AntiCancer Flashcards
Explain the Cancer Pathophysiology / Hallmarks,cell cycle , checkpoints
—Hallmarks : they are 6 main hallmarks thats appear on Cancer cells :
1-Uncontrolled proliferation
2-Resistance to Apoptosis
3-induction of Angiogenesis: they can secrete growth factors such as VEGF which let these malignant cells induce blood vessels
4-invasion and metastasis
5-Avoiding immune distraction
6-loss of function
—————-
-Cell cycle : its cycle for cell division in normal cases and has several phases :
-Phase 0: the cell in the resting state and its called G0 , then the cell receives Mitogenic signal to start the cell cycle for cell proliferation
-Phase 1: its called G1 which is the cell will increase in size
-Phase 2: this Phase called S phase ( Synthetic ) which is The cell Duplicate its DNA
-Phase 3: its called G2 which is the cell increasing in size again
-Phase 4: This Phase called M phase ( Mitosis ) which is contain 4 Sub-Phases
4.1 : Prophase ( Creating Sentrosoms )
4.2 : Metaphase ( Mitotectic spindles)
4.3 : Anaphase ( pulling the mitotic spindles)
4.4 : Telophase ( mitosis )
——
-Location : G1,S,G2
-Checkpoints: these checkpoints are Proteins Complex and there Function to check the Phases of The cell cycle if there is any abnormalities they will signal the cell to stop the the Cell cycle , And they are done by types of proteins:
1-Ve+ Regulators :such as
1.1 Cyclins and CDKs ( cyclins-dependent kinases )
1.2 Growth factors thats Acts on protein kinase
1.3 Signaling proteins such as : Ras , Raf
2- Ve- regulators :
2.1 P53
2.2 Brca1 , Brca 2
-NB! If there is mutation of the + regulators the cell cycle will keep dividing without entering the resting state , and if there is a mutation in the - regulators the cell cycle will keep dividing even with abnormalities of the cell
Explain the : Growth Factors , Telomere/Telomeres
—Growth factors: they are proteins Belong to Proto-Oncogens , when the mutation they becomes Oncogenes Examples:
1-IGF : insulin GF
2-FGF : Fibroblast GF
3-EGF : Epidermal GF
4-PDGF : platelets dried GF
5-VEGF : vascular Ednothelial GF
- in the Cancer cells , the cell will keep secreting these GF and these GF will bind to tyrosine kinase receptors and activate a series of proteins till reach protein in the DNA which will activate proliferation machinery program which will lead to uncontrolled proliferation in case of cell cancer
——————-
— Telomere and Telomeres : the Telomere is found in the end of each Chromosome with each division its decreased ( its protective mechanism for inhibiting the uncontrolled cell division ) but in case of Malignant cells they activate the telomeres which will increase the telomere leading to uncontrolled proliferation
What is the General side effect of the AntiCancer Drugs
- they are 7 :
1-Myelosuppration
2-impaired Wound healing
3-Alopecia ( hear loss )
4-hepatotoxic
5-Sterility
6-damage of GI epithelium
7-tetrogenicity / Carcigenicity
Explain Alklyting agents , Drug groups , mechanism , pharmacokinetics, specific side effect , uses
—Drug groups :
1-Nitrogen mustard : Cyclophosphamide tab/Amp
2-Nitrosoureas : Carmustine Amp
3-Other : Busulfan tab
—Mechanism: produce highly reactive intermediates which transfer Alkyl group to cellular micro molecules , At the Position 7th of guinin forming covalent bond which lead to DNA cross linking > resulting of inhibition of mitosis or even apoptosis
—Pharmacokinetics: Cyclophosphamide most alkylting agent used and its pro-drug which it’s required biotransformation in the liver by CYP450 to become active form
-Specific side effect :
1-Hemorrghic cystitis : caused by the metabolite called acrolein and can be prevented by increasing fluid intake or sulfhydrl donor such as
N-Acetlycysteine which is washing the bladder from this toxic form
—uses :
1-AntiCancer drug in most types of cancer
2-As immunosuppressants: such as RA,SLE duo to cross linking in T-cells which is in most cases its the reason of Autoimmune disease
Explain Antimetabolite , Drug groups , general/specific mechanism , side effect , uses , drug interaction
—Drug groups :
1-Folic Antagonist: Methotrexate tab/Amp
