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Scientific Stunt Double: How a Molecular Twin Is Changing Cancer Treatment, Research

When advanced technology and data from patients’ individual cells join forces, they can enormously expand what we know about cancer and how to treat it.

Cedars-Sinai developed its Molecular Twin Precision Oncology Platform in part to create cancer treatment plans tailored to an individual patient’s biology. It’s dubbed “Molecular Twin” because it uses AI to create virtual replicas—a sort of scientific stunt double—of patients’ cancers and other characteristics. The platform uses AI, as well, to analyze the cancer’s DNA, RNA, protein markup and other molecular details.

The technology also is aiding researchers in their work to discover new treatment targets and uncover important new biomarkers (biological molecules that are signs of disease). These findings eventually may be used to battle cancer in the population at large.

Here are four ways the Molecular Twin technology is aiding Cedars-Sinai Cancer investigators.

"We have a platform built on molecular testing and AI. That’s a perfect crossroads for what we’re doing in the lab."

Examining Exceptional Responders With Pancreatic Cancer

In about 1% of people with pancreatic cancer, the available treatments are extremely effective in wiping out cancer. This group is known as “exceptional responders.” Something about their genes, immune system or microbiome (the collection of tiny organisms that live in and on our bodies) makes their cancer very treatable.

What if we could identify why their response is so strong and then use that knowledge to spread this power to other patients? That’s a challenge Arsen Osipov, MD, program lead of the Pancreatic Cancer Multidisciplinary Clinic and Precision Medicine Program, has confronted.

"We have a platform built on molecular testing and AI," he said. "That’s a perfect crossroads for what we’re doing in the lab."

He’s expanding his research—and the platform—by adding in analysis of the tumor microenvironment. This is the area around cancer cells that has been transformed by the cancer, often making it more hospitable to the malignant cells than healthy ones.

"Many scientists and clinicians believe that one reason why some patients are exceptional responders is that they have something unique about how their immune system interacts with the tumor microenvironment," Osipov said.

His current study will use the platform to reexamine data from 74 patients who were part of the first Molecular Twin study published by Cedars-Sinai, this time taking into account their tumor microenvironment.

An additional 50 patients who are exceptional responders will also be added.

Read: Cedars-Sinai Develops New Tools to Improve Pancreatic Cancer Patient Care


Staying a Step Ahead of Lung Cancer

Oral medications that target specific types of cancer cells were a game-changing breakthrough for certain lung cancers, including a molecular alteration called an EGRF mutation. The therapies often help patients with everything from early-stage cancers to those that have spread to other parts of the body.

However, at some point in many cases, the medication stops working and the tumor cells start to grow again.

"It’s what we call resistance—the tumor cells get smart and understand how to keep growing despite the treatments we’ve been using," said Karen Reckamp, MD, director of Medical Oncology and associate director for clinical research for Cedars-Sinai Cancer.

Using the Molecular Twin platform, Reckamp and her colleagues are studying different aspects of the blood, searching for markers that could alert them to resistance. By finding these markers and unraveling why resistance occurs, doctors could better predict who might develop resistance or when it will happen and then change therapies before resistance occurs.

"In some cases, if someone doesn’t have any markers in the blood, we might even consider decreasing the therapy,” Reckamp said. "We really want to personalize that therapy.

Read: The New Lung Cancer Landscape


Tracing Biomarkers for Colorectal Cancer

Colorectal cancer is the second most common cause of cancer death in the United States, according to the American Cancer Society (ACS). It’s the leading cause of cancer death in men under 50, ACS reports.

"Colorectal cancer is occurring more often than expected in people at the prime of their lives,” said Jane Figueiredo, PhD, director of Community and Population Health Research. “We cannot take years to understand why this is happening.”

Figueiredo and her colleagues are working to identify biomarkers in the blood that would indicate who is at greatest risk of dying of colorectal cancer or developing advanced disease. The study includes data and tissue samples from more than 1,000 cancer patients. Using machine-learning techniques, the team will analyze the blood on multiple fronts, including genetics, proteins and metabolic factors.

Read: The New Lung Cancer Landscape


Targeting an Area of Great Need in Breast Cancer

When breast cancer spreads to other sites in the body, it ultimately metastasizes to the liver in about half of patients. Breast cancer that spreads to the liver is especially difficult to treat—the liver frequently becomes resistant to treatment and is a leading cause of advanced breast cancer death, said Jin Sun Bitar, MD, an assistant professor of Medicine at Cedars-Sinai Cancer.

"We need better understanding of the biology behind the liver metastasis to develop targeted treatments," Bitar said. "Our study could provide a foundation for finding novel treatments to help this population."

Bitar is leading an effort to create a bank of tissue samples donated by breast cancer patients who had liver biopsies. She and her team will analyze the unique tumor biology of these metastases using the Molecular Twin platform. They will compare breast tumor tissue with the metastatic tissue. Their work will also examine the role of antibodies and the immune system in the liver.

Read: How Do Your Genes Fit? Cracking the Code on Breast Cancer Risk


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