Antineoplastics Flashcards
What are the specific checkpoints that cells need to pass for…
G1/S?
G2/M?
metaphase/anaphase?
G1/S: Prepare for synthesis. Are Cell nutrition, size, environment favorable? is all DNA intact?
G2/M: Is DNA completely replicated?
Metaphase/Anaphase: Is all DNA intact? all chromosomes attached to mitotic spindle?
Describe 3 mechanisms of oncogene formation
Start as Proto-oncogene - mut - become oncogene
Point mutation; one amino acid
Gene amplification: extra copies of the mutated gene
Chromosomal Translocations: Proto-oncogene getting fused with another gene that is active.
Describe the hallmarks of cancer
Sustained Proliferative signal evade growth suppressor avoid immune system inducing angiogenesis resisting cell death
Define the 4 goals of cancer drug therapy
- Primary chemo/curative
- ALL, Testicular, AML, Hodgkins
- Primary chemo/control
- Adjuvant therapy. after sx
- Neoadjuvant therapy. b4 sx
What are the general mechanisms of drug resistance to chemotherapeutic agents?
Epigenetics, Drug efflux, DNA damage repair, Cell death inhibition, Epithelial-Mesencymal Transition, Drug target alteration, Drug inactivation
MOA: 6-Mercaptopurine
Converted to Thio-IMP by HGPRT = blocks AMP prod and other stuff with DNA synthesis
MOA: Fludarabine
What cancer tx?
Incorporated into DNA and blocks transcription.
CLL
MOA: Cytarabine
What cancer tx?
Gets incorporated into DNA, messes up DNA polymerase
AML
MOA: 5-fluorouracil
Inhibit Thymidilate synthase, incorporated into DNA/RNA and stops
MOA: capecitabine
Inhibits Thymidylate synthase, incorporated into DNA/RNA stops
MOA: Methotrexate
blocks dihydrofolate reductase. decreased DTTP and purines in DNA/RNA
MOA: Cyclophosphamide
Cause DNA crosslinking, breaks, abnormal base pairs
MOA: Carmustine (BCNU)
What cancer?
Cause DNA crosslinking, breaks, abnormal base pairing
Brain, GI Tumor, Hodgkins Lymphoma
MOA:
Cisplatin
Carboplatin
No alkyl group, but leads to DNA crosslinking
MOA: Doxorubicin
Inhib Topo II, intercalated DNA and changes shape
MOA: Bleomycin
Chelates Iron and Copper and causes DNA breaks
MOA: Paclitaxel
Prevent disassembly of microtubules
MOA:
Vinblastine
Vincristine
Mitotic arrest in metaphase - Prevent microtubule formation
MOA:
Irinotecan
Topotecan
Inhibiting Topo I - no strand repair
MOA: etoposide
Class II Topo inhibitor, double strand DNA breaks
MOA:
Prednisone
Dexamethasone
Decrease Lymphocyte Proliferation
MOA: tamoxifen
What cancer?
Selective Estrogen Receptor Modulator, competetive inhibitor
Breast
MOA: Flutamide
What cancer?
Competetively inhibits testosterone from androgen receptor
Prostate
MOA: Anastrozole
What cancer?
*****
aromatase inhibitor - limits peripheral estrogen production
Breast
MOA: Imatinib
What cancer?
Binds to ABL and causes conformational change - limits ATP binding
CML
MOA: Erlotinib
What cancer?
*****
Binds and inhibits EGFR receptor - limit proliferation
NSCLC, mut on chrom 19,21
MOA: Vemurafenib
What cancer?
BRAF inhibitor, for when it is mutated and always active
Lots of Cancers
MOA: Bevacizumab
Binds VEGF, inhibits angiogenesis
MOA: Trastuzumab
What cancer?
Binds HER2 (EGFR) on extracellular surface. Breast
MOA: Cetuximab
Binds EGFR and stops signaling
MOA: Ipilimumab
What cancer?
