Cancer and Dementia Have Factors in Common, so Why Study Them Separately?

For any biomedical scientist, the acid test is whether their laboratory research makes a real difference to people. Will promising anticancer results in models and experiments, for example, become new therapies to extend and save lives?

When the Japanese pharmaceutical company Eisai realized that its traditional approach to discovery was not fully representing the way diseases present in patients, it decided to change its drug discovery strategy. The company wanted to be sure it could reflect many of the systemic conditions that different people might develop. And so Eisai reorganized its research approach to emphasize how seemingly disparate diseases can start in similar ways—and how this manifests in patients.

In doing so, it swept away barriers that previously separated its oncology and neurology research groups. The move has encouraged its scientists with diverse backgrounds and expertise to communicate and collaborate. “This situation seems to refresh their scientific insights,” says Takashi Owa, chief discovery officer and president, Deep Human Biology Learning, Eisai Co., Ltd. “Our scientists are freer to allow the science to guide them to novel potential therapies.”

Eisai calls its new approach Deep Human Biology Learning (DHBL). It builds on the emerging realization that different diseases can have common roots and causes. Collapse of protein regulation, for example, can trigger many different medical problems, from dementia to cancer. That is, the same process—the accumulation of misfolded and unfolded proteins—triggers different disease pathways depending on the cells in which it occurs.

According to Toshimitsu Uenaka, PhD, president of Eisai’s Epochal Precision Anti-Cancer Therapeutics (EPAT) division, located in Exton, Pennsylvania, the DHBL approach has so far focused on making clinically relevant experimental models that more closely resemble the real diseases.

Clinical relevance was a problem under the previous structure. “In cancer research, we found that preclinical findings were not as relevant as we had hoped,” Uenaka says. “Unexpected outcomes, both in efficacy and safety, sometimes happened in the clinic.”

Under the new DHBL structure, the company now takes what Uenaka calls a “bedside-to-bench” approach. “We have focused on clinical biomarker research by using patient specimens from our clinical trials and have found several hints about what is happening in patients,” he says. “We will make use of this information in our future drug discovery to advance the development of novel treatments.”

Protein biology for cancer

EPAT is one of Eisai’s discovery centers, and its particular focus is on the role of protein biology in cancer. Specifically, the EPAT team researches how protein-related processes affect gynecologic cancers and breast cancers, as well as specific types of malignant cancers, including pancreatic cancer, triple-negative breast cancer and scirrhous gastric cancer.

The DHBL approach of looking for common roots and causes should help with cancer research, Owa says. The company is focusing on the early stages of the disease, because early-stage tumors tend to be homogenous, with a limited number of relevant gene mutations. Targeting these genes and associated pathways in early-stage patients could offer a potential cure or even prevent the cancer taking hold in the first place, he says—a strategy that would be less effective as the disease progresses and spreads. “To continue to be successful, it is critical for us to enrich the project pipeline in the early stage of oncology research and development,” he says.

Eisai’s enrichment focuses on three areas. The first is the identification of new ways to prevent cancer from developing resistance to existing drugs. The company is working with a selective inhibitor it believes can block a key protein-protein interaction in the signaling pathway called Wnt, which is closely associated with cancer.

The second focus is on molecular techniques to selectively target and degrade the proteins in ‘molecular glue’ that cancers need to proliferate, says Owa. These methods could be particularly useful against those cancers that are less sensitive to immunotherapies.

The third focus is on antibody-drug conjugates (ADCs), which can be designed to deliver specific anti-cancer molecules to the heart of the tumor, avoiding surrounding healthy tissue. “ADCs may allow us to deliver an anticancer payload to cancer cells in a selective manner,” says Owa. 

Strong connections

EPAT is working on a novel ADC to deliver anticancer agents to multiple tumor types. Central to that work are methods the company has developed to link the agent to specific antibodies. Called Residue-Specific Conjugation Technology (RESPECT®), the techniques are designed to reduce variability in the manufacturing process and so improve the quality of the therapeutic molecules.

Improving the linkage in an ADC means it is more likely to get the anticancer therapy to the desired impact area of the tumor and release the medicine directly into it, minimizing the impact on surrounding healthy tissue.

“We are now trying to show in clinical trials whether our ADC has anti-tumor efficacy and if it can improve the microenvironment around the tumor,” Uenaka says. Eisai has several anticancer chemicals that could be linked to antibodies. “And genetics from our data science show what we should be targeting,” he adds.

DHBL might be a big change, but Eisai believes it will pay off. Owa sees rapid shifts in the oncology research landscape, as companies bet on the next big thing. “People are starting to ask what the next game changer following cancer immunotherapy will be,” he says. And for Eisai, the logical approach is to follow the biology.

Click here to learn more about Eisai’s new biology-first approach to cancer research