LM 7.2: Cell Cycle Cancer Flashcards
cancer cells are defined by which two heritable properties?
- they reproduce in defiance of the normal restraints on cell division
- they invade and colonize territories normally reserved for other cells
what’s the mechanism behind how cancer cells proliferate in an unrestrained manner?
they curb the activities of negative regulators of the cell cycle like RB and p53
CDKIs like p16, p21, and p27 that are part of the RB and p53 pathway are also inactivated in cancer
what do RB and p53 do?
they guard the G1-S border and regulate checkpoints in the cell cycle
they’re considered tumor suppressors because lost or inactivation of these proteins would lead to uncontrolled proliferation = cancer!!
what proteins re often over expressed in many cancers?
cyclins and CDKs
what does HPV do?
human papillomavirus is a DNA tumor virus that targets RB and p53 which promotes unrestrained proliferation and cancer
it causes carcinomas of the uterine cervix
HIV makes E7 and E6 which sequester Rb and p53 respectively and prevent their activities
when RB is sequestered by E7, RB can’t inhibit E2F which results in a rise in pro-proliferative gene expression, including cyclin genes
when p53 is sequestered by E6, it results in bypass of a DNA damage checkpoint in the cycle
what is a carcinoma?
a type of cancer that starts in cells that make up the skin or the tissue lining organs, such as the liver or kidneys
like other cancers, carcinomas are abnormal cells that divide without control
they are able to spread to other parts of the body, but don’t always
what’s the general mechanism behind cancer therapies?
they exploit the loss of cell-cycle control and the genetic instability of cancer cells
how do cancer therapies work?
cancer cells don’t have p53
irradiated cancer cells accumulate lots of DNA damage but because they don’t have p53 as a checkpoint, the cell cycle will continue since they lost the DNA damage checkpoint –> eventually they’ll undergo mitotic failure to to the presence of damaged chromosomes which will eventually cause the tumor to regress!
but the bad part is that cancer cells are smart and eventually acquire additional mutations that give them resistance to radiation
what are some of the cancer drugs that target the cell cycle?
- alkaloids
- CDK inhibitors
- antimetabolites
- antitumor antibiotics
what are alkaloids?
cancer drug that targets the cell cycle by preventing chromosome spindle formation and block M phase
these drugs are derived from plants and are used to treat Wilm’s tumor and cancers of the lung, breast, and testes
administered IV
which drugs are alkaloids?
vincristine
vinblastine
what are anti tumor antibiotics?
cancer drug that targets the cell cycle by binding DNA and blocking S phase
used to treat wide variety of cancer including testicular cancer and leukemia
administered IV
which drugs are anti tumor antibiotics?
doxorubicin
mitomycin-C
what are antimetabolites?
cancer drug that targets the cell cycle by interfering with S phase my mimicking nucleotides during DNA synthesis
used to treat tumors of the GI tract, breast and every
administered oral or IV
which drugs are antimetabolites?
6-mercaptopurine
5-fluorouracil
