Cancer Cell: Imaging technology predicts cancer drug resistance

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Cancer Cell: Imaging technology predicts cancer drug resistance

Cancer Cell: Imaging technology predicts cancer drug resistance.

In a recent study, researchers at the University of Cambridge show that imaging techniques can replace the need for invasive tissue biopsies to help quickly determine whether cancer treatments are effective.

In a study published in the journal Cancer Cell, researchers from Cancer Research UK’s (CRUK) Cambridge Institute show how to use a new technique called hyperpolarization (which involves efficient operation in strong magnetic fields) geomagnetic molecules) to monitor the effectiveness of drugs in slowing the growth of cancer cells.

In healthy tissue, cell proliferation is a tightly controlled process. When this process goes awry, the cell cycle can be disrupted, leading to uncontrolled growth and tumor development.

However, the growth and maintenance of all tissues requires “energy”, and our cells break down glucose and other sugars to produce pyruvate, which is then converted into lactate. This is important for generating energy.

Tumors metabolize differently than healthy cells and generally produce more lactate. This metabolic pathway is influenced by a protein called FOXM1, which controls the production of metabolic enzymes that convert pyruvate into lactate. FOXM1 also controls the production of many other proteins involved in cell growth and proliferation.

About 70 percent of all breast cancer cases are of a type called estrogen receptor (ER) positive. In many cases of ER-positive breast cancer, an enzyme called PI3Ka is activated. This leads to the abundance of FOXM1, which allows cancer cells to grow uncontrollably, which is characteristic of tumor cells.

Drugs that inhibit PI3Ka are currently being tested in breast cancer patients. This class of drugs should be able to reduce the amount of FOXM1 and check tumor growth. However, a patient’s tumor may be innately resistant to PI3Ka inhibitors, or may acquire resistance over time, making the drug less and less effective.

Lead author Dr Susana Ros, from the CRUK Cambridge Institute, said: “Due to advances in cancer treatment, our medicines are becoming more and more targeted, but not all medicines work in every situation – some Tumors are resistant to specific drugs. What we need are biomarkers that can tell us whether the drug is working.”

The researchers took breast cancer cells from patients and grew them in “avatars” in mice to make them They were able to study tumors in detail. They found that in tumors resistant to PI3Ka inhibitors, cancer cells continued to produce FOXM1, implying that the molecule could be used as a biomarker of drug resistance in patients with ER-positive breast cancer.

Invasive tissue biopsy is usually required to check whether the tumor continues to produce FOXM1 and thus whether the PI3Ka inhibitor is still working. However, researchers have used a new imaging technique to monitor it non-invasively in real time.

The technique the team developed and used is called hyperpolarization. First, the team produced a special kind of pyruvate with heavier than normal carbon atoms (they carry an extra neutron, hence the name carbon 13 molecule).

The researchers then “hyperpolarized” the carbon-13 pyruvate by cooling it to about 1 degree above absolute zero (-272°C) and exposing it to extremely strong magnetic fields and microwave radiation. magnetization. The frozen material is then thawed and dissolved in the injectable solution.

The patient is injected with the solution and then undergoes a routine MRI scan. The hyperpolarized carbon-13 pyruvate molecules had a signal 10,000 times stronger than that of normal pyruvate, making these molecules visible when scanned. The researchers could use the scan to see how quickly pyruvate was being converted to lactate—a condition that only persisted in the presence of FOXM1, suggesting the drugs were not working properly.

“By using this new imaging technique in a breast cancer model, we have been able to detect the presence of the biomarker FOXM1 to look for a surrogate, the rate at which pyruvate is converted to lactate,” added Dr. Ross.

Reference:

Susana Ros et al, Metabolic Imaging Detects Resistance to PI3Kα Inhibition Mediated by Persistent FOXM1 Expression in ER+ Breast Cancer, Cancer Cell (2020). DOI: 10.1016/j.ccell.2020.08.016

Cancer Cell: Imaging technology predicts cancer drug resistance

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