Monday, December 30, 2019

Combination Immunotherapies Offer New Hope for Chemotherapy-Resistant Ovarian Cancer Patients

This is another example of how your tax dollars are working to find cures for particularly deadly types of ovarian cancer.

The Congressionally Directed Medical Research Program (CDMRP) awards $20 million dollars each year for research into ovarian cancer. But each year, Congress has to allocate this money and we continue to hope that in 2020, this research will again be funded.

I have had the privilege and honor to have served  in 2016, 2017 and 2019 as a consumer advocate to award these grants. Although consumer advocates and other members of the panel are never at liberty to discuss individual applications for funding, each year, CDMRP posts on their website, the results of those who have received funding. You can find out more about this by following this link.

In the meantime, here is an article about the oncolytic viruses used in immunotherapy in the treatment of OC. As many of our readers know, immunotherapy is not consistently effective in treating OC. Research by Dr. Dmitry Zamarin out of Sloan Kettering, may shed light on why that is...

Immunotherapy has emerged as a promising approach for ovarian cancer treatment. It enables patients’ immune systems to target cancer cells, and it may be effective where other chemotherapy and radiation have failed. Dr. Dmitriy Zamarin’s research focuses on understanding the mechanisms of immunotherapy in cancer with the hope of identifying new treatments for ovarian cancer patients. To facilitate a career as an independent investigator with a focus in immunotherapy and ovarian cancer, Dr. Zamarin sought support from the Ovarian Cancer Academy. In fiscal year 2015 (FY15), he received an Ovarian Cancer Academy – Early-Career Investigator Award, and with its support, he has investigated biomarkers indicating response or resistance to immunotherapies and developed novel immunotherapeutic ovarian cancer treatment strategies. Impressively, Dr. Zamarin’s research has resulted in a phase II clinical trial focusing on a treatment for ovarian cancer patients that are resistant to standard therapies.
With support from the FY15 award Dr. Zamarin found potential benefits for the use of immunotherapies in ovarian cancer patients, but also noticed limitations. When investigating the use of Programmed Cell Death Receptor 1 (PD-L1) inhibitor drugs, which block the receptors that enable cancer cells to evade the body’s immune response, Dr. Zamarin noted some success in ovarian cancer patients, but the responses were variable, as some patients did not respond to treatment. Dr. Zamarin also researched another type of immunotherapy that has recently emerged: oncolytic viruses (OVs). These molecules selectively target and infect tumor cells, marking them for destruction by the body’s immune system without harming normal tissue. What’s more, in addition to killing injected tumors, OVs induce destruction of distant tumors through the body’s generation of an anti-tumor immune response. Dr. Zamarin determined that OVs increased tumor cell death by the immune system; however, this success was limited by the tumor’s continued expression of PD-L1, which interfered with tumor cell death. 
Based on these results, Dr. Zamarin hypothesized that the application of PD-L1 inhibitors with OVs could prove to be a more effective treatment in ovarian cancer patients. By combining OVs and PD-L1 inhibitors, enhanced activation of the immune response to the tumor, along with tumor regression, was promoted in animal models, an effect that was not seen with either treatment alone. This exciting finding led Dr. Zamarin and colleagues to develop a phase II clinical trial to test the therapeutic combination of an OV, ONCOS-102, and PD-L1 inhibitor, durvalumab, in patients with ovarian cancer that has developed resistance to standard therapies. This trial is currently ongoing. 
Along the same lines, Dr. Zamarin and colleagues are studying whether activation of anti-tumor immune responses using anti-cancer vaccines could boost the efficacy of PD-L1 inhibitors. They have conducted a combination phase II trial of TPIV200, a vaccine targeting folate receptor, with the PD-L1 inhibitor, durvalumab, in patients that failed to show response to standard ovarian cancer treatment. Twenty-seven women with advanced ovarian cancer were enrolled in the trial. Post-immunotherapy follow-up showed an increase in patient survival, suggesting improved clinical benefit from the combination immunotherapy and warranting further exploration of the combined treatment. 
Resistance to chemotherapy is a major problem for women with advanced ovarian cancer, and alternative treatments are desperately needed. Dr. Zamarin’s research into a novel combined immunotherapy provides hope for women in the advanced stages of this disease.

This article was reposted from the CDMRP website.

