Dr. Gail Darling
Dr. Gail Darling, a thoracic surgeon in UHN's Sprott Department of Surgery and the Kress Family Chair in Esophageal Cancer at UHN, grows organoids with cancerous tissue from patients to determine the best treatment. (Photo: Tim Fraser)

People around the world are diagnosed with esophageal cancer every day, all of whom can only hope the therapy they receive will work. But what if instead of simply hoping a treatment is effective, you could know for sure that what your physicians are doing is designed to target your specific illness?

It's these kinds of highly personalized treatments that UHN researchers are working toward with organoids, a groundbreaking technology that allows researchers to grow small versions of an organ – sort of an "avatar" of your tumour.

They're creating a representation of a patient's specific esophageal cancer tumours and then using these organoids in a lab to test the effectiveness of different treatments without risking harm to patients.

This kind of world-leading research couldn't come at a better time: esophageal cancer remains one of the most lethal cancers, with just 15 per cent of Canadians diagnosed with the disease surviving beyond five years.

It also couldn't happen anywhere else. UHN has an esophageal disease program that's entirely focused on this cancer, while its multidisciplinary approach to care means that clinicians and researchers are always working together to come up with novel solutions to hard-to-solve problems.

Today, surgeons, radiation oncologists, medical oncologists and more collaborate not just on research but to minimize patient visits and provide expert patient care.

"Previously we worked in silos, now we work together to improve delivery of care and optimize treatment," says Dr. Gail Darling, a thoracic surgeon in UHN's Sprott Department of Surgery and the Kress Family Chair in Esophageal Cancer at UHN. "Our program's clinical oncologists and pathologists are entirely focused on esophageal cancer.

"It's not grouped with other GI cancers, and that's what makes the difference."

Dr. Jonathan Yeung
Dr. Jonathan Yeung, a thoracic surgeon in UHN's Sprott Department of Surgery, who leads the translational component of the Esophageal Cancer Program, is using organoids to better understand why esophageal cancer recurs frequently. (Photo: Tim Fraser)

So far, that teamwork has paid off with an operative mortality rate that's the lowest in the province and well below the world benchmark.

But more work needs to be done, says Dr. Darling. One big challenge is that every patient's response to treatment remains unpredictable, making esophageal cancer difficult to treat.

"There is no way to know what works," she explains. "Unlike other cancers, there are no common gene mutations to target for esophageal cancer, so what works for one patient may not work for another."

That's why this organoid research is so exciting. To create these tumours – which they have successfully done – her team puts cancerous tissue from patients into dishes where hundreds of organoids can grow over a few weeks' time. Because the tiny spherical cultures truly represent their originating tumours, they can be used to see what cancer treatments actually work.

"The holy grail of cancer treatment is to treat cancers based on their specific biology," says Dr. Jonathan Yeung, a thoracic surgeon in UHN's Sprott Department of Surgery, who leads the translational component of the Esophageal Cancer Program. By treating patient-specific organoids with a battery of cancer drugs available on the market, researchers can determine what works for each patient.

"We can provide a targeted second, third or even fourth line of therapy," Dr. Yeung says.

Researchers can use organoids to track the evolution of a tumour – taking samples before and after chemotherapy as well as post-surgery. If changes occur in the organoids, they can look for similar mutations in patients.

"This can help with personalized surveillance," explains Dr. Yeung, which is critical because the recurrence rate is high. "Esophageal cancer spreads easily, and it often comes back elsewhere."

Organoids
Organoids are small versions of an organ grown by researchers, thanks to leading-edge technology. (Photo: UHN)

Bolstering its personalization efforts is Molecular Characterization of Esophageal Adenocarcinoma (MOCHA), the team's cancer genome sequencing project. With MOCHA, researchers use a laser to isolate the cells of the cancer. They can then sequence the cancer's genome to learn more about it and predict whether existing drugs might be useful and what still-to-be-developed medications could one day be used to treat it.

"This will help us better understand why esophageal cancer comes back and how chemotherapy changes it," says Dr. Yeung.

The genome information is also included in its clinical database, which houses information on more than 800 patients, including such data as how many lymph nodes were removed during surgery to quality of life post-surgery.

"Data is key," notes Dr. Darling. "We have very granular clinical data that correlates with lab data so that we can carefully evaluate and refine our techniques, and strive to always improve."

This research, which has been solely supported by donors, shows the potential for personalized care across all types of diseases, says Dr. Yeung.

"We can use esophageal cancer as the model, but this paradigm can be adapted to other areas," he explains. "In the future, we won't be treating lung cancer or prostate cancer, we'll be treating Fred's cancer or Sally's cancer.

"We want to move away from inexact treatment to targeted care."

Read more stories in the new Sprott Department of Surgery magazine


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