*****
Blocks activation of T cells to save for cancer attack.
Blocks CTLA-4 binding B7
MOA: Nivolumab
What cancer?
PD-1 inhibitor
Melanoma
MOA: Asparaginase
What cancer?
*****
Hydrolyzes plasma L asparagine into aspartate, starving cancer cells
Childhood ALL
MOA: Leucovorin
Reduced Folic acid
Used with MTX to reduce toxicity
MOA: Mesna
Used to reduce damages caused by toxic metabolites of cyclophosphamide
MOA: Filgrastin
Prevents myelosuppression when used with Paclitaxel
What are the mechanisms by which cancer cells become resistant to: Methotrexate? Cyclophosphamide? 6-Mercaptopurine? 5-Fluorouracil? Vinblastine? Vincristine? Doxorubicin? Topotecan? Irinotecan? Cytarabine? Fludarabine? Alkylating Agents? Imatinib? Cetuximab?
Methotrexate: Duplication of DHFR, reduced transport
Cyclophosphamide: p53 mut, Inc MGMT, accel DNA repair, reduced uptake
6-MP: acquired deficiency in HGPRT
5-FU: amplification of Thymidylate synthase
Vinblastine: causes myelosuppression
Vincristine: less myelosuppression, more neurotoxicity
Doxorubicin: ?
Topotecan: ?
Irinotecan: ?
Cytarabine: Lose Deoxycytadine kinase, reduced transport, cytadine deaminase
Fludarabine: Decreased activity of Deoxycytadine Kinase, drug efflux
Alkylating Agent: p53 mut, inc MGMT, accel DNA repair, reduced uptake
Imatinib: Pt mutation in ABL
Cetuximab: mut in RAS
What drugs lead to the following adverse effects: Neuropathy hypersensitivity reaction caridac toxicity nephrotoxicity Pulmonary toxicity bladder toxicity cerebellar syndrome endometrial cancer
Neuropathy: Vincristine, Cytarabine, Cisplatin, Paclitaxel
Hypersensitivity rxn: asparaginase, paclitael, cisplatin, carboplatin
Cardiac toxicity: Doxorubicin, trastuzumab
Nephrotoxicity: cisplatin, methotrexate
Pulmonary Toxicity: MTX, bleomycin
Bladder toxicity: Cyclophosphamide
Cerebellar syndrome: Cytarabine
Endometrial Ca: Tamoxifen
what agents/tx are used to mitigate use of... Methotrexate cisplatin doxorubicin paclitaxel cyclophosphamide
MTX: Leucovorin
Cisplatin: water and saline
Doxorubicin: Epirubicin has less cardiotoxicity
Paclitaxel: Filgrastim for myelosuppression
Cyclophosphamide: Mesna
What drugs used in curative chemo for Testicular Cancer?
BEP: Bleomycin, Etoposide, Cisplatin
What drugs used in curative chemo for Hodgkins lymphoma?
MOPP: Mechlorethamine, Vincristine, Procarbazine, Prednisone
ABVD: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine
What are the drugs in the Antimetabolite category?
6-MP, Fludarabine, Cytarabine, 5-FU, Capecitabine, MTX
What are the drugs in the Alkylating agents category?
Cyclophosphamide, Carmustine
Cisplatin, carboplatin (both non classical)
What are the drugs in the Cytotoxic antibiotic category?
Doxorubicin, Bleomycin
What are the drugs in the Natural product agents category?
Paclitaxel, vinbalstine, Vincristine, Irinotecan, Topotecan, Etoposide
What are the drugs in teh Hormone agonists/antag category?
Prednisone, Dexamethasone, Tamoxifen, Flutamide, anastrozole
What drugs are in teh small molecule tyrosine kinase inhibitors category?
Imatinib, erlotinib, vemurafenib
What drugs are in teh Monoclonal antibodies category?
Bevacizumab, trastuzumab, cetuximab, ipilimumab, nivolumab
