Biology of Cancer Flashcards
What is Cancer
- CDC defines cancer as “____ ___ and ___ of ____ cells in the body”
- Not all tumors are cancer!
- Tumors can be benign or malignant
- Benign
- Benign tumors are___ ____
- Cells from benign tumors ____ _____ but do not ____ to other parts of the body.
- They usually can be ____ and, in most cases, they ___ ___ ___ ___
- Malignant
- Malignant tumors are ___
- Cells from malignant tumors can___ and ___ tissues ___ the tumor, and they can____ to other parts of the body (metastasize).
- There are two types of malignant tumors:
- 1._____
- _____ in origin.
- Most _____ type of cancer.
- Common sites of carcinomas are the ___ ___ ___ ___ ___ __ ___
- 2._____
- Cancers of ____ and ____ tissue (ie., ____ in origin).
- Sarcomas can be found _____in the body, and they often form ____ ____ in the____.
*
- 1._____
- Benign
- Tumors can be benign or malignant
What is Cancer
CDC defines cancer as “uncontrolled growth and spread of abnormal cells in the body”
Not all tumors are cancer!
Tumors can be benign or malignant
Benign
Benign tumors are not cancer.
Cells from benign tumors proliferate uncontrollably but do not spread to other parts of the body.
They usually can be removed and, in most cases, they do not come back.
Malignant
Malignant tumors are cancer.
Cells from malignant tumors can invade and damage tissues near the tumor, and they can spread to other parts of the body (metastasize).
There are two types of malignant tumors:
1.Carcinomas
Epithelial in origin.
Most common type of cancer.
Common sites of carcinomas are the skin, mouth, lung, breast, stomach, colon and uterus.
2.Sarcomas
Cancers of connective and supportive tissue (ie., mesenchymal in origin).
Sarcomas can be found anywhere in the body, and they often form secondary growths in the lungs.
Cancer of the oral cavity and pharynx
Incidence rates are more than twice as high in ___ as in ____
Recent studies have shown that incidence is increasing for cancers of the oropharynx that are associated with ____________ infection among white men and women.
Cancer of the oral cavity and pharynx
Incidence rates are more than twice as high in men as in women.
Recent studies have shown that incidence is increasing for cancers of the oropharynx that are associated with human papillomavirus (HPV) infection among white men and women.
Cancers are highly complex
Cancer cells have defects in regulatory circuits that govern normal ___ ____ and ____.
There are more than ____distinct types of cancer and ____ of tumors can be found within specific ____ – highly complex.
Complexity of cancer provokes an important question - How many distinct regulatory circuits within each type of target cell must be disrupted in order for such a cell to become cancerous?
Cancers are highly complex
Cancer cells have defects in regulatory circuits that govern normal cell proliferation and homeostasis.
There are more than 100 distinct types of cancer and subtypes of tumors can be found within specific organs – highly complex.
Complexity of cancer provokes an important question - How many distinct regulatory circuits within each type of target cell must be disrupted in order for such a cell to become cancerous?
Cancer arises from the accumulation of ____ genetic changes in the same cell
Mutation of a single gene (proto-oncogene/tumor suppressor) causes____ ___cancer but does not cause cancer
Need 4 or more mutations to become cancerous
Cancer arises from the accumulation of several genetic changes in the same cell
Mutation of a single gene (proto-oncogene/tumor suppressor) causes predisposition to cancer but does not cause cancer
Need 4 or more mutations to become cancerous
Ex - Multi-step carcinogenesis in colon cancer
Adenoma –____tumor. It starts in ____-____ cells of the _____ tissue
Carcinoma - An invasive malignant tumor derived from epithelial tissue that tends to metastasize to other areas of the body
Ex - Multi-step carcinogenesis in colon cancer
Adenoma – Benign tumor. It starts in gland-like cells of the epithelial tissue
Carcinoma - An invasive malignant tumor derived from epithelial tissue that tends to metastasize to other areas of the body
Hallmarks of cancer 2000
Cancer cells are characterized by certain key properties:
