American researchers published in Science Advances results
the first case of prescribing personalized therapy to a patient with colorectal
cancer, picked up with the help of flies, fruit flies. Analysis of mutations in the tumor allowed
create for him an individual model of gut cancer on a fruit fly and pick up on
flies an unexpected combination of drugs that ultimately helped the patient.
According to researchers from medical school
Icana Mount Sinai Medical Center (USA), 53 year old patient with
metastatic bowel cancer was unsuccessfully treated with two courses
chemotherapy. DNA was isolated from a sample of his tumor and analyzed for the presence of
onco-associated mutations. Total in the tumor, compared with DNA from the blood, was found
over a thousand mutations, however, the researchers were able to select the nine most
significant that would affect the main signaling pathways. There are mutations in
KRAS oncogene which
associated with almost half of intestinal tumors, and mutations that suppress the main
tumor suppressor genes.
Since the main cellular signaling pathways
conservative in all animals, the researchers were able to reproduce the genetic characteristics of the patient's tumors on the fruit fly. To do this in the fly homologue
KRAS gene introduced such
the same mutation as in the patient, and the expression of tumor suppressors was suppressed using miRNA,
synthesized only in the intestinal cells of flies.
After creating an individual mushroom tumor model, the researchers
sifted through a library of cancer approved drugs in search of
drugs that would increase the survival of transgenic flies. From the first attempt
there was no such substance. Then the researchers chose an inhibitor drug
kinases that act on cells with mutations in the KRAS gene (trametinib) and began to combine
it with other drugs, and not only with approved drugs, but also with those that
showed at least some anti-cancer activity on the models. It turned out that
Trametinib works in combination with bisphosphonate drugs that
usually prescribed to maintain bone mineral density (ibandronate and
zoledronate). According to the results of the experiment, the council of oncologists decided to appoint a combination to the patient
trametinib with zoledronate.
A new combination of drugs helped, after three months
therapy, the volume of cancer foci in men decreased by half. Unfortunately,
after that, the progress in the treatment stopped. Total experimental treatment
lasted 11 months, after which the patient was prescribed regorafenib (another inhibitor
kinase) as a fourth-line therapy.
Despite only partial success of treatment, the authors
emphasize that they have managed to create the most complex model for today that reproduces
genetic landscape of the tumor. Other Drug Screening Methods
involve the creation of a tumor culture in vitro or grafting it to mice is more
an integrated approach, however, it can be much more time consuming and costly
We have previously told how to
scientists suggested using a personalized model of colorectal cancer
fish Danio rerio. The sensitivity analysis of the tumor at the same time took only
four days and showed a good correlation with the results of patient treatment.