Neoplasia Flashcards
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.
Cancer
A swelling; commonly a synonym for ‘neoplasm’
Tumour
A new growth of abnormal cells
Neoplasia
Mitotic figures, or number of dividing cells, in a benign neoplasm is
rare, or low
Histological resemblance to normal tissue in malignant cells is
often poor (poorly differentiated)
The border of a malignant neoplasm is described as
Poorly defined and irregular
The border of a benign neoplasm is described as
well-defined or encapsulated
True or false: Necrosis is common in malignant neoplasms
True
Classification based on the tissue type or cell of origin is known as
histogenetic classification
Malignant neoplasms of epithelial cells are known as
Carcinomas
Malignant neoplasms of connective tissue or mesenchymal tissue are known as
Sarcomas
Malignancies of the haematopoietic system are known as
Leukemias
Malignancies of the lymphatic system are known as
Lymphomas
A benign tumour of non-glandular or non-secretory epithelium is known as a
Papilloma
A benign tumour of glandular or secretory epithelium is known as an
Adenoma
List the three key features assessed in the tumour grading system
- Mitotic activity
- Cellular & nuclear features (size & shape)
- Degree of resemblance to normal tissue (ie differentiation)
A low grade tumour corresponds with what type of cell/tissue differentiation?
Cells are well differentiated (ie closely resemble normal tissue)
Name two qualities of a medium grade tumour
- Cells have some loss of differentiation
- Cells exhibit some abnormalities (abnormal shape, nuclei)
- Growing more rapidly than normal cells
A high grade tumour corresponds with what type of cell/tissue differentiation?
Cells/tissue is poorly differentiated
This is the system commonly used that describes the anatomical extent of spread of the cancer
Tumour staging
What does tumour staging of “N2” signify?
Many lymph nodes involved
What does tumour staging of “M2” signify?
Metastases to multiple organs
What is the numerical range of tumour sizes in the TNM tumour staging system?
1 - 4. Number varies depending on tissue type, rather than by size alone.
According to Duke’s classification system for colorectal cancer stages, a tumour confined to the submucosa is considered grade:
A
According to Duke’s classification system for colorectal cancer stages, a tumour that has spread through the muscularis propria layer, but does not yet involve the lymph nodes is considered grade:
B
According to Duke’s classification system for colorectal cancer stages, a tumour that has spread to at least one lymph node is considered grade:
C
According to Duke’s classification system for colorectal cancer stages, a tumour that has spread to another part of the body is considered grade:
D
What types of changes to DNA can cause cancer (3)
Mutations, deletions, translocations
Changes in organisms caused by modification of gene expression
Epigenetics
Promoter methylation is an example of
an epigenetic change
A mutation in this type of gene results in a gain of function, where the protein product is produced in higher quantities
Oncogene
Oncogenes need a mutation in how many alleles in order to result in abnormal cell growth?
One
A mutation in this type of gene causes a loss of function
Tumour suppressor gene
Tumour suppressor genes need a mutation in how many alleles to result in abnormal cell growth?
Generally two (recessive), though haploinsufficiency can occur in some cases of one mutated allele
Abnormal cell growth resulting from one mutated allele in a tumour suppressor gene is known as
Haploinsufficiency
Name two examples of oncogenes
K-Ras (or H-Ras, N-Ras), or Myc
K-Ras encodes for a protein expressed in the Ras/MAP __________ pathway.
kinase
What type of mutation is prevalent in lung, colorectal, and pancreatic cancers?
K-Ras (oncogene) mutation
Physiologic regulators of cell proliferation and differentiation are known as
Proto-oncogenes
These types of genes are characterised by the ability to promote cell growth in the absence of normal mitogenic signals
Oncogenes
This type of oncogene encodes for a transcription factor protein, and promotes proliferation by controlling the expression of target genes, including N-Ras and p53. This leads to processes like immortalisation, proliferation, and apoptosis.
Myc
List some examples of tumour suppressor genes
- BRCA 1 & BRCA 2
- TP53, which codes for p53
- Rb1
Rb1 is associated with what type of cancer?
