Cell Research: Customize personalized medicine by measuring cancer cells

Researchers at the Massachusetts Institute of Technology (MIT) and the Dana-Farber Cancer Institute have developed a new method to determine whether an individual patient will respond to a specific cancer drug

This new technology involves taking tumor cells from a patient, treating the cells with drugs, and then measuring changes in cell quality, which can be applied to various cancers and drug treatments, Scott Manalis said

Manalis said: "Basically all anti-cancer drugs used clinically directly or indirectly prevent the growth of cancer cells

This new research focuses on malignant glioma (a malignant brain cancer) and is part of a collaboration between the Koch Institute and the Dana-Farber Precision Medicine project to find New biomarkers and cancer diagnostic tests

Manalis and Keith Ligon, associate professor of Harvard Medical School and director of the Dana-Farber Patient Derivative Model Center, are the senior authors of the study, which was published in today's Cell Report

Measure tumor cells

Approximately 13,000 Americans are diagnosed with glioblastoma each year.

"For this disease, you don't have much time to make adjustments

Patients diagnosed with glioblastoma usually take a chemotherapy drug called temozolomide (TMZ)

Currently, doctors can use a genetic marker-MGMT gene methylation-to predict whether a patient will respond to TMZ treatment

In recent years, Manalis and Ligon have been working on a new method of predicting patient response based on measuring the response of tumor cells to treatment rather than genomic characteristics

"The idea behind functional precision medicine is that for cancer, you can take out the patient's tumor cells, give them the drugs that the patient may get, and predict what will happen before giving them to the patient

Scientists are studying many different methods to achieve functional precision medicine.

A few years ago, Manalis, Ligon and their colleagues demonstrated that they can use this technology to analyze the response of two types of cancer, glioblastoma and acute lymphoblastic leukemia

Using the high-throughput version of the system they developed in 2016, they can calculate the precise MAR using only 100 cells per patient

In their new study, the researchers decided to see if a simpler and significantly faster method-measuring subtle changes in the mass distribution of single cells between drug-treated and untreated cancer cells-could predict patient survival

They found that by simply measuring the quality difference between the cells before and after treatment, using only 2,000 cells per patient sample, they can accurately predict whether the patient will respond to TMZ

Better forecast

The researchers showed that their measurement results are as accurate as MGMT methylation markers, but the measurement has an additional advantage that it can work in patients whose genetic markers cannot reveal TMZ susceptibility
.
For many other types of cancer, there are no biomarkers that can be used to predict drug response
.

"Most cancers simply don't have genomic markers
that can be used .
We believe that this functional approach can work in the absence of any genomic marker selection," Manalis said
.

Because this test is performed by measuring changes in quality, it can be used to observe the effects of many different types of anticancer drugs, regardless of their mechanism of action
.
TMZ works by stopping the cell cycle, which causes cells to grow larger because they can no longer divide, but their mass still increases
.
Other anti-cancer drugs work by interfering with cell metabolism or destroying its structure, which also affects cell quality
.

The long-term hope of the researchers is that this method can be used to test several different drugs on the cells of a single patient to predict which treatment is most effective for that patient
.

"Ideally, we would test the drugs that patients are most likely to get, but we would also test alternatives: Ligan also served as director of neuropathology at Brigham and Women’s Hospital and a pathology consultant at Boston Children’s Hospital
.

Manalis and Ligon co-founded a company called Travera.
The company has obtained a license for this technology and is currently collecting data from samples of several different types of cancer patients, hoping to develop clinically validated laboratory tests.
Used to help patients
.

DOI

10.
1016/j.
celrep.
2021.
109788

Article title

Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models