Monday, December 23, 2019

A Collaborative Effort has Uncovered Novel Therapies to Treat an Aggressive Form of Ovarian Cancer That is Unresponsive to Standard Treatment

The Congressionally Directed Medical Research Program (CDMRP) through the Department of Defense awards $20 million/year on ovarian cancer research.

This research was led by Dr. Konstantinopoulos from Dana Farber. His team uncovered a protein that makes one of the most deadly types of ovarian cancer resistant to chemotherapy.

We are indeed fortunate to live in the Northeast where woman with ovarian cancer can access care at these centers of excellence.

I am reposting the article that appeared on the CDMRP website about this research.

The Ovarian Cancer Research Program (OCRP) formed the Ovarian Cancer Academy to bring together talented and highly committed Early-Career Investigators (ECIs) along with experienced mentors to help establish the ECIs as successful and highly respected ovarian cancer researchers. To create an opportunity for the ECIs to form meaningful and productive collaborations both within the Academy and in the ovarian cancer research community, the OCRP offered the Ovarian Cancer Academy Collaborative Award in fiscal year 2014 (FY14). The award stipulated that the proposed collaboration be led by an Initiating Principal Investigator (PI) from the Academy and a team consisting of Partnering PIs, which could be other ECIs or independent investigators not affiliated with the Academy.
A team led by Dr. Panagiotis Konstantinopoulos was awarded the FY14 Ovarian Cancer Academy Collaborative Award. The other members of the team include fellow ECI Academy member Dr. Rugang Zhang and Dr. Dipanjan Chowdhury, who was not a member of the Academy.  The project aimed to develop strategies against cyclinE1 (CCNE1) amplified ovarian cancer, the most deadly ovarian cancer due to a lack of responsiveness to standard chemotherapy. Excitingly, the team has had success in identifying and validating heat shock protein 90 (HSP90) as a novel therapeutic target. 
The functional homologous recombination (HR) in CCNE1 amplified cells allows them to repair the DNA damage caused by chemotherapy, making them chemoresistant. HSP90 is a chaperone protein that assists proteins, including CCNE1 and those involved in HR, to fold properly. The team hypothesized that the inhibition of HSP90 would interfere with HR and downregulate CCNE1, and, alone or in combination with other DNA damage inducing drugs, may induce lethality in CCNE1 amplified cells.
The team’s results revealed that HSP90-inhibition downregulates HR DNA repair in CCNE-1 amplified cell lines and induces significant cell death. They determined that an HSP90-inhibitor, AT13387, synergized with DNA damage inducing agents, such as PARP-inhibitors, and enhanced cell death in CCNE1-amplified cell lines. Next, the team assessed the effects of the combination treatment of HSP90-inhibitors and PARP-inhibitors in patient derived CCNE1-amplified ovarian cancer tumors in a mouse model. They determined that the combination treatment inhibited tumor growth and was more effective than either treatment alone, suggesting that HSP90 inhibitors in combination with PARP-inhibitors may be an effective treatment for CCNE1-amplified ovarian cancer.
These impressive results supported by the OCRP have led to the initiation of a Phase 1 clinical trial of the PARP inhibitor, olaparib, and HSP90 inhibitor, AT13387, for the treatment of recurrent ovarian cancer and other metastatic solid tumors. If successful, this trial could validate this novel therapeutic strategy to treat patients with CCNE1-amplified ovarian cancer tumors who have poor outcomes due to the ineffectiveness of standard treatment.

Tuesday, December 17, 2019

Some Helpful Organizations To Check Out

A big thank you to Dawn for forwarding me this list of links that she's found helpful.

FAB treats all skin related side effects due to chemo. Dawn said that they offer so many wonderful integrative therapy options that she didn't know how to describe it all while doing justice to it!

Patient Access Network 
How to pay for expensive medicine

Helping Hands Program (A program of OVATIONS)
Delivers free healthy meals for women with ovarian cancer
Massachusetts only

Yoga and Cancer
Provides free specialized yoga and support for patients, survivors and caregivers in the New Hampshire seacoast and southern Maine area

Look good feel good
Offers two free programs. One teaches you how to apply make up including eyebrows. The other teachers about skin care. You can attend these programs in person or virtually. 

A mobile app that uses artificial intelligence to help cancer patients optimize their treatment. Track your symptoms, get medication reminders, and work activities to gain insights. 

Friday, December 13, 2019

Managing Recurrence of Ovarian Cancer Th., Dec. 19th, 6pm EST

Ovarian Cancer Research Alliance is sponsoring a free webinar on how to manage a recurrence of OC.

