HDAC6 Effective in Metastatic TNBC

A news release from the George Washington University (GW) Cancer Center. 

Genetic modifier HDAC6 was found to control tumor growth and halt metastasis in triple-negative breast cancer in vivo, according to a new study published in the journal Cancer Research by investigators at the George Washington University (GW) Cancer Center.

Immunotherapy – the use of drugs to stimulate one’s own immune system to recognize and destroy cancer cells – has been successful in melanoma and other cancers. However, it has been less effective in breast cancer.

“There is an urgent medical need to find new ways to potentiate or increase the efficacy of immunotherapy in breast cancer, especially in aggressive and highly metastatic triple-negative breast cancer,” said Alejandro Villagra, PhD, member of the Cancer Biology Program at the GW Cancer Center and assistant professor of biochemistry and molecular medicine at the GW School of Medicine and Health Sciences. “Our research lays the groundwork for a clinical trial that could lead to new, life-saving treatment options for breast cancer patients that do not respond to conventional immunotherapies.”

Molecularly targeted agents, such as HDAC6 inhibitors, have been widely described in the research literature as cytotoxic – toxic to both cancerous and healthy cells. Villagra and his research team found new non-canonical regulatory properties of these epigenetic drugs, discovering that the inhibition of HDAC6 has a powerful and strong effect on the immune system unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.

This research demonstrates for the first time that HDAC6 inhibitors can both improve response to immunotherapy and diminish the invasiveness of breast cancer, with minimal cytotoxic effects.

“We are excited about the work because, in addition to the potency of immunotherapy, this drug alone is capable of reducing metastasis,” said Villagra. “This could have implications beyond breast cancer.”

TNBC and CDK4/6 Inhibitors

Some good information here (OncLive) about TNBC and CDK4/6 Inhibitors, especially clarifying the different types of TNBC. Scroll toward the bottom of the article. 

An excerpt, from Ruth O’Regan, MD. chief of the Division of Hematology, Medical Oncology and Palliative Care within the Department of Medicine and associate director of Clinical Research at the University of Wisconsin Carbone Cancer Center:

However, when you look at TNBC, there is not just 1 type of breast cancer; there are 4 to 6 different types under that triple-negative umbrella. One of them is the luminal AR subtype, which looks like a luminal ER-positive subtype genomically, but is actually ER negative and AR positive. This led to some trials looking at single-agent antiandrogens to treat these AR TNBCs. Overall, both enzalutamide (Xtandi) and bicalutamide (Casodex) produced pretty modest activity. The question become, “How could we make these antiandrogen drugs more effective in these AR-positive TNBCs?” 

Need a Respite?

I had thought I was doing a decent job managing the stress of the pandemic, social unrest, my cancer advocacy and concerns, economic instability, the climate crisis, and everything that is 2020. I wasn't. 

Here's how nature helped and how it might help you too. 

Double rainbow on the ridge opposite my deck.

A deep sigh overwhelmed me as I sat down with a cup of tea on the deck of our mountain cabin—a shock down my neck, through my tense shoulders, to my arms, and into my clenched fingers. An unexpected, visceral response.

For a moment, I sat unmoving as my muscles contracted, then relaxed, and relaxed more. It felt almost violent. An emotional exorcism.

I often exhale a long, healthy sigh on this deck, a natural reaction to the miraculous calm and quiet before me. I look out at a meadow, across a tiny stream, over to a forested ridge. To my right looms the mountain in whose shadow we spend the summers.  

But this new reaction was far beyond that simple act of deep breathing. It felt more like an attack.

I had thought I was doing a decent job managing the stress of the pandemic, social unrest, my cancer advocacy and concerns, economic instability, the climate crisis, and everything that is 2020. That’s an incomplete list, and even reading it is stressful. I knew I was traumatized, but I was sure I was handling it just fine, what with being me and all.

Or not.

Our hummingbird feeder attracts gorgeous guys like this. You can put a feeder just about anywhere.

As I sat down in the mountain sun, I had unconsciously unleashed a batch of negative emotions that had skittered out of my body like little demons: fear, anxiety, anger, grief, stress, confusion, depression, disgust. More, I’m sure.

Most of us are facing post-traumatic stress disorder after the year that feels like a lifetime—and, in many ways, is. Those of us with cancer in our histories are especially susceptible to PTSD, even years after a diagnosis. How do we keep our lives, our communities, our country, and our planet afloat when we’re all hot zones of trauma? READ MORE