Retinoblastoma
Name the six hallmark features of cancer: (remember I’m PEARR)
- Proliferative signalling
- Evading growth suppressors
- Invasion & metastases
- Replicative immortality
- Angiogenesis
- Resisting cell death
Cancer cells don’t rely on external signals in order to divide. They have acquired a number of mutations that short circuit growth factor pathways, leading to unregulated growth. This describes which hallmark feature of cancer?
- Sustaining proliferative signalling
Cancer cells don’t respond to growth inhibitory signals becuase of mutations they’ve obtained, or gene silencing (epigenetics). This describes which hallmark of cancer?
- Evading growth suppressors
When cancer cells spread around the body and cause malignant disease, invading organs and compromises the function of the body. This corresponds with which hallmark of cancer?
- Activating invasion and metastasis
Unlimited replicative potential due to long telomeres corresponds with which hallmark of cancer?
- Enabling replicative immortality
Cancer cells form new blood vessels that the tumour relies on for survival and expansion. This corresponds with which hallmark of cancer?
- Inducing angiogenesis
Cancer cells can evade apoptotic signals. This corresponds with which hallmark of cancer?
- Resisting cell death
Name the two emerging hallmarks of cancer
- Deregulating cellular energetics
8. Avoiding immune desctruction
Cancer cells demand an increase of fuel via synthetic prescursors. This corresponds with which emerging hallmark of cancer?
- Deregulating cellular energetics
Cancer cells interfere with the body’s immune response to avoid destruction. This corresponds with which emerging hallmark of cancer?
- Avoiding immune destruction
List the two enabling characteristics that go along with the hallmarks of cancer
- Tumour promoting inflammation
2. Genome instability and mutation
What is “the key to all of the other hallmarks (of cancer), and to cancer taking hold?
Genome instability and mutation
Inflammatory cells provide _________ and _________ that promote angiogenesis and invasion
growth factors and enzymes
What type of drugs act on the pathway of cancer cells sustaining proliferative signalling?
- EGFR inhibitors
What type of drugs act on the pathway of cancer cells enabling replicative immortality?
- Telomerase inhibitors
What type of drugs act on the pathway of cancer cells inducing angiogenesis?
- Inhibitors of VEGF signaling
Tumours can either be classified based on their ________ or by their __________
behaviour (benign or malignant, grade/stage), or by their histogenic classification
Histogenetic classification refers to the
cell or tissue of origin
What two things determine whether treatment will be curative or palliative?
Diagnosis and prognosis
The anticipated course of the disease in terms of cure, remission, or fate of the patient
Prognosis
What types of interventions can influence a cancer prognosis? (2)
Medical or surgical interventions
Name 5 things that determine the cancer prognosis for a patient
- Tumour classification
- Grade
- Stage
- Age and general health of pt
- How the tumour is predicted to respond to a tx
Treatment given, in the absence of macroscopic evidence of metastasis, to patients at risk of recurrence from micrometasteses, following treatment given for the primary lesion. This describes what type of treatment therapy?
Adjuvant
Treatment 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. This describes what type of therapy?
Neo-adjuvant
Priorities of this type of treatment provide relief of tumour symptoms, preservation of quality of life, and prolongation of life
Palliative
Name the original “Three pillars of cancer treatment”
- Surgery
- Radiotherapy
- Chemotherapy
Name the three additional types of systemic drug therapies (other than chemotherapy)
Endocrine therapies
Targeted therapies
Immunotherapy
What is one benefit of robot-assisted keyhole surgery?
Less invasive that traditional surgical techniques
True or false: surgical resection of a tumour can be curative as long as the cancer is contained in that one area and hasn’t spread.
True
This type of radiotherapy aims to deliver a treatment dose to a well-defined target volume with curative intent.
Radical radiotherapy
This type of radiotherapy is 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.
Adjuvant radiotherapy
This type of radiotherapy is used to alleiviate symptoms of local disease (such as haematuria) or distant metastases (such as bone pain.
Palliative radiotherapy
What are the three types of external radiotherapy?
- Fractionated external beam
- Stereostatic radiotherapy/radiosurgery
- Proton beam therapy
This type of radiotherapy delivers radiation doses in increments separated by at least 4-6 hours. It aims to exploit any advantage in DNA repair between normal and malignant cells.
