anti-cancer Flashcards
genes that are transformed to a hyperactive state and by virtue of that, lead to cancer. When activated cancer results (inactivated is death)
Oncogene
when activated cancer results (inactivated is death)
(they control parts of growth that you normally want ON) when inactivated cancer results (activated is death)
Tumor suppressor:
when inactivated cancer results (activated is death)
- Cells can be stimulated into growth cycle by Growth Factors that trigger increased _, starts timed increases in other cyclins in order to prepare for and carry out mitosis
- New agents seek to block signals that raise Cyclin D in cancer
Cyclin D
• Cyclin D/CDK
- Cancer results from imbalance between Cell growth and Cell death
- Growth factor receptor _ signaling can stimulate mitosis via Cyclin D
- Growth Factor signaling can repress apoptosis and promote cell survival
- Anticancer drugs may inhibit mitosis and/or cause necrosis or apoptosis to reduce a cancer
tyrosine kinase
• Tyrosine kinase signaling can stimulate mitosis by increasing _
o Causing cells to enter cell growth cycle
• Tyrosine kinase signaling can also inhibit cell death
• Many agents act on steps of kinase receptor signaling
o Receptor Tyrosine Kinases, Non-receptor Tyrosine kinases, PI-3 kinases, serine/threonine kinases
• Some agents stimulate or block steroid hormone receptors that regulate mitosis and death of specific cancers
• Antibodies can target specific cancer cell molecules
o Attract killer cells or deliver toxic agents
Cyclin D
- Cancers evolve to produce resistant cells
- Development of resistance can be reduced by using _
- Treatments are repeated to keep killing cells that escape or have damage
- Preferable to use different mechanisms
different drugs/mechanisms
Try to stop cell division and kill cell by disrupting biochemistry and key enzymes and proteins
cytotoxic
_ is the most common side effect of cytotoxic anticancer therapeutics
(Thrombocytopenia increased bleeding time &&& Immunosuppressionstopping of leukocyte production…mainly neutrophils)
Myelosuppression
A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets
Know how DNA damage causes necrosis, apoptosis and inhibition of mitosis
- Causes acute metabolic reaction involving enzyme _
a. Excess DNA activates it
i. it consumes NAD + ATP and thus Kill cell - DNA breaks activate kinase signaling inducing_ (inhibitors of cyclin dependent mitosis, activate apoptosis)
a. Growth arrest by cyclin D inhibitors -> death by intrinsic path
PARP
- P53
• Resembles Folate
• Inhibits dihydrofolate reductase – depleting tetrahydrofolate
o Can’t transfer methyl to dUMP –> No synthesis of TMP
Blocking DNA synthesis
• Separately inhibits purine ring synthesis
o Reduces DNA and RNA synthesis
methotrexate
_ is a base analog that is ultimately activated to a version attached to deoxyribose forming FdUMP
- FdUMP inhibits thymidylate synthase
- Lowers TMP and blocking DNA synthesis
5-fluoruracil
Vincristine or Paclitaxol
_ inhibits formation of microtubules (tubulin polymerization)
_inhibits tubule disassembly.
Both prevent separation of chromosomes at mitosis
vincristine - inhib formation
Paclitaxol inhib disassembly
Induce ROS that damage DNA with PARP and P53 consequences -> apop
Radiation and photodynamic agents
they induce reactive oxygen species that damage DNA with the associated PARP and p53 consequences.
DNA damage is sensed by _ and is turned on as a part of normal repair using NAD. Over activation of PARP enzyme leads to no more NAD in the cell. So in order to make more NAD, cell uses ATP. ATP depletion will eventually cause cell to die (necrosis
PARP
DNA breaks activate kinase signaling including p53turns on the expression of proteins that inhibit _ THIS WILL STOP MITOSIS & PROMOTE APOPTOSIS
cyclin dependent kinases (CDK)
