Researchers identify proteins receptive to treating ovarian cancer

Researchers at Northeastern University have identified two proteins abundant on drug-resistant ovarian cancer cells that become receptive to chemotherapy when treated with light.

Published in the journal Photochemistry and Photobiology, the research findings represent promising progress in the treatment of one of the most deadly forms of cancer. By targeting cancer cells with photosensitive antibodies and then shining light on them, researchers have made previously untreatable tumors receptive to drugs.

“The cells that are exposed to subtle doses of light, they accumulate some photo damage and become more susceptible to chemotherapy,” said Bryan Spring, associate professor of physics. “It’s a missing piece in oncology. Photomedicine is very complementary to chemo and immunotherapies.”

Spring’s co-investigators included Northeastern physics graduate students Sudip Timilsina and Anish Raju Amara and Rafay Abu, who is assistant director of Northeastern’s Mass Spectrometry Facility.

Photoimmunotherapy is an emerging cancer treatment that kills targeted cells and may then induce the body’s immune response to attack remaining cancer cells. But the approach has been used previously on cancer cell proteins that aren’t abundant in ovarian cancer.

Ovarian cancer cells are heterogeneous, Spring said, meaning they vary from patient to patient and even within a tumor. One of the goals of this research, he said, was to find some consistency among the cells that could serve as a target for treatment.

Using a technique called proteomics, researchers extracted the proteins from ovarian cancer cells and looked for promising photoimmunotherapy targets. The one they expected to find—which has been successful in clinical trials to treat other forms of cancer—didn’t show up consistently enough.

But a broader look revealed something different. Two proteins appeared on the cell surface of all patient samples.

“What we found so far is that for each patient there was a marker that would hit every single cancer cell,” Spring said.

Identifying new protein targets for light-activated cancer therapy means ovarian cancer patients can benefit from photoimmunotherapy, Spring said.

Ovarian cancer remains among the most deadly cancers, partly because it typically doesn’t produce symptoms until the disease is in advanced stages. But this discovery opens up potential treatment options that can be tailored to individual patients and may allow some to reduce reliance on the intense cycling of intravenous chemotherapy.

Targeting the proteins with a light-activated drug and then shining light will temporarily deplete the proteins, creating an entry for other treatment drugs and triggering the body’s immune system. Larger tumors, Spring said, can be especially difficult to treat.

Light-activated local therapy, he said, weakens the cells and creates a positive inflammation response, making it more likely that tumor cells beyond the treatment site will die because more tumor cells to the immune system.

“We want to do precision medicine where we find ways to look at each patient and tailor the treatment,” Spring says. “Otherwise, we’re just wasting resources, causing harm.”

Photoimmunotherapy also presents benefits before surgery. Tumor cells are “lit up” so they can be seen more clearly.

“If we prime surgical beds for follow-up chemo and immunotherapy, then you wouldn’t need as much of those drugs,” Spring said. “One of the goals of the research is to make life for a cancer patient more enjoyable. There’s so much suffering and the treatments are so grueling.”

This story is republished courtesy of Northeastern Global News news.northeastern.edu.

Researchers at Northeastern University have identified two proteins abundant on drug-resistant ovarian cancer cells that become receptive to chemotherapy when treated with light.

Published in the journal Photochemistry and Photobiology, the research findings represent promising progress in the treatment of one of the most deadly forms of cancer. By targeting cancer cells with photosensitive antibodies and then shining light on them, researchers have made previously untreatable tumors receptive to drugs.

“The cells that are exposed to subtle doses of light, they accumulate some photo damage and become more susceptible to chemotherapy,” said Bryan Spring, associate professor of physics. “It’s a missing piece in oncology. Photomedicine is very complementary to chemo and immunotherapies.”

Spring’s co-investigators included Northeastern physics graduate students Sudip Timilsina and Anish Raju Amara and Rafay Abu, who is assistant director of Northeastern’s Mass Spectrometry Facility.

Photoimmunotherapy is an emerging cancer treatment that kills targeted cells and may then induce the body’s immune response to attack remaining cancer cells. But the approach has been used previously on cancer cell proteins that aren’t abundant in ovarian cancer.

Ovarian cancer cells are heterogeneous, Spring said, meaning they vary from patient to patient and even within a tumor. One of the goals of this research, he said, was to find some consistency among the cells that could serve as a target for treatment.

Using a technique called proteomics, researchers extracted the proteins from ovarian cancer cells and looked for promising photoimmunotherapy targets. The one they expected to find—which has been successful in clinical trials to treat other forms of cancer—didn’t show up consistently enough.

But a broader look revealed something different. Two proteins appeared on the cell surface of all patient samples.

“What we found so far is that for each patient there was a marker that would hit every single cancer cell,” Spring said.

Identifying new protein targets for light-activated cancer therapy means ovarian cancer patients can benefit from photoimmunotherapy, Spring said.

Ovarian cancer remains among the most deadly cancers, partly because it typically doesn’t produce symptoms until the disease is in advanced stages. But this discovery opens up potential treatment options that can be tailored to individual patients and may allow some to reduce reliance on the intense cycling of intravenous chemotherapy.

Targeting the proteins with a light-activated drug and then shining light will temporarily deplete the proteins, creating an entry for other treatment drugs and triggering the body’s immune system. Larger tumors, Spring said, can be especially difficult to treat.

Light-activated local therapy, he said, weakens the cells and creates a positive inflammation response, making it more likely that tumor cells beyond the treatment site will die because more tumor cells to the immune system.

“We want to do precision medicine where we find ways to look at each patient and tailor the treatment,” Spring says. “Otherwise, we’re just wasting resources, causing harm.”

Photoimmunotherapy also presents benefits before surgery. Tumor cells are “lit up” so they can be seen more clearly.

“If we prime surgical beds for follow-up chemo and immunotherapy, then you wouldn’t need as much of those drugs,” Spring said. “One of the goals of the research is to make life for a cancer patient more enjoyable. There’s so much suffering and the treatments are so grueling.”

This story is republished courtesy of Northeastern Global News news.northeastern.edu.