cancer 4 Flashcards
what trial is designed to determine the safe and appropriate dose?
phase 1
what is phase II?
designed to determine the effectiveness and side effects of the new drug in one type of cancer
what trial tests the effectiveness of new drug and compares it to the best available standard treatment?
phase 3
what is phase 4?
determines the long-term safety and effectiveness of new drug
what is ABL?
protooncogene that codes for a protein that normally functions as a tyrosine kinase
what happens to ABL in CML?
due to its fusion with Bcr protein, the Abl protein kinase becomes constitutively active.
in CML, what is responsible for malignant transformation?
Bcr-Abl fusion protein
what is the treatment option for APL?
All trans-Retinoic Acid
what are the toxicities of Retinoic acid?
- increase in white blood count (leukocyte activation syndrome or retinoic acid syndrome)
what is leukocyte activation syndrome?
involves fever, resp. distress, weight gain, pleural or pericardial effusion
toxicity of Trastuzumab (HERCEPTIN?)
- ventricular dysfunction and congestive heart failure
2. can enhance the cardiac toxicity of doxorubicin
what is the treatment for Non-Hodgkin’s lymphoma?
Rituximab
what is follicular lymphoma?
- a type of Non-hodgkin lymphoma
- mostly affects older adults
- t(14;18)
what is Rituximab?
a chimeric monoclonal antibody with variable region of mice IgG but constant region and Fc portion from human
what is the mech of Rituximab?
- binds to CD20 antigen
how does Rituximab eliminate CD20 positive follicular lymphoma cells by
- direct activation of apoptosis
- complement activation
- cell-mediated cytotoxity
what gene mutation is involved in melanoma?
BRAF mutation found in 45-50% of cutaneous melanomas
what is used for treatment of melanomas harboring BRAF mutations?
Vemurafenib
Vemurafenib is
a BRAF inhibitor
what are two immunotherapy agents for Melanoma?
- ipilimumab
2. Interleukin-2
how does Ipilimumab work?
it functions as a Cytotoxic T-lymphocyte Antigen 4 inhibitor
what is CTLA-4?
a surface receptor present on T cells, functions to down-regulate the cellular immune system –> by inhibiting CTLA-4, ipilimumab is expected to stimulate immune system.
chromosome 22 has
BCR
chromosome 9 has
abl
treatment options for CML?
hydroxyurea or interferon alpha based regimen with allogenic stem-cell transplantation
intrinsic resistance could be b/c
pts with persistent Bcr-Abl kinase activity
Imatinib mesylate is also used for
gastrointestinal stromal tumors (GIST)
GIST harbor activating mutaion gene in
KIT
off-label use of Imatinib is
APL
APL involves what kind of translocation?
15;17
retinoic acid therapy of APL is considered as
earliest example of Molecular targeted therapy
the mech of retinoic acid?
induce differentiation and apoptosis
what is the toxicity of retinoic acid?
leukocyte activation
HER2 mediate effects via
ADCC (antibody dependent cellular cytoxicity)
