Dr. Malkus Video on Cancer Detection
A single strand of DNA is about 3 feet long
There are 5 X 1019 cells in the human body
DNA in a single human stretches beyond the sun
Your body makes about 8 cancer cells per day but your immune system
recognizes these and takes care of them.
Why can we send a person to the moon but can’t cure cancer? Because it is
easier to put a man on the moon than to cure cancer.
Dr. Malkus’ Premise: We could cure cancer if we could detect it sooner.
She wanted to find a biomarker that could identify the presence of cancer.
Present biomarkers do not distinguish between cancerous cells and
normal cells early in disease. They only work when cancer is far along.
Dr. Malkus’ Dream: Screen people for cancer during a typical physical exam by
taking a blood sample and checking blood for cancer factor.
Use the same technology to monitor people who are currently undergoing
treatment for cancer
This will allow the doctor to monitor levels of cancer easier and adjust
treatment as necessary.
Currently the treatments cannot be monitored and it takes 3-6 months to
see the effects of the treatment on the patient.
We also need new therapies for treating cancer. Current treatment kills ANY
growing cell (cannot distinguish between rogue cancer cell or normal cell).
This is why chemotherapy causes people to lose their hair (hair follicles
always growing), fingernails stop growing, and not be able to eat shortly
after treatment (cells in digestive tract always being replaced).
Genomics-field of genetics that checks normal and cancer cell DNA to identify
what is different.
Dr. Malkus hypothesis: Altered DNA replicator/repair mechanism leads to
genetic damage
Dr. Malkus and her team focused on the DNA protein responsible for
replicating DNA since that is where the mistakes are made. Typical
chromosomes take about 3 hours to replicate.
She found the protein in 1990 and called it a DNA synthesome (same as DNA
polymerase)
Hypothesis for the grant she wrote: A change in a component of the synthesome
may be responsible for lack of accuracy of DNA replication.
She isolated the DNA synthesome from normal cells and from cancer cells.
Data said that cancerous synthesome caused more mutations.
DNA synthesome is mutagenic (causes mutations)
Found a trimer (3 polypeptides in a ring) she coined “The Ringmaster” because
everything else attaches to it when synthesizing DNA.
She ran PCNA through a gel electrophoresis form a normal patient and got only
the basic form.
When she ran a PCNA from cancer cells there were two forms (one faint
basic/normal form and one strong acidic form)
Breast cancer has the acidic form
In a blind study (she didn’t know the difference between patients with cancer and
those without) her detection of the acidic form was 100% accurate for cells from
cancer patients.
Benign tumors (harmless type) do not have the acidic form of PCNA.
When attempting to detect the change in DNA for coding for PCNA, there were
no differences between normal cells and cancerous cells.
the problem must be a post-translational mutation
She took blood from a stage 3 breast cancer patient and found the acidic form of
PCNA.
Currently, commercial antibodies used to detect PCNA see both the normal and
the cancerous PCNA equally.
her antibody only sees the cancerous PCNA
Normal detection of cancerous cells up to now relies on visual inspection of a cell
smear on a slide with brown cells which are the cancerous cells.
With her new antibody technique, they can see single cells of cancer rather than
cells after they have caused the damage.
Goals:
1. To create an antibody detection screen for patients at a normal doctors
visit to detect the cancer sooner.
2. To find a marker that can be used to bind to the active site of the PCNA
and render it useless so that no more cells can be copied with that acidic
form of PCNA.