31/01/2025 11:35:43
Pharmacology
CCNS drugs (cell-cycle non-specific)
--> Anticancer drugs that can sterilize tumor cells regardless of whether they are
cycling or resting in G0 Phase
--> Less-selective toxicity and cause damage to healthy cells.
--> More damage to healthy cells
N for non-proliferating, normal cells,
_____ drugs are used for recruitment and induce non-proliferating clonogenic
fraction to enter into cell cycle
CCNS --> Causes increased vulnerability to CCS agents afterwards since cells are
actively dividing.
Adverse effects of CCS drugs
The most rapidly proliferating normal cells are likely to suffer toxicity along with the
tumor cells, but the damage is mostly reversible
--> Bone marrow resumes production
--> Hair regrows,
--> gut and oral mucosa recover.
Abortion and infertility are irreversible.
Broad adverse effects
CCNS drugs
Cisplastin
Side effects: Vomiting, nephrotoxicity
Doxorubicin
I <3 rubics cubes
Side effects: Cardiotoxicity
Dexrazoxane: Limits toxicity
Vincristine
Crest = the periphery
Side effects: Peripheral neuropathy
Bleomycin
Pulmonary fibrosis
Surgical debulking
A form of selective toxicity, that allows for large portion of tumor cells to re-enter cell
cycle and proliferate, thus causing death.
Clenogenic fraction (non-growing or non-dividing) are unaffected.
Radiation and cell-cycle non-specific cytotoxic drugs are more broad and cause
MORE COLLATERAL DAMAGE.
Oncolytic viral therapy
One that preferentially infects and kills cancer cells.
, 31/01/2025 11:35:43
Selectively infects lyses only in primary and metastatic cells of that type (eg multiple
myeloma)
Multimodal therapy
Chemotherapy, radiation, surgery
Selective toxicity
Selectively eradicate neoplastic cells without damaging host (normal) cells.
CCS are more selectively toxic, but they cannot kill clonogenic fraction cells like
CCNS agents.
CCNS agents are used for recruitment (to induce non-proliferating clonogenic
fraction to cycle)
CCS+CCNS deplete growth fraction as recruited
Clonogenic fraction
G0 cells (undividing). Targeted by CCNS drugs
Cytotoxic kinetics
Cancer cells grow exponentially and cancer chemo uses highest tolerated dose
REGARDLESS OF TUMOR SIZE.
Rate killed is logarithmic (first-order kinetics) therefore 3-log dose will decrease
cancer cell population by 3 orders.
The intensity required to reduce a large tumor and a small tumor to half their size is...
THE SAME
Curative
Tries to cure cancer. Toxicity is acceptable
Palliative
Tries to reduce tumor burden to improve disease-related suffering. Toxicity is
unacceptable.
Induction (neoadjuvant) phase
INITITAL REGIMEN. STEP 1!!!
Decrease tumor burden by recruiting clonogenic cells into growth fraction. Occurs
prior to tx with other modalities
Intensification phase
STEP 2!!!
Achieve remission by adding more drugs to regimen, increasing dosage, increasing
duration.
Consolidation
Repeated doses of same combination of drugs to maintain remission.
Cisplastin, Cyclophosphamide
Alkylating agents
Covalently cross-link DNA bw and within strands
Bleomycin, doxorubicin
Antibiotics
Intercalation bw base pairs in DNA or RNA
METhotrexate
(pure meth)
Pharmacology
CCNS drugs (cell-cycle non-specific)
--> Anticancer drugs that can sterilize tumor cells regardless of whether they are
cycling or resting in G0 Phase
--> Less-selective toxicity and cause damage to healthy cells.
--> More damage to healthy cells
N for non-proliferating, normal cells,
_____ drugs are used for recruitment and induce non-proliferating clonogenic
fraction to enter into cell cycle
CCNS --> Causes increased vulnerability to CCS agents afterwards since cells are
actively dividing.
Adverse effects of CCS drugs
The most rapidly proliferating normal cells are likely to suffer toxicity along with the
tumor cells, but the damage is mostly reversible
--> Bone marrow resumes production
--> Hair regrows,
--> gut and oral mucosa recover.
Abortion and infertility are irreversible.
Broad adverse effects
CCNS drugs
Cisplastin
Side effects: Vomiting, nephrotoxicity
Doxorubicin
I <3 rubics cubes
Side effects: Cardiotoxicity
Dexrazoxane: Limits toxicity
Vincristine
Crest = the periphery
Side effects: Peripheral neuropathy
Bleomycin
Pulmonary fibrosis
Surgical debulking
A form of selective toxicity, that allows for large portion of tumor cells to re-enter cell
cycle and proliferate, thus causing death.
Clenogenic fraction (non-growing or non-dividing) are unaffected.
Radiation and cell-cycle non-specific cytotoxic drugs are more broad and cause
MORE COLLATERAL DAMAGE.
Oncolytic viral therapy
One that preferentially infects and kills cancer cells.
, 31/01/2025 11:35:43
Selectively infects lyses only in primary and metastatic cells of that type (eg multiple
myeloma)
Multimodal therapy
Chemotherapy, radiation, surgery
Selective toxicity
Selectively eradicate neoplastic cells without damaging host (normal) cells.
CCS are more selectively toxic, but they cannot kill clonogenic fraction cells like
CCNS agents.
CCNS agents are used for recruitment (to induce non-proliferating clonogenic
fraction to cycle)
CCS+CCNS deplete growth fraction as recruited
Clonogenic fraction
G0 cells (undividing). Targeted by CCNS drugs
Cytotoxic kinetics
Cancer cells grow exponentially and cancer chemo uses highest tolerated dose
REGARDLESS OF TUMOR SIZE.
Rate killed is logarithmic (first-order kinetics) therefore 3-log dose will decrease
cancer cell population by 3 orders.
The intensity required to reduce a large tumor and a small tumor to half their size is...
THE SAME
Curative
Tries to cure cancer. Toxicity is acceptable
Palliative
Tries to reduce tumor burden to improve disease-related suffering. Toxicity is
unacceptable.
Induction (neoadjuvant) phase
INITITAL REGIMEN. STEP 1!!!
Decrease tumor burden by recruiting clonogenic cells into growth fraction. Occurs
prior to tx with other modalities
Intensification phase
STEP 2!!!
Achieve remission by adding more drugs to regimen, increasing dosage, increasing
duration.
Consolidation
Repeated doses of same combination of drugs to maintain remission.
Cisplastin, Cyclophosphamide
Alkylating agents
Covalently cross-link DNA bw and within strands
Bleomycin, doxorubicin
Antibiotics
Intercalation bw base pairs in DNA or RNA
METhotrexate
(pure meth)