Fractionated external beam
This type of radiotherapy can concentrate XRays or gamma radiation from multiple sources onto a small volume
Stereostatic radiosurgery/ radiotherapy
This type of radiotherapy uses charged proton particules with little side scatter, has a focused beam, and provides less of a dose to the surrounding tissue
Proton beam therapy
Which of the external types of radiotherapies are recommended for use in children?
Proton beam therapy
Name the two types of internal radiotherapy
Bracytherapy and systemic radionuclides
This type of radiotherapy uses a radiation source that is placed in close contact with the tissue to provide intense exposure over a short distance to a restricted volume
Brachytherapy
This type of radiotherapy is delivered intravenously or as a drink
Systemic radionuclides
Systemic radionuclides such as 131-iodine are used in the treatment of what type of cancer?
Thyroid cancer
Which type of cells exhibit better repair after sub-lethal doses or radiation damage- cancer cells or normal cells?
Normal cells
Which cell type proliferates more rapidly- cancer cells or normal cells?
Cancer cells
Explain the basis of giving radiotherapy in incremental doses
Normal cells proliferate more slowly than cancer cells, therefore they have more time to repair damage before replication.
List the common side effects with chemotherapy
- Nausea & vomiting
- Hair loss
- Myelosuppression
- Mucositis
- Fatigue
Name two examples of cytotoxic chemotherapy drugs
Cisplatin and Paclitaxel
“Small molecule” cancer drugs include:
- Cytotoxic chemotherapy drugs
- Targeted therapies
- Immunotherapies
The “biologic” cancer drugs include:
- Antibodies (targeted therapies and immunotherapy)
- Oncolytic viruses
- Vaccines (immunotherapy)
These types of cancer drugs interfere with specific molecular targets involved in growth, progression, and spread of cancer. Can be small molecule drugs OR biologics.
Targeted therapies
Name an example of a small molecule targeted therapy drug
Vemurafenib (Zelboraf)
The mechanism of action for this drug is to block activity of V600E BRAF
Vemurafenib (Zelboraf)
What type of cancer does Vemurafenib (Zelboraf) treat?
Malignant melanoma
What is the effect of blocking V600E BRAF?
Decrease in excess melanocyte proliferation
Name two examples of drugs that are antibodies (discussed in lecture)
Trastuzumab (Herceptin) and Nivolumab (Opdivo)
This drug binds to and blocks the HER2 protein receptor, affecting the signalling of tyrosine kinase
Trastuzumab (Herceptin)
This drug blocks PD1/PDL-1 interaction, which relieves the suppression of T cell activity. An immune checkpoint inhibitor
Nivolumab (Opdivo)
What type of cancer is Nivolumab (Opdivo) used to treat?
Malignant melanoma
What type of cancer is Trastuzumab (Herceptin) used to treat?
Breast cancer
What is the effect of PD1/PDL-1 interaction in a cancer cell?
Leads to suppression of T cell activity
This type of therapy treats cancers that are hormone sensitive
Endocrine therapies
Which endocrine therapy is used in the treatment of breast cancer?
Tamoxifen
What is the mechanism of action for Tamoxifen?
Blocks estrogen receptors
What type of drugs are endocrine drugs? Small molecule or biologics?
Small molecule
Which types of cancers are hormone sensitive?
Breast, ovarian, womb, and prostate
Examples of immunotherapy type cancer drugs include:
Vaccines
Immune system modulators
Checkpoint inhibitor therapies
Cancer drug resistance can be either __________ or _________.
Intrinsic or acquired
In this type of drug resistance, treatment naive patients show no response to a cancer therapy.
Intrinsic
In this type of drug resistance, patients show initial response to therapy, but subsequently relapse and progress
Acquired
What are the mechanisms of cancer drug resistance?
- Altered ________ transport
- Enhanced ___ repair
- __________ pathway defects
- Alteration of _________ molecules
- Altered membrane transport
- Enhanced DNA repair
- Apoptotic pathway defects
- Alteration of target molecules
What is the biomarker associated with malignant melanoma (immune checkpoint that suppresses T cell tumour death activity?)
PD-L1