Anticancer Therapies Radiation and Drugs Flashcards
Key properties of cancer cell (2)
They reproduce without regard to the normal restraints on cell growth and cell division
They invade and colonize areas normally reserved for other cells
Tumors or neoplasms are abnormal cells that (2)
grow (increases in mass) and proliferate (divides)
Tumors are considered — if the neoplastic cells do not become invasive
benign
Tumors are considered cancerous if it acquires the ability to invade surrounding tissue at which point it is has become —
malignant
Malignant tumors often, as a consequence of
their invasiveness, produce cells that break
out of their primary site and form secondary
tumors at other sites called —
metastases
is a single mutation sufficient to cause cancer?
no
inherited mutations confer increased…
risk of developing cancer
potential risk factors (5)
radiation exposure UV light from the sun chemicals (carcinogens) life style (smoking, certain diets) viruses (EBV, HIV, HPV)
overall incidence of cancer increases with
age
During the cell-cycle the cell has scanning
mechanisms to detect DNA damage and either
(2)
repair the damage or result in cell-cycle arrest
or cell death (apoptosis)
A key mechanism in the cellular response to
DNA damage is mediated by the protein, —
p53
Improved cancer survival rates has been achieved through
combination therapies that are the standard of care today
In addition to the battery of drugs, (2) remain an effective (co-)treatment for many forms of cancer
surgical removal of the tumor and radiation therapy
The basic strategy for treating cancer with
either drugs or radiation is to
induce so much
damage to the tumor cells via DNA damage
(primarily) to prevent them from dividing and
induce cell death
The unfortunate side-effects result from the
same damage potentially occurring in
normal cells
External Beam Therapy
Uses a machine to send high energy beams from outside the body to the tumor area
Internal Radiation Therapy
Radioisotope given internally, radiation generally only travels a short distance depending upon the isotope and its energy
Radiation induces — —, which leads
to — —
DNA damage
cell death
Photon therapy (X-ray/Gamma rays): works either by (2)
direct ionization of atoms in the DNA chain or indirectly by ionization of water to form hydroxyl radicals that can then damage DNA
— — generate energies of 20-150 kV, while most X-ray energies in radiation therapy run in the range of 1-25 MV
Diagnostic X-rays
Other photon beams derived from iridium-192, cesium-137 or cobalt-60 generate — rays with an energy range of 300 keV -1.5MeV
gamma
Charged Particle or Proton therapy
uses a particle accelerator to beam high-energy particles (protons or carbon, boron or neon nuclei)
advantage of charged particle or proton therapy
Better ability to precisely localize the radiation dosage and less damage to surrounding, healthy tissue
Doxorubicin hydrochloride (adriamycin) (2)
Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis
Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids
Bleomycin sulfate (1)
forms complexes with iron that
reduce molecular oxygen to superoxide and hydroxyl radicals
which cause single- and double-stranded breaks in DNA
Cisplatin (1)
forms highly reactive, charged, platinum
complexes which bind to nucleophilic groups such as GC-
rich sites in DNA, inducing intrastrand and interstrand
DNA cross-links, as well as DNA-protein cross-links
Methotrexate (1)
inhibits the enzyme
dihydrofolate reductase, resulting in inhibition of purine
nucleotide and thymidylate synthesis
Vinblastine (1)
Vinblastine binds to tubulin and inhibits
microtubule formation, resulting in disruption of mitotic
spindle assembly and arrest of tumor cells in the M
phase of the cell cycle.
Vincristine (1)
Vincristine binds irreversibly to microtubules and spindle
proteins in S phase of the cell cycle and interferes with the
formation of the mitotic spindle, thereby arresting tumor cells
in metaphase.
Prednisolone (2)
binds to and activates specific nuclear receptors,
resulting in an altered gene expression and inhibition of
proinflammatory cytokine production
stimulates apoptosis in sensitive tumor
cells populations.
Immunotherapy is a treatment designed to (3)
induce, enhance or suppress the immune response
Most applications are designed to stimulate a
person’s own immune response to destroy cancer cells that have escaped normal immune surveillance
Opdivo and Keytruda target
PD-1 on T-cells (also highly expressed on some type of tumors)
Opdivo and Keytruda target PD-1 on T-cells (also highly expressed on some type of tumors). It has been shown to help shrink or slow growth of tumors such as (3)
melanoma, non-small cell lung cancer, Hodgkin lymphoma, others
Opdivo and Keytruda target PD-1 on T-cells (also highly expressed on some type of tumors). It has been shown to help shrink or slow growth of tumors such as (3)
melanoma, non-small cell lung cancer, Hodgkin lymphoma, others
PD-1 is part of an immune checkpoint control system that keeps immune cells from
attacking “self”
CML
Chronic Myelogenous Leukemia
Leukemia characterized by
increased
production/growth of myeloid cells in the bone
marrow that then circulate in the blood
what is CML. caused by
a chromosomal translocation called the Philadelphia chromosome
the translocation creases a
fusion gene/protein between the BCR and ABL gene
fusion protein is a
tyrosine kinase
long term survival rates of CML
> 95%
