Lecture 1 – Hallmarks of cancer.
Cancer is a set of diseases that is characterised by unregulated cell growth, leading to the
invasion of surrounding tissues and spreads to other parts of the body. It’s a disease which
involves dynamic changes in the genome.
There are over 200 different types of cancers and they can affect multiple tissues.
They can be classified into different types of tumours. The 2 main types are
solid tumours
blood cell cancers.
solid tumours generally originate from epithelial cells, they can develop into cancer cells. They
are exposed to a range of carcinogens, e.g. tobacco smoke in the lung. This can cause them to
acquire mutations.
Blood cell cancers leukaemia and lymphoma, they are a disease of haematopoietic stem
cells
Hanaghan and Weinberg 2000.
- Proposed that six hallmarks of cancer together constitute an organising principle that
provides a logical framework for understanding the remarkable diversity of neoplastic
diseases.
- As normal cells evolve progressively to a neoplastic state (cancer state) they acquire a
succession of these hallmark capabilities (they acquire mutations)
- The multistep process of human tumour pathogenesis could be rationalized by the need of
incipient cancer cells to acquire the traits that enable them to become tumorigenic and
ultimately malignant: which is proliferating in an uncontrolled fashion.
Hallmarks of normality:
The default position for all cells is quiescence, as the tissue grows, they sense that they are in
contact with their neighbours and stop proliferating. It’s a state of dormancy. This process can
be regulated (turned off and on).
all mammalian cells contain the same regulatory mechanisms controlling
-differentiation
-proliferation
-death
Hallmarks of normal cells are
1) They respond to growth factors leading to proliferation
2) They respond to antigrowth factors, preventing proliferation or inducing terminal
, differentiation
3) They require signals to prevent death by apoptosis
4) They require a supply of nutrients for survival e.g. oxygen and glucose
5) Restricted replication potential.
-Growth factors. All growth factors stimulate the MAP kinase pathway, kinases can be
mutated/ dysregulated e.g. RAF and RAS.
-Antigrowth factors. Normal cells express antigrowth factors
-Apoptosis. Cells can become damaged by UV light/ chemicals etc, and they can be killed by a
controlled cell death.
- Only 10% of cancers are due to an inherited defect, 90% of them are due to somatic
mutations in individual cells.
- The conversion of a normal cell to a cancer cell requires 4-7 stochastic/ random events, this
is a multi-step process that ranges from SNP to whole chromosome disruption.
- There are 6 acquired abilities to all cancers which are known as the hallmarks of cancers.
1) sustained proliferative signalling
(self-sufficiency in growth signals-
don’t need the external cues) EGFR
inhibitors.
2) evading growth suppressors
(insensitive to growth inhibitory
signals) cyclin dependent kinase
inhibitors.
3) resisting cell death (evasion of
programmed cell death) pro
apoptotic BH3 mimetics.
4) enabling replicative immortality
(they have limitless replicative
potential) telomerase inhibitors
5) sustained angiogenesis (turn on
blood supply to the tumours to give
nutrients for growth) inhibitors of VEGF signalling
6) tissue invasion and metastasis (breaks away from the primary site and spreads to the
body) inhibitors of HGF/ c-MET
These hallmarks have to be acquired to allow the cancer cells to spread and kill the patient.
1) Sustained proliferative signalling.
Normal cells require mitogenic growth signals before they can change from the quiescent state to
the active proliferative state.
No normal cell can divide without external signals which may be
- diffusible growth factors
- extracellular matrix components
- cell-cell adhesion molecules
The requirement of external signals is shown when normal cells are cultures, which only proliferate
Cancer is a set of diseases that is characterised by unregulated cell growth, leading to the
invasion of surrounding tissues and spreads to other parts of the body. It’s a disease which
involves dynamic changes in the genome.
There are over 200 different types of cancers and they can affect multiple tissues.
They can be classified into different types of tumours. The 2 main types are
solid tumours
blood cell cancers.
solid tumours generally originate from epithelial cells, they can develop into cancer cells. They
are exposed to a range of carcinogens, e.g. tobacco smoke in the lung. This can cause them to
acquire mutations.
Blood cell cancers leukaemia and lymphoma, they are a disease of haematopoietic stem
cells
Hanaghan and Weinberg 2000.
- Proposed that six hallmarks of cancer together constitute an organising principle that
provides a logical framework for understanding the remarkable diversity of neoplastic
diseases.
- As normal cells evolve progressively to a neoplastic state (cancer state) they acquire a
succession of these hallmark capabilities (they acquire mutations)
- The multistep process of human tumour pathogenesis could be rationalized by the need of
incipient cancer cells to acquire the traits that enable them to become tumorigenic and
ultimately malignant: which is proliferating in an uncontrolled fashion.
Hallmarks of normality:
The default position for all cells is quiescence, as the tissue grows, they sense that they are in
contact with their neighbours and stop proliferating. It’s a state of dormancy. This process can
be regulated (turned off and on).
all mammalian cells contain the same regulatory mechanisms controlling
-differentiation
-proliferation
-death
Hallmarks of normal cells are
1) They respond to growth factors leading to proliferation
2) They respond to antigrowth factors, preventing proliferation or inducing terminal
, differentiation
3) They require signals to prevent death by apoptosis
4) They require a supply of nutrients for survival e.g. oxygen and glucose
5) Restricted replication potential.
-Growth factors. All growth factors stimulate the MAP kinase pathway, kinases can be
mutated/ dysregulated e.g. RAF and RAS.
-Antigrowth factors. Normal cells express antigrowth factors
-Apoptosis. Cells can become damaged by UV light/ chemicals etc, and they can be killed by a
controlled cell death.
- Only 10% of cancers are due to an inherited defect, 90% of them are due to somatic
mutations in individual cells.
- The conversion of a normal cell to a cancer cell requires 4-7 stochastic/ random events, this
is a multi-step process that ranges from SNP to whole chromosome disruption.
- There are 6 acquired abilities to all cancers which are known as the hallmarks of cancers.
1) sustained proliferative signalling
(self-sufficiency in growth signals-
don’t need the external cues) EGFR
inhibitors.
2) evading growth suppressors
(insensitive to growth inhibitory
signals) cyclin dependent kinase
inhibitors.
3) resisting cell death (evasion of
programmed cell death) pro
apoptotic BH3 mimetics.
4) enabling replicative immortality
(they have limitless replicative
potential) telomerase inhibitors
5) sustained angiogenesis (turn on
blood supply to the tumours to give
nutrients for growth) inhibitors of VEGF signalling
6) tissue invasion and metastasis (breaks away from the primary site and spreads to the
body) inhibitors of HGF/ c-MET
These hallmarks have to be acquired to allow the cancer cells to spread and kill the patient.
1) Sustained proliferative signalling.
Normal cells require mitogenic growth signals before they can change from the quiescent state to
the active proliferative state.
No normal cell can divide without external signals which may be
- diffusible growth factors
- extracellular matrix components
- cell-cell adhesion molecules
The requirement of external signals is shown when normal cells are cultures, which only proliferate
