Looking for Research Participants in the UK on Building Resilience Online to Counter Psychological Effects of Breast Cancer

Readers in the UK: Here's your chance to participate in research through King's College London on   the psychological effects of breast cancer, and how to build resilience through online participation. From the news release:

Worrying (thinking about how things might go badly in the future), is normal from time to time, but for most people this passes fairly quickly. However, some people find that once they start worrying, it is very difficult to stop. Research studies have shown that people who are particularly resilient experience less worry and low mood. In the present study, we hope to increase resilience and decrease low mood and worry in people who have had breast cancer. We also want to find out how people find doing the intervention via the web-platform.

For more information, and to see if you are eligible, check out The Frame Project.

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

Burn Scars: A Memoir of the Land and Its Loss

Journalist Patricia Prijatel and her family built a tiny cabin in a remote Colorado mountain valley where they embraced the silent, the wild, and the beautiful—until June 2013 and the East Peak Fire. Their cabin survived, but their woodlands became a burn-scarred landscape of splintered trunks and blackened branches.

After the fire, the ruin of the land and its people grew: flash floods on eroded land, invasive weeds crowding out grass and seedlings, hurricane-level winds breaking healthy trees, dangerous orphaned animals, toxic air, and stress leading to life-threatening diseases, including a second diagnosis of triple-negative breast cancer.

Burn Scars: A Memoir of the Land and Its Loss follows Prijatel and her family through six years of living in a changed ecosystem. It’s the story of a love of the land, of hope challenging despair, of climate grief, and the birth of a climate warrior. With searing honesty, Prijatel chronicles an unprecedented transition for America's natural forests, the life they nurture, and the people witnessing their tragic loss. Her story serves as a love song, a warning, and a glimpse of the future we'll all navigate as climate change remakes the places we've loved. It's also a call to fight for a priceless treasure we can still preserve—if we act now.

"An honest and vulnerable meditation on the trauma of life in contemporary Colorado, put to the page with uncommon grace and insight. Prijatel is a compassionate guide in exploring that chaotic time. Most important, she offers hope for recovery and resilience."
Laura Pritchett, Author, Sky Bridge, winner of the WILLA Award

"An elegy and a wake-up call. Prijatel writes a deeply personal and wrenching story of loss that touches us all. Like fire, her memoir is a reckoning that urges us to examine our priorities and recognize our first allegiance is to the earth, our one true home." Karen Auvinen, Author, Rough Beauty: Forty Seasons of Mountain Living.

"A moving meditation on our connection to the land, and a potent wake up call to the devastating effects of climate change."Tanja Pajevic, Author, The Secret Life of Grief, winner of Nautilus Silver Award"

"An important story. Prijatel chronicles her personal journey of loss and climate grief that touches our collective experience. But it is also a story of healing, for as we face this crisis, we are challenged to discover a resilience within ourselves and in the generative power of nature." Leslie Davenport, Author, Emotional Resiliency in the Era of Climate Change.

Buy Burn Scars: A Memoir of the Land and Its Loss on Amazon

Get an autographed copy directly from the author.

Inflammation Caused by Radiation Can Fuel TNBC Cells: A New Road To TNBC-Specific Treatment?

From a News Release from ChristianaCare’s Cawley Center for Translational Cancer Research 

While radiation is successfully used to treat breast cancer by killing cancer cells, inflammation caused as a side-effect of radiation can have a contrary effect by promoting the survival of triple-negative breast cancer cells, according to research published online in the International Journal of Radiation Biology by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute.

Accounting for 15-20% of all breast cancers, triple-negative breast cancer is faster growing than other types of breast cancers.

Dr. Sims-Mourtada’s latest study shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem TNBC cells.

“This is the good and the bad of radiation,” Dr. Sims-Mourtada said. “We know radiation induced inflammation can help the immune system to kill tumor cells — that’s good — but also it can protect cancer stem cells in some cases, and that’s bad.”

She added, “What’s exciting about these findings is we’re learning more and more that the environment the tumor is in – its microenvironment – is very important. Historically, research has focused on the genetic defects in the tumor cells. We’re now also looking at the larger microenvironment and its contribution to cancer.”

Triple-negative breast cancer cells don’t have estrogen or progesterone receptors and also don’t make too much of the protein called HER2—cells test “negative” on all 3 tests. These cancers tend to be more common in women under age 40, who are African-American, Latina or who have a BRCA1 mutation. But older women, caucasian, those with no family history of breast cancer, and no genetic mutations can be affected.