___ ____ in ___ signals
____ to ____ ____ (____) signals
____ of ____
____ ____ ____
____ ______– increased supply of ____. Ability to form _____
____ ____ and ____ - It is this property that is generally responsible for the deaths of patients who have cancer.
Hallmarks of cancer 2000
Cancer cells are characterized by certain key properties:
Self-sufficiency in growth signals
Insensitivity to growth-inhibitory (antigrowth) signals
Evasion of apoptosis
Limitless replicative potential
Sustained angiogenesis – increased supply of nutrients. Ability to form vasculature
Tissue invasion and metastasis - It is this property that is generally responsible for the deaths of patients who have cancer.
Self-Sufficiency in Growth Signals
Normal cells depend on _____ growth signals to _____ (___ or ____ stimulation).
- Paracrine or endocrineà Have to come from another nearby cell or elsewhere in the body
These signals are transmitted into the cell by ______ receptors that bind distinctive classes of _____ molecules.
Cancer cells show reduced _____ on exogenous growth stimulation and they achieve this through different mechanisms.
- Cancer cells produce___ ___ ____themselves, to which they can ____ via the expression of ____ receptors, resulting in _____ proliferative stimulation.
- Cancer cells express___ ____ ____ ____ ____ _____ and/or___ ____(Ras, Raf).
- Growth Factor Receptor or the Downstream Signaling Molecules are made constitutively, independent of extracellular cue
- Cancer cells over express ___ ____ _____ and become _____ to growth signals.
- Disruptions of ____ _____ mechanisms that_____ proliferative signaling.
- Since signals cross talk and form circuits, cancer cell _____ the circuit for their benefit.
- Newer theory – cancer cells send ____ to stimulate ____ cells within the supporting tumor-associated environment, which reciprocate by _____ the cancer cells with various ___ ____
Cancer cells induce their neighbors to release abundant fluxes of ___ _____ signals
- Old school thought: The _____ View
- Focuses only on the properties of the ____ cells.
- Newer Thought: A ____ ____ ____
- Considers the _____ of the cancer and how___ ____ that are in that environment are ___ by cancer cells to support_____ of cancer cells
*
- Considers the _____ of the cancer and how___ ____ that are in that environment are ___ by cancer cells to support_____ of cancer cells
Self-Sufficiency in Growth Signals
Normal cells depend on exogenous growth signals to proliferate (paracrine or endocrine stimulation).
Paracrine or endocrineà Have to come from another nearby cell or elsewhere in the body
These signals are transmitted into the cell by transmembrane receptors that bind distinctive classes of signaling molecules.
Cancer cells show reduced dependence on exogenous growth stimulation and they achieve this through different mechanisms.
Cancer cells produce growth factor ligands themselves, to which they can respond via the expression of cognate receptors, resulting in autocrine proliferative stimulation.
Cancer cells express constitutively active mutant growth factor receptors (EGFR) and/or signaling proteins (Ras, Raf).
Growth Factor Receptor or the Downstream Signaling Molecules are made constitutively, independent of extracellular cue
Cancer cells over express growth factor receptors and become hypersensitive to growth signals.
Disruptions of negative-feedback mechanisms that attenuate proliferative signaling.
Since signals cross talk and form circuits, cancer cell reprogram the circuit for their benefit.
Newer theory – cancer cells send signals to stimulate normal cells within the supporting tumor-associated environment, which reciprocate by supplying the cancer cells with various growth factors.
Cancer cells induce their neighbors to release abundant fluxes of growth-stimulating signals
Old school thought: The Reductionist View
Focuses only on the properties of the cancer cells.
Newer Thought: A heterotypic Cell Biology
Considers the microenvironment of the cancer and how other cells that are in that environment are tricked by cancer cells to support growth of cancer cells
Insensitivity to growth-inhibitory signals
In normal cells multiple ______ signals operate to maintain cellular _____.
