Cancer II Flashcards
Driver Mutations
Found in all cancers regardless of heterogeneity.
Passenger Mutations
Mutations that vary cell-cell within the same cancer phenotype.
Know the various ways that genes can be made overactive
Deletion or point mutation in coding sequence- leads to hyperactive protein made in normal amounts.
Regulatory mutation- leads to a normal protein being greatly overproduced (ex. cMyc).
Gene amplification- leads to a normal protein being greatly overproduced, usually through genetic recombination mechanisms.
Chromosome rearrangement- leads to normal protein being greatly overproduced or a hyperactive fusion protein (ex. Philadelphia Chromosome).
Another way is the mutation of the growth factor EGF, removing its regulatory unit to form a constitutively active form that cannot be turned off.
Explain why epigenetic gene silencing is frequently associated with cancer.
Because it turns off tumor suppressor genes.
Describe the role of Polycomb group proteins in gene silencing and possible roles in tumor progression.
Polycomb group proteins shut off tumor suppressor genes (acts as a mutation). It also is involved in the methylation of Histones at H3K27 which makes the histone return to heterochromatin leading to a silenced gene.
Gleevec
Inhibits Bcr-Abl tyrosine kinase by competitively binding to it.
Provide an example of immunotherapy in tumor destruction
Cancer cells are protected by an immunosuppressive environment because they bind the inhibitory regions on the T-cells.
Explain why the existence of redundant pathways may result in treatment failure.
Redundant pathways exist for cell division, resistance to apoptosis, metastasis and angiogenesis, and may be activated by a feedback mechanism on inhibition of a particular pathway. Therefore, inhibition of a single driver mutation is not sufficient to “cure” the cancer. In most cases, one needs to inhibit multiple pathways in combination.