“My work focuses on cancer stem cells and their origination,” Dr. Sims-Mourtada said. “They exist in many cancers, but they’re particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth.”

She and her team applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. As yet unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.
For women living in Delaware, Dr. Sims-Mourtada’s research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

Dr. Sims-Mourtadato recently received a grant to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and a possible TNBC-specific therapy.“Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing,” she said.

Her research team previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.

Researchers Starve Triple Negative Breast Cancer With Drug in Clinical Trials

From A News Release from Science Daily

Brazilian researchers have developed a strategy that slows the growth of triple negative breast cancer cells by cutting them off from two major food sources.

Triple-negative breast cancer, or TNBC, makes up approximately 15% to 20% of all breast cancers and is most common in African American women. These tumors lack estrogen and progesterone receptors and HER2 protein which are present in other breast cancers and permit certain targeted therapies. And because every TNBC tumor has a different genetic makeup, finding new markers that could guide treatment has been a difficult task.

"There is intense interest in finding new medications that can treat this kind of breast cancer," said Sandra Martha Gomes Dias, a cancer researcher at the Brazilian Biosciences National Laboratory in Campinas, Brazil. "TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer, mainly because there are fewer targeted medicines that treat TNBC."

In a new study in the Journal of Biological Chemistry, Dias and colleagues demonstrate that in addition to glutamine, a well-known cancer food source, TNBC cells can use fatty acids to grow and survive. When inhibitors that block both glutamine and fatty acid metabolism were used in concert, TNBC growth and migration slowed, Dias said.

To maintain their ability to grow at a breakneck pace, cancer cells consume nutrients at an increased rate. Glutamine, which is the most abundant amino acid in plasma, is one of them. Some types of cancer become heavily reliant on this versatile molecule as it offers energy, carbon, nitrogen, and antioxidant properties, all of which support tumor growth and survival, Dias said.

The drug Telaglenastat, also known as CB-839, prevents the processing of glutamine and is currently in clinical trials to treat TNBC and other tumor types. CB-839 works by deactivating the enzyme glutaminase, preventing cancer cells from breaking down and reaping the benefits of glutamine. However, recent research has shown that some TNBC cells can resist the drug treatment.

To see if alterations in gene expression could explain how these cells survive, the authors of the study exposed TNBC cells to CB-839, defined those that were resistant and those that were sensitive to the drug, and sequenced their RNA, Dias said.

In the resistant cells, molecular pathways related to the processing of lipids were highly altered, Dias said. In particular, levels of the enzymes CPT1 and CPT2, which are critical for fatty acid metabolism, were increased.

"CPT1 and 2 act as gateways for the entrance of fatty acids into mitochondria, where they will be used as fuel for energy production," Dias said. "Our hypothesis was that closing this gateway by inhibiting CPT1 in combination with glutaminase inhibition would decrease growth and migration of CB-839-resistant TNBC cells."

The double inhibition proved significant as it slowed proliferation and migration in resistant TNBC cells more than individual inhibition of either CPT1 or glutaminase. These results provide new genetic markers that could better guide drug choice in patients with TNBC, Dias said.

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Metabolic Syndrome and TNBC

Improving metabolic factors may help improve survival in postmenopausal women with triple-negative breast cancer, according to research presented at the 2019 San Antonio Breast Cancer Symposium. These factors, which include weight gain, reduced activity and insulin resistance, can be an issue for women diagnosed with TNBC and may have serious repercussions for health overall. 

Researchers compared these factors, also called metabolic syndrome, with survival rates in women diagnosed with TNBC who participated in the Women’s Health Initiative (WHI), enrolled from 1993 to 1998. 

The average time from enrollment to TNBC diagnosis was 8.6 years; women with the most metabolic components had a significantly shorter time (7 years) to diagnosis than those without any metabolic syndrome components (9.8 years). Women with TNBC and 3 to 4 metabolic components had 10-year all-cause survival rates 35% lower than TNBC survivors with no metabolic syndrome components.

• 29% of the women (178 patients) had no metabolic syndrome components.

• 53% had 1 to 2 components (323 patients).

• 7% had 3 to 4 components (43 patients). 

• Those with the most metabolic syndrome components were often black. 

• Patients with income under $50,000 a year were more likely to have a greater number of metabolic components. 

The conclusion: Greater attention should be given to issues such as weight gain, physical activity, and insulin levels. 

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