Dr. Kathryn Pennington will discuss the diagnosis and management of this. She is a gyn/onc from the University of Washington.

So bring your questions and join in on the conversation. To register, follow this link.

If you can't make the live webinar, you can sign  receive a link to the full recording when it is available.

Surgery for Recurrent Ovarian Cancer Does Not Improve Survival

I must say that I had to read this article twice because the study results were just so stunning to me! Again, I have Betsy to thank for sending this to me.

Essentially, women who have surgery for recurrent OC (epithelial, primary peritoneal or fallopian tube cancers) were included.

The results showed that women who did not have surgery lived 14 months longer than those who had surgery plus chemo and Avastin. They also had a better quality of life given that they didn't have all the post-op hassles to deal with.

To read about this in (far) more interesting detail, I'm providing several links: one from the National Cancer Institute (NCI) which summarizes the study and another from National Center for Biotechnology Information (NCBI) that provides the abstract of the study itself published by NCI.

Here they are:
Surgery for Recurrent Ovarian Cancer Does Not Improve Survival 

Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial.

Thursday, December 5, 2019

OCRA-Funded Research Provide More Insights into Clear Cell OC

OCRA-Funded Research Yields Insight into Clear Cell Ovarian Cancers

(November 13, 2019) A study recently published in Nature Communications and led by OCRA grantee Dr. Rugang Zhang showed that the ARID1A protein plays a fundamental role in ensuring correct chromosome segregation when the cells divide.
Specifically, ARID1A controls expression of another protein called STAG1 that is required to keep chromosome ends together. When ARID1A function is lost due to mutations, the levels of STAG1 decrease and, as a consequence, cells accumulate gross chromosomal alterations that are not compatible with cell survival. Loss of ARID1A therefore pushes a selection process that favors cells lacking genomic instability.
Although ARID1A is known to act as a guardian of genome integrity, researchers could not explain why cancer types with high frequency of ARID1A mutations are not typically associated with genomic instability. “Our findings may elucidate this apparent paradox and partly explain why clear cell ovarian cancers typically respond poorly to chemotherapy agents that target cell division,” said Dr. Zhang.
Learn more about the study through WISTAR Research Institute, or read the full publication at Nature Cell Biology.
Reprinted from OCRA

Tuesday, December 3, 2019

Survivors Teaching Students

We talked about Ovarian Cancer Research Alliance's program (OCRA), "Survivors Teaching Students" (STS) at our 2019 retreat.

This outstanding program sends a team of three ovarian cancer survivors in to talk with medical and nursing students about their own experiences with symptoms before they were diagnosed. As we know, OC symptoms are often vague and easily attributed to other benign illness like irritable bowel syndrome (IBS), or worse, our symptoms were ignored. Our stories serve as powerful reminders for these students as they enter their careers.

Diane Riche is the New England Coordinator for STS. She kindly sent me a detailed guide to how the program is structured. I am including it below for those of you who are interested in joining one of the teams near you - or starting a team of your own! Information is also available from the OCRA website. Feel free to contact me or Diane for further info.

We hope ups choose to join the Survivors Teaching Students: Saving Women’s Lives®, a program of the Ovarian Cancer Research Alliance! You would be joining an innovative and critical effort to educate students in health professional programs nationwide about ovarian cancer. Our goal is to increase the number of health care providers who recognize the risk factors and symptoms of ovarian cancer so that the disease is detected earlier.
As you are aware, the majority of ovarian cancer cases are not diagnosed until the disease is advanced and women’s survival is compromised. The symptoms may not be recognized early enough and too often women who are at high-risk are not identified and monitored. Survivors Teaching Students® brings the faces and voices of ovarian cancer survivors into the classrooms of health professional students to teach them about women’s experiences with the disease. We are in a unique position to help students become more sensitive to the risks and symptoms of ovarian cancer so that when they go into practice they can diagnose women sooner and save lives.
Ovarian cancer is the fifth leading cause of cancer-related death among women in the United States and causes more deaths than any other cancer of the female reproductive system. The majority of cases are not diagnosed until the disease is far advanced and women’s survival is compromised. Symptoms may not be recognized early enough, and too often, women who are at high risk are not identified or monitored.
To address the issue of early detection, Ovarian Cancer Research Alliance conducts the Survivors Teaching Students: Saving Women’s Lives® (STS) program. The goal of the program is to enhance health professional students’ understanding of ovarian cancer symptoms and risk factors in order to facilitate earlier diagnosis and detection. Betty Reiser, former Program Director and long-time ovarian cancer survivor, played a leading role in its facilitation and expansion.

