Cornell Researchers Have Discovered Precision Medicine Treatment That Overcomes Chemotherapy-Resistant Gastric Cancer

New application of an already-established leukemia drug may offer personalized treatments for other hard-to-treat cancers as well

Researchers at Weill Cornell Medicine have discovered a protein that can cause resistance to an otherwise effective form of gastric cancer treatment. Not only did this research result in the discovery of a new precision medicine target for further study, it showed that a common cancer drug used for other forms of cancer can be applied to individuals who have variations of this protein. 

The study’s findings may provide hospitals and oncology leaders with a new personalized treatment option for patients with gastric and other cancers.

Manish Shah, MD, Director of the Gastrointestinal Oncology Program and Chief of the Solid Tumor Oncology Service in the Division of Hematology and Medical Oncology at Weill Cornell Medicine
“Most patients with gastric cancer live less than a year, and if we could figure out a way to make the taxanes more effective, we could have a bigger impact on patients,” said study co-senior author Manish Shah, MD (above), in a Weill Cornell Medicine news release. According to Shah, about 80% of gastric cancer patients develop taxane-resistant tumors, significantly affecting their chances of survival. (Photo: New York Presbyterian.)

According to a Weill Cornell Medicine news release, this study “combined clinical insight, laboratory experiments and sophisticated computational analysis to determine how some tumor cells resist a family of chemotherapy drugs called taxanes. Taxane treatment works by interfering with proteins that make up the cell’s internal skeleton, but the variant protein, called CLIP-170S, allows cancer cells to dodge that interference.” 

The researchers published their findings in the journal Developmental Cell, titled, “CLIP-170S Is a Microtubule +TIP Variant That Confers Resistance to Taxanes by Impairing Drug-Target Engagement.”

Rise of Cancer Resistance

Taxanes are a class of chemotherapeutic compounds often used as a first-line treatment option for certain cancers. While an effective treatment, taxane-resistant cancer cells can arise, narrowing the number of options available to patients and worsening their overall prognosis, according to the news release.

The multidisciplinary researcher team at Weill Cornell Medicine believe they discovered how taxane resistant cancer cells develop. The scientists used a combination of clinical insights, laboratory experimentation, and computational analysis to identify a previously unrecognized protein variation that affects how cancer cells respond to taxanes. 

“Starting with a database of approved drugs, we created a computational program that was able to screen through these molecules, in silico, to identify the ones that would essentially make resistant cells look more like cells that are sensitive to taxanes,” said co-senior author Olivier Elemento, PhD, Director of the Englander Institute for Precision Medicine (EIPM).

“We identified a novel variant that is clinically prevalent and is expressed in more than 60% of patients with gastric cancer and operates with a mechanism that’s different from previously discovered ones,” explained co-senior author Paraskevi Giannakakou, PhD. Giannakakou is a professor of pharmacology in medicine and director of research in the Division of Hematology and Medical Oncology, and associate director for education in the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

Promise of Future Precision Medicine Therapeutics

This finding has provided researchers with a promising new protein variant that can be genetically tested for and targeted with future treatment methods. “Everyone tries to understand mechanisms of taxane resistance, and yet nothing is helping patients clinically, none of the resistance mechanisms identified in the lab have made a clinical impact,” Giannakakou said.

Equally as important as the potential for new therapeutics, however, was a finding by the team that an existing leukemia drug—Imatinib (marketed by Novartis under the brand names Gleevec and Glivec)—was highlighted by their analysis as a potential candidate for treating taxane-resistant gastric cancer cells. While imatinib is used for some types of cancer, it is not currently used in treating gastric cancer. 

Researchers conducted follow-up research that experimentally demonstrated imatinib effectiveness against taxane-resistant gastric cancer cells, offering the potential that this already-approved medication can be used to improve the outcomes of patients with gastric cancer. 

“That’s important, because it demonstrates how you can go in without preconceptions and use computational screening to come up with molecules that have an effect,” Elemento explained. 

Hospital and oncology leaders will want to follow this research as it continues, especially because potentially implementable clinical improvements to care are already available using imatinib. This new discovery, while immediately impactful to gastric cancer patients, also opens the door to overcoming taxane resistance in other cancers, potentially offering new precision medicine treatments for many types of cancers in the future. 

—Caleb Williams

Related Information:

Protein Variant Identified That Renders Chemotherapy Ineffective in Gastric Cancer

CLIP-170S Is a Microtubule +TIP Variant That Confers Resistance to Taxanes by Impairing Drug-Target Engagement

Manish Shah, MD

Olivier Elemento, PhD

Paraskevi Giannakakou, PhD

Interviews With Precision Medicine Movers