Cancer research: What’s exciting the experts?

Dr. Collin Vu, a medical oncologist and hematologist at the MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA, describes the current state of play in cancer research.

He also discusses a cancer therapy that he believes shows real promise.

The state of play and CAR-T cell therapy:
“Over the past 1–2 decades, we have seen different methods of treating cancer that are starkly different from the chemotherapy of old. And in a short time interval, [these] have gone from experimental to standard-of-care relatively quickly,” said Dr. Vu.

He explained how traditional chemotherapy destroys cancerous and healthy cells indiscriminately, which causes significant side effects. Dr. Vu continued:

“Starting around the turn of the century, ‘targeted’ agents that focused on treating a specific abnormality found inside cancer cells changed the landscape for treatment of certain cancers, including blood cancers like chronic myelogenous leukemia and lung cancers.”

In some cases, he explained, cancers that had almost always been fatal became treatable chronic conditions.

Since then, treatments have continued to improve and, in 2014, “The era of immunotherapy began, with the approval of several drugs that affected the activation of a patient’s immune system to fight cancer, changing drastically the survivability of the devastating diagnosis of metastatic melanoma.”

Dr. Vu is particularly excited about chimeric antigen receptor technology (CAR-T) cell therapy. He explained to MNT:

“The procedure consists of taking a patient’s own immune cells — T-cells — and engineering them to recognize a specific cancer target. Once infused back into the body, these cells recognize the specific cancer cell and destroy it.”

The first CAR-T cell therapy was approved in 2017. But since then, regulators have only approved a handful of these therapies for blood cancers.

There are still challenges to overcome, but Dr. Vu believes that CAR-T cell therapy shows significant promise.

“Currently ongoing, there are hundreds of registered clinical trials using CAR-T. Over the next years and decades, as these trials enroll and complete, we will be able to fully realize the potential for this new method of therapy,” he said.

“Although we have not yet been able to shed completely our reliance on treatment with standard chemotherapy, the development of these newer methods of killing cancer has opened and will continue to expand the ability to treat and give hope to patients who, in the past, would have had very few options for treatment and a dismal prognosis.”

Surgical vision and artificial intelligence
Dr. Stamatia Giannarou is excited about the future of cancer surgery. “With recent advances in medical imaging and surgical robotics, cancer surgery is entering a new era that is set to bring major benefits to healthcare and society more widely.”

Dr. Giannarou is a Royal Society University research fellow and a lecturer in surgical cancer technology and imaging at the Hamlyn Centre for Robotic Surgery, at Imperial College London (ICL), in the United Kingdom.

“The main goal of cancer surgery is to remove all of the cancerous tissue while sparing as much healthy tissue as possible,” she explained. “In practice, this is often a formidable challenge for surgeons.”

“Surgery on brain tumors is particularly demanding, and the outlook for people with such tumors remains very poor. Brain tumors kill more children and adults under the age of 40 than any other cancer, and fewer than 1 in 5 survive 5 years after being diagnosed,” she explained.

“My research aims to develop a navigation platform that highlights cancer tissue in real time in the operating theater, guiding the surgeon’s decisions and therefore making the surgery more precise and personalized to each patient.”

Dr. Giannarou believes that this “has the potential to drastically advance the outcome and safety of brain tumor surgery and could also transform surgery for other cancers, too. Using such a technique is hugely exciting because it will improve people’s quality of life and life expectancy, with obvious huge impacts on society and the economy.”

Cancer is caused by a buildup of mutations in DNA. Prof. Rudolf Aebersold, from the Institute of Molecular Systems Biology, at ETH Zurich, in Switzerland, is trying to understand what these mutations mean for a cell.

“In recent years, advanced DNA sequencing technologies applied to cancer tissue samples have identified large numbers of disease-associated genomic mutations.”

Despite this growing insight, as Prof. Aebersold told us, “Limited progress has been achieved toward understanding how and to what extent genomic mutations affect and eventually perturb biochemical and cellular functions, thus causing the disease.”

In other words, we are becoming good at identifying what part of the genetic message is at fault, but it is difficult to know what the effects of these DNA changes are.

“Myself and [Dr.] Martin Mehnert developed a methodological framework that allows us to directly measure the consequences of disease-associated mutations on the proteome at several levels,” he continued.

Genes code for proteins, and the proteome Trusted Sourceis the full set of proteins that a given genome can produce.

Their framework “consists of a suite of mass spectrometric techniques that detect alterations in the structure of the mutated protein state of its interaction network composition of the entire cellular proteome and phosphoproteome”
When a phosphate group is added to a protein, it changes the protein’s behavior. Phosphoproteomics is a way of identifying which proteins have been phosphorylated. This gives clues about each protein’s activity levels.

Combining this information, as Prof. Aebersold told MNT, indicates “the effects of disease-associated mutations on the functional state of the cell at unprecedented resolution.”

Recently, Prof. Aebersold and colleagues have focused on an enzyme called DYRK2, which is linked with “different cancer types and associates with other proteins in a functional complex.” This protein acted as a model to test their framework.

“We foundTrusted Source that different mutations of DYRK2 created distinct but different proteomic signatures. For example, a single point mutation was shown to be sufficient to disrupt protein interactions, ultimately leading to the disassembly of entire protein complexes. Other mutations directly interfered with the activity of the kinase affecting the phosphorylation of known cancer driver proteins.”

Overall, Prof. Aebersold believes that their “work demonstrated that integrating different layers of proteomic information provides powerful insights into the functional consequences of genomic mutations on a broad scale and their translation into cancer phenotypes.”

Although this work will not directly benefit patients for some time, he explained that it “fills an essential knowledge gap between cancer-associated genomic variants and the altered cellular functions that cause the disease.”

Microrobots swimming upstream on sound waves
“Nanotechnology is regarded as one of the most promising tools for cancer treatment, but nanotherapeutics have suffered from poor efficacy to date,” wrote Dr. Daniel Ahmed, assistant professor of acoustic robotics for life sciences and healthcare at ETH Zürich.

“A major hurdle is that nanodrugs rarely reach the site of the tumor. The vasculature of a tumor,” he explained, “is often dilated, follows a tortuous route, and contains pores. Within this leaky vasculature, blood flow decreases significantly.”

Because of these factors, blood flow alone is not sufficient to transport nanodrugs throughout the tumor.

One potential solution might be to “steer” these drugs using robots. “However, the application of micro- and nanorobotsTrusted Source in the vasculature system where robots need to be controlled within an imposed blood flow is extremely challenging,” Dr. Ahmed noted.

Tiny robots are no match for the might of a functioning circulatory system, literally pulsing with life. However, Dr. Ahmed believes that there is a way to create robots that can “propel against the flow,” which would ignite a “paradigm shift in targeted drug delivery in medicine.”

“Inspired by many naturally occurring microswimmers, such as bacteria and spermatozoa, that exploit the nonslip boundary conditions of the wall, we reportTrusted Source on the design and characterization of self-assembled microswarms that can execute upstream motion triggered by a combination of external acoustic and magnetic fields.”

These “external field-induced robots” do not require an onboard power supply or intricate moving parts, which means that they can be scaled down to nanometer-size. “We demonstrated microrobot motion against a flow of 1.3 millimeters per second, which is similar to that present in tumor vasculature,” Dr. Ahmed reported.

Although more work is needed, Dr. Ahmed explained, “The developed process is a step closer to delivering cancer drugs locally and a pivotal advancement with key clinical implications.”