Program Description
STS achieves its goal by bringing ovarian cancer survivors into the classrooms of health professional students. The survivors share their stories and key information on the disease. The program is currently offered to a variety of medical and health professional students—our future diagnosticians—including medical, nurse practitioner, physician assistant and nursing students.
The program lasts approximately one hour, during which ovarian cancer survivors deliver crucial messages about the risks and symptoms of ovarian cancer. They also explain appropriate referrals for women suspected of having ovarian cancer. 
Presentation Guidelines
  • Each presentation should last one hour, and follow the schedule below:
    • Introduction—five minutes (On-site Facilitator—see description below)
    • Administer and Collect Pre-Evaluations—five minutes
    • Presenter #1—seven minutes
    • Presenter #2—seven minutes
    • Presenter #3—seven minutes
    • Question and Answers—15-20 minutes (Note: This is flexible and may last longer depending on time.)
    • Closing—five minutes (On-Site Facilitator)
    • Distribute Handouts and Administer Post-Evaluations—five minutes
  • The presentation typically includes three presenters—one of whom may also serve as the facilitator—who are ovarian cancer survivors. Ideally, presenters should be women with different backgrounds and experiences. In many cases, the women who present will have been diagnosed at a late stage, but it is valuable to include women diagnosed at an early stage as well.
  • The facilitator will begin the presentation with a brief introduction. Next, each presenter tells her story, illustrating the difficulty of early diagnosis and what happened to her as a result. The survivor’s story puts a face and voice to the disease, which is a powerful tool in increasing students’ understanding and recall of the facts about ovarian cancer.
  • Students should gain insights into listening to patient concerns and become sensitized to the psychosocial aspects of ovarian cancer, as well as the need for early detection.
  • After the presentation, the facilitator will open a dialogue between the presenters and students to enable direct and substantive interaction.
  • Students are also given a brief pre and post evaluation to assess their understanding of the disease and the value of the presentation (see: Appendix).
  • The STS presentation is offered free of charge to health professional schools.

          The New England area currently presents at 8 schools, some are medical students (presentations are every 6 weeks) or nursing/physician assistant programs (and those presentations are once a semester). Times of day vary.
As the school schedules are given to your area coordinator she will send out a group email to see who is available on dates given. 

Sunday, December 1, 2019

Ovations for the Cure On-line Auction Ends Dec. 5th

Ovations for the Cure of Ovarian Cancer is holding its annual Online Holiday Auction which ends on Dec. 5th.

Items include vacation getaways, gift certificates from all manner of restaurants, services and retailers and cool items like Bose microspeakers!
To bid on any of the 91 items, follow this link.

All proceeds go to fund Ovations mission of providing research, awareness and patient programs. In fact, I was so impressed by the some of the research programs it has supported that I thought it of interest to include:

Ovations for the Cure of Ovarian Cancer supports various research, awareness and patient programs each year. To date, we have directed over $1.5 million to ovarian cancer research initiatives and treatment programs. Here's where it has gone:
  • $660,607 to the Dr. Ursula Matulonis-Madeline Franchi Fund at Dana-Farber Cancer Institute
  • $350,000 to Brigham and Women's Hospital to fund the Desensitization Program
  • $150,000 to Dana-Farber Cancer Institute for a Desensitization Suite
  • $147,672 to the Ovations for the Cure of Ovarian Cancer Research Fund at Dana-Farber Cancer Institute through the two AM Fund
  • $60,000 to City of Hope Cancer Center in Los Angeles, CA
  • $50,000 to University of Pennsylvania's Biomarkers study
  • $45,810.50 to Dana-Farber Cancer Institute
  • $40,000 to Children's Hospital Boston for Early Detection Research
Again, to bid on any of the 91 items, follow this link.

Monday, Dec. 2nd Webinar About the Legal (and Other) Resources for Caregivers of Women With Ovarian Cancer

Here's an important Webinar that details resources for caregivers. The topics cover the legal rights for caregivers taking time off from work, wage replacement and more.

The webinar is easy to sign up for and lasts one hour. It's on Monday, Dec. 2nd at 6 pm.

Here's the link to join.

