Inside the Lab: Preventing breast cancer from invading the brain

July 24, 2017 | by Denise Heady

Rahul Jandial in the lab Neurosurgeon and Scientist Rahul Jandial, M.D., Ph.D.

Unfortunately, cancer cells are smart.

Even if a patient achieves clinical remission with negative scans and blood work, microscopic cells can sprout new tumors. The cruelest cells break away from their original tumor site and metastasize (spread) to other parts of the body — requiring treatment on multiple fronts.  

Metastasis is a complication of cancer and responsible for the majority of cancer deaths. Nearly 40 percent of all women with HER2-positive breast cancer will develop brain metastases.

A study led by City of Hope neurosurgeon and scientist Rahul Jandial, M.D., Ph.D., and staff scientist Khairul Ansari Ph.D., offers novel insights on how cancer cells in HER2-positive breast cancer develop the ability to break through the blood-brain barrier and, ultimately, how they can be stopped.

Jandial and his team, who investigate the biology of cancer metastasis to the brain, found that one key biological element is a brain receptor (neurotrophin receptor TrkB) that typically is not found on tissue from other organs. Surprisingly, breast cancer cells that successufully seed the brain also sprout these brain receptors. Other breast cancer cells armed with neurotrophin receptors can be empowered from the  growth factors that are naturally abundant in the brain.

breast cancer cells JANDIAL 256 x 256 Metastasis is a complication of cancer and responsible for the majority of cancer deaths. Nearly 40 percent of all women with HER2-positive breast cancer will develop brain metastases.

The study, published in this month’s issue of Breast Cancer Research, suggests that by inhibiting these receptors, cancer cells may not be able to colonize the dynamic biological landscape of the human brain.

Here, Jandial, associate professor in the Division of Neurosurgery, discusses the study and how pinpointing these receptors ties to brain metastases holds therapeutic potential.  

How does HER2+ breast cancer find its way to the brain?

Likely by using any advantage that leads to expansion to other organs. We hope that some of these adaptations can be disrupted and, along with the brain’s innate cellular and molecular defense mechanisms, allow for clinical suppression of brain metastases.

Why does this type of breast cancer have a high risk of developing metastases to the brain?   

Clinically, we know this is happening since our patients’ cancer journeys reveal this. Biologically, that remains a mystery and that’s why my lab is investigating it.

Why look into the receptor TrkB? And what is TrkB?

We reasoned that since the brain is rife with growth factors and neurochemicals that maintain a healthy brain, a cancerous intruder would be most likely to succeed if it could adapt/evolve the ability to utilize these native molecular cues as drivers of malignant growth. 

What’s next?

We’ll explore if disrupting brain receptors on breast cancers cells with medicine will lead to less tumor growth. Ultimately, cancers have biological Achilles' heels andexploiting these weaknesses is what scientific investigation and drug discovery is about.

What do your findings mean for our understanding of cancer?

Cancer is not one entity. At a cellular level, cancer cells are evolving and fighting for their existence and willing to adapt in unexpected ways to survive. Their biological flexibility and insatiable drive to flourish is what makes them so formidable. 

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