cancer part 3 Flashcards
What are plants’ Alkaloids?
High molecular weight, highly lipophilic natural products
State the two types of plant Alkaloids
Microtubule inhibitors
Topoisomerase inhibitors
State how plant alkaloids act as an anti-cancer agent
Disrupt balance between polymerised and depolymerised microtubules
Cell cycle specific
list the two classes of drugs that are microtubule inhibitors
Vinca alkaloids and Taxanes
Vinca alkaloids are derived from?
periwinkle plant
List examples of drugs that are vinca alkaloids
Vincristine, vinblastine, vinorelbine
what is Vinblastine indicated for?
metastatic testicular carcinoma and lymphomas
VB is administered with bleomycin/cisplatin
What is the Vincristine indicated?
Childhood ALL- Acute lymphoblastic leukaemia; Wilm’s tumour, lymphomas
What is Vinorelbine indicated for
Advanced non-small cell lung cancer
What is the mechanism of Vinca alkaloids?
Cell cycle dependent - mitosis is blocked in metaphase
GTP-dependent binding to tubulin - blocks polymerisation - stops microtubule formation
Dysfunctional spindle apparatus - frozen in metaphase - chromosomal segregation stopped
State the side effects of Vinca Alkaloids
N/V/D - esp Vincristine
Alopecia
Extravasation
VB - myelosupression
VC - peripheral neuropathy
List the examples of Taxanes
Paclitaxel
Docetaxel
What is taxol?
derivative of precursors found in yew tree - first member of taxane family studied
State the uses of Taxanes
Advanced ovarian and metastatic breast
Also used in
Small cell lung cancer
Many combinations
State how mitosis is blocked by paclitaxel?
Usually, stable tubulin molecules stack and fail to depolymerise, cell remains frozen in metaphase
State the mechanism of action of Taxanes
Paclitaxel binds tubulin reversibly
Unlike vinca alkaloids it promotes polymerization/ stabilization of tubulin
Shifts equilibrium - formation of microtubules
Overly stable tubules - dysfunctional, cell stopped in metaphase
Cell death
Facts about Eribulin
synthetic analogue of potent antitubulin agent halichondrin B.
Halichondrin B is a natural product from a rare Japanese sponge.
third line treatment for cancer
Orally administered
State the side effects of Eribulin
low incidence of peripheral neuropathy.
Neutropenia
Fatigue
State the difference between vinca Alkaloids and Taxanes?
Taxane inhibit depolymerization while vinca Alkaloids inhibits polymerization
State the name of orally available microtubule inhibitor currently in trials for advanced prostate and breast cancer?
Sabizabulin
State what topoisomerase 1 inhibitor does?
Topoisomerase 1 induce transient break in single strand and prevent resealing
State the role of topoisomerase II inhibitor?
It induces transient break in DNA double strand and prevent resealing
State the Mechanism of action of topoisomerase inhibitors
inhibits the cycle (break and resealing) of TOPO at the DNA break point.
It inhibits DNA closing or resealing reaction by forming stable cleavable-TOPO-DNA complex.
It forms indirect protein-associated single and double strand break.
List examples of drugs that are topoisomerase 1 inhibitors
Topotecan
Irinotecan
