymphatic system (forming lymphomas)
what do you call epithelial tumours- benign and malignant
Benign epithelial tumours - papillomas or adenomas*
Malignant epithelial tumours - carcinomas
papilloma= benign tumour of nonglandular or nonsecretory epithelium
adenoma= benign tumour of glandular or secretory epithelium
what do you call mesenchymal tissue tumours- benign and malignant
Benign connective/other mesenchymal tissue tumours - prefix denotes cell of origin
Malignant connective/other mesenchymal tissue tumours – sarcomas
what is tumour grading
Describes how closely the tumour resembles its cell or tissue of origin
what is tissue staging?
Describes the anatomical extent of spread of the tumour
what are the two grading systems of tumours
Numerical: 1/2/3
Description based: Low/medium/high grade or
well/moderately/poorly differentiated
explain the first grade level for tumours
1/low grade/well differentiated: Cells generally resemble the normal cells from which they are derived, are well differentiated, with normal tissue organization, growing slowly – mitotic index low
explain the second level of tumours
2/medium grade/moderately differentiated: Cells may exhibit some loss of differention, cells exhibit abnormalities - abnormal shape, abnormal nuclei, more rapidly growing
explain the third level of tumours
3/high grade/poorly differentiated: Poorly differentiated tissue, abnormal- cell shape, nuclear shape, rapidly growing-mitotic index high
how is tumour staging determined?
Histopathological examination of the tumour
what does the TNM system stand for
Locally T = Tumour
Lymph nodes N = Nodes
Metastasis M = metastasis
what are the genetic causes of cancer
- Mutations, deletions, translocations
- Also Epigenetic changes (e.g. promoter methylation) in cells
what is molecular biology
Studies the composition, structure and interactions of cellular molecules i.e. nucleic acids and proteins
what is carcinogenesis
The process by which normal, healthy cells transform into cancer cells is termed carcinogenesis or oncogenesis
multistep nature of carciogenesis
what are primary cultures used for
test of carciongenic/ oncogenic transformation
how to do a primary culture
The cells from the embryos are enzymatically dissociated.
Seeded as single cells
Treated with radiation or chemicals
Colonies are scored after 8-10 days after staining
normal untransformed embryo cells vs radiation-transformed embryo cells
normal untransformed embryo cells
show contact inhibition
are orderly
Radiation transformed embryo cells
Densely stained
Piled up cells
Random cell arrangement
causes of cancer
Smoking
Diet and lack of exercise
Reproductive life
Viruses
Environmental factors/pollutants
Hormones
Ionising radiation/sunlight
Inherited genes
Translocations
Other acquired gene mutations
Natural cell processes
oncogenes vs tumour suppressor genes
what is the pathways for tumour suppressor and oncogenes
what are proto-goncogenes
normal genes that do not lead to cancer development
what are oncogenes
Proto-oncogenes that have been mutated and lead to cancer development
what kind of protein does proto-oncogene c-sis create
Platelet derived growth factor (PDGF)
Secreted in wound response
what kind of protein does oncogene v-sis create
a truncated version of PDGF protein
Located in the cytoplasm, activates pathway at inappropriate times
what kind of protein does proto-oncogene c-cerB create
epidermal growth factor receptor (EGFR)
what kind of protein does oncogene v-erB create
truncated form of EGFR
Extracellular domain is deleted
what is myc
Myc encodes for a transcription factor protein
Promotes proliferation by controlling the expression of target genes
Including N-Ras and p53
what is K-ras
encodes for a protein expressed in the Ras/MAP kinase pathway
RAS mutations are highly prevalent in lung, colorectal and pancreatic cancers
what is immortalisation
Cell population obtains the ability to multiply indefinitely
how to detect an oncogene in the DNA of cancer cells
cell cycle of oncogenes
what are the epigenetic mechanisms in cancer
Histone acetylation
Histone methylation
DNA methylation
what is DNA methylation
alterations are early events in tumorigenesis
Important in regulation of gene expression in cancer cells
Why is Angiogenesis so important in tumour progression?
Vascular endothelial growth factor (VEGF) is a key growth factor in angiogenesis
VEGFA is secreted from hypoxic cancer cells
This activates VEGF receptor 2 (VEGFR2)
Leads to new blood vessel growth
what is a hallmark
distinguishing characteristic, trait
What are the main hallmarks of cancer
resisting cell death
sustaining proliferative signalling
evading growth suppressors
activation invasion and metastasis
inducing angiogenesis
enabling replicative immortality
what are the emerging hallmarks of cancer
deregulating cellular energetics
avoiding immune destruction
what is angiogenesis
the formation of new blood vessels.