Yummy Cookie Recipe from 2019 TTT Retreat

Do you remember those great Vegan Peanut Butter Cookies that we had at our retreat this year? Well, Anne sent me the recipe that she got from her daughter, who got it from

Here it is!!

Secret Vegan Peanut Butter Cookies
Yield: 7-10 cookies

1/2 c peanut butter (I used crunchy)
3/4 t baking soda
3 T flour (any kind will work, I used 1-to-1 gluten free)
1/3 c sugar
2 T applesauce
1/2 t vanilla extract
1/8 t salt

Preheat oven to 350 degrees F. Line cookie sheet with parchment paper.

Combine dry ingredients. 
Add all remaining ingredients and stir to form a dough. 
Roll into 1-inch balls. Place them on the cookie sheet and press with a fork. For softer cookies, refrigerate the formed dough for at least an hour before baking.
Bake for 8 minutes. Let cool for at least 10 minutes on the baking sheet. (The cookies will look underdone when they come out of the oven and firm up as they cool.)

Tuesday, November 12, 2019

2019 TTT Retreat Video: Coming Soon!

I'm still basking in the magic that happens each year at this wonderful retreat where women from NE come to gather. It doesn't matter that some of us come for the first time because by the end of our time together, we have deepened our bonds with each other.

It's hard to put into words just how special this connection is except to say that for 4 nights/5 days, we are free to express ourselves in unguarded ways. We talk about the hard stuff, we laugh, we cry, we play, we luxuriate in the generous services offered to us by skilled, loving practitioners who provide us with massage, facials, reflexology, yoga, morning walks, indoor rock climbing, archery, special arts/crafts - well I hope you get the picture.

Eva Kasell, our photographer, lovingly and unobtrusively captures all of this so stay tuned for a video that will be posted as well as photos of our time together.

There just aren't words to adequately thank Anne Tonachel, Sue Joanis and Christine Barilone and all the women who volunteered their time and services, not to mention all the people and organizations that donated gifts. Not only do we have memories to sustain us but we also have a loving sisterhood to help us on our journeys.

Tuesday, November 5, 2019

Clear Cell Ovarian Cancer and Endometriosis

This article was published by Ovarian Cancer Research Alliance (OCRA) which funded the project. A link to the original research article can be found here.

(September 10, 2019) Ovarian clear-cell carcinoma is an aggressive form of ovarian cancer.  Endometriosis is derived from the uterine endometrium and is a known risk factor for ovarian clear-cell carcinoma.  Evidence supports ovarian clear-cell origins in the uterine endometrium.   It has been known for years that co-occurring cellular mutations are observed in ovarian clear-cell carcinoma, but the consequences of these (ARID1A and PIK3CA) mutations in the endometrial epithelium were previously unknown.
In a recent article in the journal Nature CommunicationsDr. Ronald Chandler’s lab uncovered a new role for specific mutations in a cellular process called collective epithelial cell migration.  Collective migration describes the movement of groups of cells.  Dr. Chandler’s lab provides evidence that collective migration allows abnormal cells to spread to outer areas within the female reproductive tract.  His lab’s findings help explain why these mutations are observed in ovarian clear-cell carcinoma and other diseases or cancers derived from the endometrial epithelium, including endometriosis.
Dr. Chandler’s research supports the idea that, to understand the causes of ovarian cancer, researchers should focus their attention on non-ovarian tissues in the female reproductive tract, such as the fallopian tubes and uterine endometrium, because mutations alone do not explain all aspects of the disease.
More information can be found in the original Nature Communications article.

Wednesday, October 30, 2019

Genetically Definable Subgroups of Cancers Sensitive to Treatment

This article was originally published by News-Medical.

Precision oncology aims to use genetic features of a patient's tumor to tailor anti-cancer therapy. DNA mutations in a drug target have provided a number of therapeutic opportunities; however, there are many cancer types that do not have obvious targetable mutations. A research team at Dartmouth's Norris Cotton Cancer Center led by Todd Miller, PhD, sought to determine whether genetic features could be used to identify novel cancer "subtypes" that span multiple organ sites, and whether this approach could be useful to identify novel treatment strategies.
Miller's team successfully demonstrated that genetic and drug sensitivity data from cancer cells can be used to reveal therapeutic vulnerabilities that transcend cancer lineage. Their results, "A transcriptionally-definable subgroup of triple-negative breast and ovarian cancer samples shows sensitivity to HSP90 inhibition" have recently been published in AACR's Clinical Cancer Research.

