Big Ideas

Weizhou Zhang, Ph.D.

An estimated 40% of women in the United States are obese, and an additional 30% are overweight. The obesity epidemic has led to the increased incidence of many chronic syndromes, such as diabetes, cardiovascular syndromes and cancer – including breast cancer. While cancer patients are treated based on available therapeutic regimens, special treatment to obese patients is lacking, which ultimately leaves many obese patients treated by a regimen that neither accords to their body weight nor maximizes their chances of surviving the disease.

Research reveals obese patients tend to have more complications than normal-weight patients during cancer treatment. Many new clinical trials are known to exclude obese cancer patients due to certain unpredictable complications arising from obesity. V Scholar Grant recipient Dr. Weizhou Zhang and his collaborators said they believe obese cancer patients should be treated with respect to their body mass index. Obesity has been shown to gravely increase the chances and progression of breast cancer, and Zhang said he believes there is a way to ensure obese patients receive equally effective treatment. Therefore, Zhang and his collaborators are offering to bring forth a different concept for potential treatment for obese breast cancer patients.

“If you think about the population, 1 in 8 women will develop breast cancer in their lifetime,” he said. “And if you think about how obesity increases incidence of breast cancer by 30%, there’s a huge patient population that could benefit from a different treatment regimen.”

Researchers have identified the IL-1 beta signaling pathway as a space where all the difference can be made. This pathway is affected by obesity in such a way that promotes cancer growth. Obesity influences immune cells that contribute to the production of a molecule, IL-1 beta, which in turn can increase neoangiogenesis for the cancer cells to grow.

Nothing is as simple as it sounds, but continuous support from everyone can lead to the eventual eradication of cancer and can really cure cancer patients.

“If we can interfere with this pathway and target directly the obesity-induced breast cancer progression part, we can think about how to combine the different treatments.” Ultimately, Zhang said he recommends treating the obese patients similarly to the normal-weight patients, but introducing an “obese patient specific treatment regimen” on topof the already existing treatment in the clinics.

Zhang and his collaborators have researched using breast cancer models and FDA-approved drugs to inhibit the pathway and have seen significant tumor growth difference. Although they’ve not reached the stage of clinical trials yet, their research leads them to conclude that at the clinical level, if they inhibit this pathway by genetic or pharmacological means, it’ll work! They said they believe they’ll be able to slow down cancer progression in obese breast cancer patients. Zhang’s research to better understand the role of obesity-activated signaling pathways may help explain why a drug like metformin, which has long been prescribed for control of diabetes, may also be helpful for some cancer patients.

Within the next decade, research teams hope to launch clinical trials and test new agents that can inhibit this signaling pathway. Meanwhile, Zhang’s goal is to use funding from the V Foundation to create specific antibodies that will block angiogenesis factors caused by IL-1 beta that promote cancer growth.

Zhang highlights the importance of getting from the stage of “basic science,” to the stage of “translation to human patients.” “Nothing is as simple as it sounds, but continuous support from everyone can lead to the eventual eradication of cancer and can really cure cancer patients,” he said.