Cancer Flashcards
Cancer classification
depends on :
* the site of origin
* Stage (T1-T4, N0-N1, M0-M1)
T4, N1, M1 need systemic treatment
Tumor grading ((differentiation), G1-G3)
Cancer origin
Carcinogen – a cancer-inducing agent
Genetic changes that cause cancer:
- errors that occur as cells divide.
- damage to DNA caused by harmful substances in the environment, such as the chemicals in
tobacco smoke and ultraviolet rays from the sun
- they were inherited from our parents.
- Viruses
Examples
- Soot –suggested to be the cause of scrotum cancer in chimney sweeps
- Benzene – a colourless liquid, that rapidly evaporates (carcinogenic,
causes leukemia); - Asbestos - a group of six different naturally occurring fibrous minerals
that can be separated into long fibers (lung cancer) - Radon - a colorless and odorless radioactive gas (lung cancer)
1895 – exposure to x-rays can include tissues damage and lead to the
development of cancer
1910 – submicroscopic agent isolated from a chicken tumor can induce new
tumors in healthy chickens (Roussarcoma virus)
1927 – Herman Muller notice that X-ray of fruit flies resulted in mutant offspring
Microbial Mechanisms can aid both Oncogenesis and Tumor Suppression
Cancer drivers
mutations in
proto-oncogenes, tumor suppressor genes, and DNA repair genes
Mechanism of proto-oncogene activation to oncogene in cancer:
1. translocation
2. gene amplification
3. point mutation within control element
result in more protein
4.point muttion within gene
may result in more active or degradation resistant protein
Hallmarks of cancer
Original Hallmarks:
1.sustained proliferative signaling
2.Evading growth suppressors
3.Enabling replicative imortality
4. Activationg invasion and metastasis
5. inducing angiogenesis
6. Resisting cell death
Emerging hallmarks :
1.Avoiding immune distraction
2.Deregulating cellular energetics
Enabling factors
1. Genome instability and mutation
2. Tumor promoting inflamation
Other factors:
1. Polymorphic microbioms
2. Senescent cells
3. Unlocking phenotypic plasticity
4. Non mutational epigenetic programing
Signalling pathways in cancer
- Cell cycle
- P53 pathway (tumor suppressor pathway)
- Myc ( MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis)
- PI3K pathway (cancer cell growth)
- Hippo pathway On-inhibits growth , proliferation , OFF- allows growth and proliferation )
- Notch pathway (hyperactivation has been implicated as oncogenic in several cancers)
- Keap-Nrf2 pathway ( in oxidative stress conditions - production of antioxidants
- Wnt pathway (cell fate determination)
- Tgf-beta pathway (before tumor creation antiproliferative effects -after tumor creation angiogenesis, immunosupression , tumor growth )
Cancer therapy
Biomarker Testing
* Chemotherapy
* Hormone Therapy( Tamoxifen estrogen antagonist stops proliferation )
* Hyperthermia
* Immunotherapy ( special T-cells or Immune checkpoint inhibitors)
* Photodynamic Therapy (To activate a chemical – known as a photosensitizing agent – that kills only the cancer
cells.
- Radiation Therapy
- Stem Cell Transplant (Once they enter your bloodstream, the stem cells travel to the bone marrow, where they take the place of the cells that were destroyed by treatment)
- Surgery
- Targeted Therapy ( type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread. It is the foundation of precision medicine.)
Types of Cancer?
Carcinoma – formed by epithelial cells
Adenocarcinoma
Basal cell carcinoma
Squamous cell carcinoma
Transitional cell carcinoma
Sarcoma – formed in in bone and soft tissues,
Lymphoma – begins in lymphocytes
Multiple myeloma – begins in plasma cells
Melanoma – begins in cells that become melanocytes
Brain and Spinal Cord Tumors
Neuroendocrine Tumors – begins from cells that release hormones
Carcinoid Tumors – type of endocrine tumor
What distinguish normal and cancer cells?
Most of cancer cells are
* insensitive to density-dependent inhibition of cell proliferation
* have reduced requirements for extracellular growth factors
* autocrine growth stimulation
* No contact inhibition
* secrete proteases that digest extracellular matrix components
* secrete growth factors that promote the formation of new blood vessels
(angiogenesis)
* Fail to differentiate normally
* failure to undergo programmed cell death contribute to tumor development
The stages of tumor development?
cell with genetic mutation- hyperplasia-dysplasia- in situ cancer- invasive cancer
Cell biologists studied the characteristics of cancer cells and found:
Cancer cells – abnormal cells that arise from the body’s normal tissues
All cells in the tumor must have descended from a single ancestral cell
The development of cancer – a result of series of clonal expansions from a single
ancestral cell.
A series of changes leads to tumor formation.
Cancer cells are genetically unstable
How cancer diagnosed?
Imaging tests used in cancer
CT scan
MRI
Nuclear scan
Bone scan
PET scan
Ultrasound
X-rays
Biopsy:
with a needle
with endoscopy
with surgery
Lab tests:
Blood chemistry test
Complete blood count (CBC)
Cytogenetic analysis
Immunophenotyping
Liquid biopsy
Sputum cytology
Tumor marker tests
Urinalysis
Urine cytology
Cancer prevention?
- Vaccine
- prophylaxis against HBV infection prevents HCC
- Anti-ER ( estrogen receptor ) to prevent breast cancer
- COX2 inhibitors, aspirin (colorectal cancer)
- Selenium, vitamin D (no clear evidence: melanoma, lung cancer)
- triple therapy to prevent gastric cancer (H.pylori antibiotics+proton
pump inhibitors); antioxidants (Vitamins C and E, selenium, β-
carotene); NSAID
what is triple negative breast cancer ?
Triple negative because it lack 3 imporant genes = progesterone , HER2 , estrogen
Hallmarks of cancer cell metabolism
- Deregulate uptake of glucose (ATP without O2 usage) and amino acids
- Use of central carbon metabolism to support biosynthesis
- Use of opportunistic modes of nutrient acquisition (autophagy, micropinocytosis,
endocytosis, entosis) - Expanded need of electron acceptors
- Elevated reliance on oxidative stress protection mechanisms
- Increase demand for nitrogen
- Heterogeneity of metabolic adaptations
- Metabolic interactions with the tumor microenvironment ( mire angigenesis ,other cells become protumeric, more stiffness, reduced activation of T-cells)
- Integration into the whole-body metabolic economy ( they get inputs like glucose and GF and then secrete messages to the whole body for proteolysis, lipolysin ans insulin resistance )
What is the Adaptive utility of the Warburg effect
- Cells generate faster ATP than does the TCA cycle
- Acidification of the extracellular milieu
- Conversion of pyruvate to lactate helps to alleviate the electron load
by directly generating NAD+ for NADH - Increase the capacity to generate glycolytic intermediates to support
biomass