These signals, depending on the environment, induce the cells to enter ___ phase or to permanently ____ their proliferative potential by being induced to ____
Cancer cells ____ the antiproliferative signals – typically due to mutations in ___ ____.
Ex –
In cancer cells, disruption or loss of the ______ protein in the G1 checkpoint, which normally determines if the cell should progress through the cell cycle or not, ____ E2Fs and thus allows cell proliferation, rendering cells ____ to antigrowth factors that normally operate along this pathway to block advance through the __ phase of the cell cycle.
Similarly, loss of ____ renders insensitivity to growth-inhibitory signals
Insensitivity to growth-inhibitory signals
In normal cells multiple antiproliferative signals operate to maintain cellular quiescence.
These signals, depending on the environment, induce the cells to enter G0 phase or to permanently relinquish their proliferative potential by being induced to differentiate.
Cancer cells evade the antiproliferative signals – typically due to mutations in tumor suppressors.
Ex –
In cancer cells, disruption or loss of the retinoblastoma (Rb) protein in the G1 checkpoint, which normally determines if the cell should progress through the cell cycle or not, liberates E2Fs and thus allows cell proliferation, rendering cells insensitive to antigrowth factors that normally operate along this pathway to block advance through the G1 phase of the cell cycle.
Similarly, loss of p53 renders insensitivity to growth-inhibitory signals
Evasion of apoptosis
In normal cells, programmed cell death by apoptosis serves as a ___ ____ to cancer development.
Cancer cells evade apoptosis by several mechanisms
- Most common is the ___ ___ ______ _____ _____function, which eliminates this critical ___ ____ from the apoptosis-inducing circuitry.
- Cancer cells express high levels of _______ regulators or ____ signals.
- Cancer cells express low levels of ____ factors.
- Cancer cells short-circuit the ____ ____ _____death pathway.
Evasion of apoptosis
In normal cells, programmed cell death by apoptosis serves as a natural barrier to cancer development.
Cancer cells evade apoptosis by several mechanisms
Most common is the loss of p53 tumor suppressor function, which eliminates this critical damage sensor from the apoptosis-inducing circuitry.
Cancer cells express high levels of anti-apoptotic regulators or survival signals.
Cancer cells express low levels of pro-apoptotic factors.
Cancer cells short-circuit the extrinsic ligand-induced death pathway.
Limitless replicative potential
Normal cells pass through only a ___ number of successive cell growth-and-division cycles.
___ ____ is a clocking mechanism that determines the limited replicative potential of normal cell- the length of telomeric DNA in a cell dictates how many successive cell generations its progeny can pass through before telomeres are largely eroded and have consequently lost their ____ functions, triggering___ ____
Cancer cells express high levels of ____ (which is absent in normal ____ ____cells), a specialized ___ polymerase, that adds ____ ____ segments to the ends of telomeric DNA.
Note - Normal human tissues shown to be telomerase-positive are
____ ____
____ ____
____ ____
____ ____ _____
____ ____
____ _____
Limitless replicative potential
Normal cells pass through only a limited number of successive cell growth-and-division cycles.
Telomere shortening is a clocking mechanism that determines the limited replicative potential of normal cell- the length of telomeric DNA in a cell dictates how many successive cell generations its progeny can pass through before telomeres are largely eroded and have consequently lost their protective functions, triggering cell death.
Cancer cells express high levels of telomerase (which is absent in normal differentiated somatic cells), a specialized DNA polymerase, that adds telomere repeat segments to the ends of telomeric DNA.
Note - Normal human tissues shown to be telomerase-positive are intestinal epithelium, esophageal epithelium, cycling endometrium, basal keratinocytes, cervical epithelium, and hematopoietic stem cells.
Sustained angiogenesis
Like normal tissues, tumors require sustenance in the form of___ and ____ as well as an ability to ____metabolic wastes and____ ____
Development of ____ is active during ____ but is quiescent in ____ (except in ___ ____ and ___ ____ ___ when angiogenesis is ____ turned on).