2-Purine Analog: MercaptoPurine,Azathioprine tabs
3-Pyrimidine analog : Fluorouracil amp
—General mechanism: Antimetabolites are Analogous related to normal components involved in nucleic Acid synthesis, they comptatevly inhibit utilisation of physiological substrate leading to stop mitosis duo to wrong substrate
—specific mechanism of methotrexate : its folic acid antagonist which is interferes with folic acid which is essential for synthesis DNA cell division in Phase S
-Specific side effect :
1-Megaloblast anemia
2-mucosal ulceration
-uses:
1-AntiCancer drug
2-Autoimmune suppressant
——-
-Specific mechanism of
6-Mercaptopurine : interferes with Purine nucleotide ( Adenin , Gunini ) synthesis thus inhibiting DNA and RNA synthesis in Phase S
-Specific side effect :
1-the enzyme
Thiopurin S-methyltransferes Convert 6-MP into non toxic form people with this enzyme deficiency are subjected to sever myelosuppration
2-The enzyme Xanthin Oxidase breaks down 6-MP , Using a drug such as Allopurinol ( for gout ) which is Xanthin oxidase inhibitor lead to sever toxicity ( Drug interaction )
Explain AntiCancer antibiotics , mechanisms, main adverse effect
—Drugs :
1-Doxorubicin Amp
-mechanism: its bind to DNA and DNA gyres thus inhibit DNA and RNA synthesis
-main adverse effect : cardio toxicity
—-
2-Actinomycin D Amp
-mechanism: its inhibit transcription By binding to DNA at the transcription initial complex and preventing Elongation of RNA chain by RNA polymerase
-main side effect : black stool , hemtoureia
Explain microtubules inhibitors ( vinca alkaloids ) / mechanism , specific side effect
—Drugs :
1-Vinblastine
2-Vincristine
-mechanism: they are cell cycle specific , they bind to microtubules system ( mitotic spindles ) during the Metaphase and cause Metaphase arrest which lead to prevent cell division
-Specific side effect :
1-Vinastine : more BM depression but less neuropathy
2-Vincristine : More peripheral Neuropathy but less BM depression
Explain Hormones and there Antagonists in Anticancer , Antiestrogen/drugs,mechanisms,
Antitesteron/drugs,mechanism
-Some Tumours are hormones dependent such as Breast /Prostatic Cancer
—Antiestrogen
-Drug and its mechanism:
1-Tamoxifen tab : its an Oestrogen Antagonist in the Breast but it’s ago so in the uterus and BM
-Side effect : DVT
-uses : breast cancer in female premenopausal
2-Anastrozole Tab : its competitive inhibitor of Aromatase which is responsible for production of Oestrogen from the adrenal cortex And prephrial tissue .
-uses : for breast cancer in female that Postmenopausal which Estrogen receptors positive
——AntiTesteron:
-Drug: Flutamide Tab
-mechanism: its potent blocker of testosterone receptors
-uses : advanced prostatic Cancer
-Specific side effect : Hepatotoxic
Explain the Monoclonal Antibodies for Anticancer, Drugs , mechanism , Target , Uses
-NB1 they Are MABs designed to bind to specific Target on the surface of Cancer cell or immune cells , and they are given by IVI
-mechanism: They block the GF receptor which lead to Arresting proliferation and triggering apoptosis of tumour cells , and recurrent
NK-Cells that Have cytotoxicity, bind complement leading to direct cell toxicity
-Drug,Target,Uses :
1-Rituximab , CD20 ,
B cell non-Hodgkins lymphoma
2-Ibritumomab ,CD20 .
B cells non-Hodgkins lymphoma,
Chronic Mylogenous leukaemia
3-Trastuzumab , EGF receptor , breast cancer
4-Bevacizumab , VEGF ,
Colorectal cancer ,
Breast Cancer ,
,Non- small cell lung cancer
Explain Tyrosine kinase inhibitors, Drug , mechanism, Target , side effect , Uses
-NB1 : they are small molecules used to target singling pathway kinase of GF such as EGF ,PDGF thus preventing uncontrolled cell proliferation
-Drugs and its target :
1-Imatinib : its inhibit The BCR-ABL tyrosine kinase , this inhibition blocks proliferation and promotes apoptosis in BCR-ABL positive cell line
-side effect : fluid retention and hepatotoxic
-uses :
1-to Treat Philadelphia Chromosome positive which is chronic mylogenous leukaemia
2-Erlotinib + Gefitinib : Target EGF in tyrosine kinase receptor
-Uses : non small cell lung cancer
3-Lapatinib : Target EGF in tyrosine kinase receptor
-uses : breast Cancer