what are the enabling characteristics of cancer
genome instability and mutation
tumour promoting inflammation
what is the detection of cancer
The action or process of identifying the presence of cancer in the absence of signs or symptoms
what is the diagnosis of cancer
The action or process of identifying cancer from its signs and symptoms
how is the diagnosis of cancer done
Taking a clinical history - symptoms
Patient (physical) examination - signs
Perform investigations – imaging,
diagnostic tests on patient samples
what is metastasis
the process whereby malignant tumours spread from their site of origin (theprimary tumour) to form other tumours (secondary tumours) at distant sites
what is the haematogenous route of metastasis
by the blood stream, to form secondary tumours in organs perfused by blood that has drained from a tumour
what is the lymphatic route of metastasis
to form secondary tumours in the regional lymph nodes
what is the transcoelomic route of metastasis
in pleural, pericardial and peritoneal cavities where this invariably results in a neoplastic effusion
what is a prognosis
the anticipated course of the disease in terms of cure, remission, or fate of the patient
how do you predict a cancer prognosis
Type of tumour – classification
Grade of the tumour
Stage of tumour
Patient age and general health – ‘Performance status’
How the tumour is predicted to respond to a treatment
what is adjuvant therapy
treatment given, in the absence of macroscopic evidence of metastases, to patients at risk of recurrence from micrometastases, following treatment given for the primary lesion.
what is neoadjuvant therapy
is given before primary surgery, both to shrink the tumour in order to improve local excision, and to treat any micrometastases as soon as possible.
what is palliative cancer treatment
When cure is no longer possible, palliation – relief of tumour symptoms, preservation of quality of life and prolongation of life is possible in many cancers.
what are the 3 original pillars of cancer treatment
surgery
radiotherapy
chemotherapy
what are additional treatment modalities for solid tumours
Endocrine therapies
Targeted therapies
Immunotherapy
Other treatments: Stem cell transplant, gene therapy, oncolytic viruses
what is a disadvantage of using surgery to treat cancer
If cancer has spread to another part of the body, surgery cannot usually cure it
what is radical radiotherapy
aims to deliver a treatment dose to a well-defined target volume with curative intent, sparing the surrounding normal tissues as much as possible
what is adjuvant radiotherapy
used to reduce the risk of tumour recurrence after primary surgery. The aim of treatment is to eradicate occult (hidden) micrometastatic disease that cannot be demonstrated on imaging.
what is palliative radiotherapy
used to alleviate symptoms of local disease (such as haematuria) or distant metastases (such as bone pain)
what is electromagnetic radiation
X-rays (machine)
Gamma rays (source – radioactive decay)
Particulate radiation
Sub atomic particles including: alpha particles, protons and neutrons
how do you deliver external radiation therapy
Focused beam of radiation dose often delivered in increments (fractionated) separated by at least 4–6 hours, to try and exploit any advantage in DNA repair between normal and malignant cells.
how do you deliver internal radiation therapy
Brachytherapyradiation source placed in close contact with the tissue to provide intense exposure over a short distance to a restricted volume.
how are radiotherapy doses delivered
in fractions
what is the radiotherapy treatment based on
differing biological properties of cancer versus surrounding normal tissues
Regimes amplify survival advantage of normal tissues over cancer cells
Better repair of sub-lethal radiation damage in normal versus cancer cells
Normal cells proliferate more slowly versus cancer cells - therefore have time to repair damage before replication.
what are the types of cancer drugs
Biopharmaceuticals (Biologicals, Biologics)
Living organisms or substances derived from living organisms, or laboratory-produced (recombinant) versions of such substances
Antibody
Virus
Vaccine
how does chemotherapy operate
Operate by interfering with synthesis, structure or function of DNA or mechanics of cell division-often leading to DNA damage
May have narrow therapeutic window due to toxicity towards normal tissue – not cancer specific
what is the chemotherapy treatment strategy
Often given i.v. over period of a few days
Followed by a rest of a few weeks
Normal tissues more proficient at DNA repair than the cancer cells
Deplete the tumour while normal tissues restore between chemotherapy cycle
what are the common side effects of chemotherapy
Nausea and vomiting, hair loss, myelosuppression, mucositis and fatigue
what is patient stratification
The division of a potentialpatientgroup into subgroups, also referred to as ‘strata’ or ‘blocks’
what is personalised medicine of cancer
Treatment based on the molecular profile of a patient’s tumour
what is hormone therapy
drugs that block activity or reduce level of hormone in the body
which cancers are hormone sensitive
breast cancer – tamoxifen
prostate cancer
ovarian cancer
uterine cancer
how does targeted therapy differ from standard chemotherapy
Deliberately designed to act on specific molecules (targets) involved in growth, progression, spread of cancer
Many standard chemotherapies were identified because they just kill proliferating cells by causing DNA damage
Targeted therapies can be small molecules or biopharmaceuticals
what is the most common BRAF mutation
V600E
which mutations do 50% of malignant melanomas have
a point mutation in the BRAF gene
what does V600E mutatuons cause
causes hyperactivation of BRAF kinase to drive malignant melanoma
how does cancer treatment help the immune system fight cancer
Immune system detects and destroys abnormal cells
Immune cells are found in and around tumours
Immune cells are a sign the immune system is responding to the tumour
how is T-cell induced tumour death caused
T- cell receptors can recognize antigens on the tumour
what is PD-L1
PD-L1 interacts with PD-1 on the T cell and suppresses T cell-induced tumour death – immune checkpoint
what is Nivolumab
Targets PD-1, Blocks PD-1/PD-L1 interaction
what is intrinsic cancer drug resistance
Patients show no initial response to a cancer therapy
what is acquired cancer drug resistance
Patients show an initial response to therapy, but subsequently relapse and progress