However, during tumor progression, an “angiogenic switch” is almost always ____and remains __, causing normally quiescent vasculature to continually sprout ___ ___that help ___ expanding ___ growths.
Angiogenic switch in tumors occurs due to increased ____ through ___ ____ ___ ___
Sustained angiogenesis
Like normal tissues, tumors require sustenance in the form of nutrients and oxygen as well as an ability to evacuate metabolic wastes and carbon dioxide.
Development of vasculature is active during embryogenesis but is quiescent in adults (except in wound healing and female reproductive cycling when angiogenesis is transiently turned on).
However, during tumor progression, an “angiogenic switch” is almost always activated and remains on, causing normally quiescent vasculature to continually sprout new vessels that help sustain expanding neoplastic growths.
Angiogenic switch in tumors occurs due to increased signaling through vascular endothelial growth factor (VEGF).
Steps in tissue invasion and metastasis
There are several steps in tissue invasion and metastasis of cancer cells:
First need to get a ___ that lets them metastasize
Begins with___ ____
____ by cancer cells into nearby ___ and____ vessels (Enter the blood stream)
____of cancer cells through the ____ and ___ systems
____ of cancer cells from the ____ of such vessels into the ____ of distant tissues (_____)
The formation of small ___ of cancer cells (____)
Growth of _____ lesions into _____ tumors
Steps in tissue invasion and metastasis
There are several steps in tissue invasion and metastasis of cancer cells:
First need to get a mutation that lets them metastasize
Begins with local invasion
Intravasation by cancer cells into nearby blood and lymphatic vessels (Enter the blood stream)
Transit of cancer cells through the lymphatic and hematogenous systems
Escape of cancer cells from the lumina of such vessels into the parenchyma of distant tissues (extravasation)
The formation of small nodules of cancer cells (micrometastases)
Growth of micrometastatic lesions into macroscopic tumors
Hallmarks and Causes
__________:Low levels of pro-apoptotic factors, Mutations in tumor suppressors
______________: Autocrine Proliferative Stimulation
_________________: Increased signaling thru vascular endothelial growth factor
________________: Mutations in tumor suppressors,
_______________: Expression of high levels of telomerase
Hallmarks and Causes
Evasion of Apoptosisà Low levels of pro-apoptotic factors, Mutations in tumor suppressors
Self Sufficiency in Growth Signalsà Autocrine Proliferative Stimulation
Sustained Angiogenesisà Increased signaling thru vascular endothelial growth factor
Insensitivity to growth inhibitory signalsà Mutations in tumor suppressors,
Limitless replicative potentialà Expression of high levels of telomerase
Parallel pathways of tumorigenesis
The 6 hallmarks of cancer can be acquired by a cell in different _____ and ____ to become tumorigenic
Need ___ of these hallmarks but not __ to become cancerous
Parallel pathways of tumorigenesis
The 6 hallmarks of cancer can be acquired by a cell in different combinations and orders to become tumorigenic
Need most of these hallmarks but not all to become cancerous
Emerging hallmarks of cancer 2011
Recent research suggests that there are more than the basic 6 hallmarks of cancer. A few are:
____ ____ ____ – ie., ability to reprogram cellular ____ in order to support the increased proliferation.
Avoiding ___ ____ – ability to evade immunological destruction by _ and _ lymphocytes.
___ _____ – acquired ability to ____ their genetic material to drive tumor progression.
___ ___ ____ – Inflammation by ___ immune cells designed to ___ ____ and ___ ___s instead start ____ tumor growth.
Emerging hallmarks of cancer 2011
Recent research suggests that there are more than the basic 6 hallmarks of cancer. A few are:
Deregulating cellular energetics – ie., ability to reprogram cellular metabolism in order to support the increased proliferation.
Avoiding immune destruction – ability to evade immunological destruction by T and B lymphocytes.
Genomic instability – acquired ability to mutate their genetic material to drive tumor progression.
Tumor-promoting inflammation – Inflammation by innate immune cells designed to fight infections and heal wounds instead start promoting tumor growth.
