Tel Aviv
University Scientists Rein in Lingering Cancer Cells
By Judy Siegel-Itzkovich June 27, 2018 , 1:05 pm
And give worship to
the Lord your God, who will send his blessing on your bread and on your water;
and I will take all disease away from among you. Exodus 23:25 (The Israel
Bible™)
Illustration of image-guided surgery using probes that
light up in the presence of cancerous cells. (Credit: TAU)
Many cancer patients die not from the localized malignant
tumor that is removed in surgery but when lingering cancer cells from the tumor
spread by metastasis. Now, a team of researchers headed by Prof. Ronit
Satchi-Fainaro of the physiology and pharmacology department of at Tel Aviv
University’s Sackler Faculty of Medicine believe they have found a way to rein
in these bandit cells that could dramatically improve the chances for patients
after surgery.
They developed a fluorescent tag of injected polymers
that is activated by an enzyme of which the cancer cells produce too much. This
smart “Turn-ON” probe for guided imaging surgery is injected into the oncology
patient a few hours before an operation to remove the primary tumor. The tag
helps the surgeons pinpoint exactly where the cancer – even just a few cells
that can’t be identified with an magnetic resonance imaging (MRI) or
computerized tomography (CT) scanner – is located. The doctors then can try to
remove more cancer cells than was ever possible before.
“In cases of melanoma [the most dangerous skin cancer]
and breast cancer, for example, surgeons may think they have removed everything
and that the
patient is cancer free. But even if only a few cells remain after surgery, the cancer may recur and spread,” said Satchi-Fainaro, who is president of the Israeli chapter of the Controlled Release Society and co-editor-in-chief of the journal Clinical Cancer Drugs. “Our new technology can guide the surgeon to
completely excise the cancer.”
patient is cancer free. But even if only a few cells remain after surgery, the cancer may recur and spread,” said Satchi-Fainaro, who is president of the Israeli chapter of the Controlled Release Society and co-editor-in-chief of the journal Clinical Cancer Drugs. “Our new technology can guide the surgeon to
completely excise the cancer.”
The team, which included lab students Rachel Blau, Yana
Epshtein and Evgeni Pisarevsky, has just published the discovery in the journal
Theranostics .
“When the cyanine molecules are held together by the
polymer particle, the light waves they emit cancel each other out, and they
remain dark,” said Sachi-Fainaru. “But once the nanoparticle reaches a cancerous
cell, the connecting polymer is cut. The cyanine molecules move away from each
other and shine brightly, but in the surrounding healthy tissue the polymer is
not cut, and the area remains dark. Cathepsin cuts the tag from the polymer and
turns on its fluorescence at a near-infrared light, guiding the surgeon in real
time while taking out the solid tumor so he or she can also avoid cutting out
any “non-glowing” healthy tissue.
The TAU technique makes use of near-infrared technology to find proliferating cancer cells. “The probe is a polymer that connects to a fluorescent tag made of molecules of cyanine dye using a ‘linker,’ which is recognized by an enzyme called cathepsin. This substance is overproduced in many cancer types,” she explained.
The TAU technique makes use of near-infrared technology to find proliferating cancer cells. “The probe is a polymer that connects to a fluorescent tag made of molecules of cyanine dye using a ‘linker,’ which is recognized by an enzyme called cathepsin. This substance is overproduced in many cancer types,” she explained.
In professional terms, it means that the smart sensor has
high sensitivity (it detects all the cancer cells) and also high selectivity
(it does not tag healthy cells). In this way, the surgeon identifies the
location of the cancer cells in real time, that is, during the surgery itself.
Existing imaging device cannot do this.
The scientists first examined the effect of the probe in
the lab on healthy skin and mammary tissue, followed by melanoma and breast
cancer cells. They then used mouse models of melanoma and breast cancer to
perform routine tumor-removal surgeries and smart probe-guided surgeries.
“The mice that had regular surgery experienced recurrence
and metastasis much sooner and more often than those that underwent our smart
probe-guided surgery,” noted Satchi-Fainaro. “Most importantly, those which
experienced the smart-probe surgery survived much longer.”
Prof. Ronit Satchi-Fainaro, chair of the Dept. of
Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine. (Credit:
Times of Israel Screenshot/Jonathan Bloom)
The results were very promising: mice analyzed without
the sensor were soon diagnosed with metastasis or recurrence of the tumors
themselves, and their life expectancy was short; only 40% of the mice in this
group survived 120 days after the operation. But when the operation was
performed using the new sensor, 80% of them remained healthy after 120 days.
Thus, 60% of the mice analyzed the conventional way eventually died from the
disease, compared to only 20% of those analyzed using the smart sensor.
The TAU scientist added that the probe may also cut the
need for repeated surgeries in patients with cancer cells that remain in the
edges of removed tissue. “Altogether, this can lead to the improvement of
patient survival rates. We are currently designing and developing additional
unique polymeric ‘Turn-ON’ probes for using in image-guided surgery. We
are always looking for ways to improve sensitivity and selectivity, which are
paramount to cancer patients’ care,” she concluded.
“We have registered several patents, concluded
Sachi-Fainaru, “and now we are negotiating with a number of pharmaceutical
companies to advance to clinical trials and later to commercial production that
can significantly increase patients’ chances of surviving the disease.”