"We discovered that a novel, genetically definable mixed subgroup spanning both triple-negative breast cancer and ovarian cancer is vulnerable to treatment with heat shock protein 90 (HSP90) inhibitors. HSP90 inhibitors have been investigated as potential anti-cancer drugs for many years in clinical trials guided by organ site, but tumor response rates have been low. We postulate that testing such drugs in a genetically defined subpopulation of patients would increase response rates."
Todd Miller, PhD, at Dartmouth's Norris Cotton Cancer Center

The team's findings suggest that genetic signatures may be useful to identify cancer subgroups that transcend organ site/lineage and are sensitive to a given class of therapeutics. Future steps include a clinical study using the genetic signature to determine whether it predicts sensitivity to HSP90 inhibitors.

Friday, October 25, 2019

Using A.I. to Transform Breast Cancer Care

Although I do not normally post articles about breast cancer, this article from the N.Y. Times intrigued me because the same principles I think, can be applied to ovarian cancer.

A. I. is "artificial intelligence" and Dr. Regina Barzilay, a computer science professor at M.I.T. and a recipient of the MacArthur genius award in 2017, herself a breast cancer survivor, is focusing her work on helping other women with breast cancer. Her goal is to develop algorithms to determine who is likely to develop breast cancer in the next five years, taking into account the subtle changes noted on mammograms.

To read more about this amazing research, follow this link.

Friday, October 4, 2019

Congratulations to our own Donna Wiegle!!

It didn't take Donna long to move from an idea of riding cross-country to making it happen during the month of September - ovarian cancer awareness month. Her goal was simple - to talk to anyone and everyone about the signs and symptoms of OC while raising money to support two great causes: Ovations for the Cure of OC and our own Turning-the-Tide Ovarian Cancer Retreats, Inc.

When musing about how much money she should set as her target, she decided go big - $50,000. And she is just shy of that goal. But I'm getting ahead of myself....

For those of us who know Donna, when she sets her mind to something, she makes it happen. When an elderly member of her small community on Swan's Island off the coast of ME was dying, she cooked meals, mowed his lawn, and took care of him.

There was no health care facility on the island, so she started one. It has state-of-the-art telemedicine equipment and here Donna holds classes for the residents, offers blood pressure clinics, arranges for doctors to come to regularly and provide services - in short, she does everything from cleaning the bathroom to drawing blood, saving residents the expense in time and money from leaving the island.

So when the idea of riding a motorcycle cross country and educating men and women about OC, it wasn't a stretch to imagine Donna doing this. She's that kind of woman. When she came across a teal and white Harley for sale one day on the mainland, it didn't take long for the threads of her plan to spin out. She eventually bought the motorcycle, had it specially outfitted for a long journey with the help of her husband Charlie, and the generosity of a local bike shop. She had business cards made up, she received hundreds of cards listing the symptoms of OC from OCRA, got a really cool leather vest inscribed with her logo, "Teal on Wheels", had a flag made up and set her eyes on starting in Oregon for a month long journey.

What has inspired her so much is the generosity of people she has met along her journey - people paying for her meals, handing her $100 bills, even joining in to ride with her along the way. She chronicled her journey on her FB page.

If you haven't yet donated and would like to, you can by following this link to her GoFundMe page.

Thursday, September 26, 2019

Body-on-a-Chip Device Predicts Cancer Drug Responses

Thanks go out to Betsy for sending me this article from the NIH Director's Blog, written by Dr. Francis Collins:

Researchers continue to produce impressive miniature human tissues that resemble the structure of a range of human organs, including the livers, kidneys, hearts, and even the brain. In fact, some researchers are now building on this success to take the next big technological step: placing key components of several miniature organs on a chip at once. 
These body-on-a-chip (BOC) devices place each tissue type in its own pea-sized chamber and connect them via fluid-filled microchannels into living, integrated biological systems on a laboratory plate. In the photo above,(NOT SHOWN), the BOC chip is filled with green fluid to make it easier to see the various chambers. For example, this easy-to-reconfigure system can make it possible to culture liver cells (chamber 1) along with two cancer cell lines (chambers 3, 5) and cardiac function chips (chambers 2, 4). 
Researchers circulate blood-mimicking fluid through the chip, along with chemotherapy drugs. This allows them to test the agents’ potential to fight human cancer cells, while simultaneously gathering evidence for potential adverse effects on tissues placed in the other chambers. 
This BOC comes from a team of NIH-supported researchers, including James Hickman and Christopher McAleer, Hesperos Inc., Orlando, FL. The two were challenged by their Swiss colleagues at Roche Pharmaceuticals to create a leukemia-on-a-chip model. The challenge was to see whether it was possible to reproduce on the chip the known effects and toxicities of diclofenac and imatinib in people.
As published in Science Translational Medicine, they more than met the challenge. The researchers showed as expected that imatinib did not harm liver cells [1]. But, when treated with diclofenac, liver cells on the chip were reduced in number by about 30 percent, an observation consistent with the drug’s known liver toxicity profile.
As a second and more challenging test, the researchers reconfigured the BOC by placing a multi-drug resistant vulva cancer cell line in one chamber and, in another, a breast cancer cell line that responded to drug treatment. To explore side effects, the system also incorporated a chamber with human liver cells and two others containing beating human heart cells, along with devices to measure the cells’ electrical and mechanical activity separately.
These studies showed that tamoxifen, commonly used to treat breast cancer, indeed killed a significant number of the breast cancer cells on the BOC. But, it only did so after liver cells on the chip processed the tamoxifen to produce its more active metabolite! 
Meanwhile, tamoxifen alone didn’t affect the drug-resistant vulva cancer cells on the chip, whether or not liver cells were present. This type of cancer cell has previously been shown to pump the drug out through a specific channel. Studies on the chip showed that this form of drug resistance could be overcome by adding a second drug called verapamil, which blocks the channel.
Both tamoxifen alone and the combination treatment showed some off-target effects on heart cells. While the heart cells survived the treatment, they contracted more slowly and with less force. The encouraging news was that the heart cells bounced back from the tamoxifen-only treatment within three days. But when the drug-drug combination was tested, the cardiac cells did not recover their function during the same time period.
What makes advances like this especially important is that only 1 in 10 drug candidates entering human clinical trials ultimately receives approval from the Food and Drug Administration (FDA) [2]. Often, drug candidates fail because they prove toxic to the human brain, liver, kidneys, or other organs in ways that preclinical studies in animals didn’t predict. 
As BOCs are put to work in testing new drug candidates and especially treatment combinations, the hope is that we can do a better job of predicting early on which chemical compounds will prove safe and effective in humans. For those drug candidates that are ultimately doomed, “failing early” is key to reducing drug development costs. By culturing an individual patient’s cells in the chambers, BOCs also may be used to help doctors select the best treatment option for that particular patient. The ultimate goal is to accelerate the translation of basic discoveries into clinical breakthroughs. For more information about tissue chips, take a look at NIH’s Tissue Chip for Drug Screening program
[1] Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. McAleer CW, Long CJ, Elbrecht D, Sasserath T, Bridges LR, Rumsey JW, Martin C, Schnepper M, Wang Y, Schuler F, Roth AB, Funk C, Shuler ML, Hickman JJ. Sci Transl Med. 2019 Jun 19;11(497).
[2] Clinical development success rates for investigational drugs. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Nat Biotechnol. 2014 Jan;32(1):40-51

Tuesday, September 10, 2019

13th Annual Learning for Living Symposium: September 14th, 2019 Four Seasons Hotel Ballroom – 2nd Floor 200 Boylston Street, Boston

Don't forget to signup for the 13th Annual Learning for Living for September 14, 2019. 

WHEN: September 14th, 2019

WHERE: Four Seasons Hotel Ballroom – 2nd Floor
200 Boylston Street, Boston


It's sponsored by Ovations for the Cure and the line up of topics will be of interest to many.

It's FREE and women are encouraged to bring a guest. Parking is at a discount and there's always a wonderful breakfast and lunch. There's a great line-up of speakers covering many topics.

Some of the topics will include the latest update on PARP inhibitors, misconceptions about clinical trials, a Q&A session and a session on hospital vs network based patient centered care for advanced ovarian cancer. To sign up, follow this link.

Thursday, August 22, 2019

Ovarian Cancer's New Identity: A Chronic Disease

This article was originally posted CURE Today on April 1, 2019. Written by Deborah Abrams Kaplan
Women with this disease are living longer, despite common recurrence.
 When Luci Berardi received a stage 4 ovarian cancer diagnosis in October 2010, she did not want to know her chances of survival. The physician told her family she'd be lucky to make it through Christmas, but no one passed that on to her. "I knew I had cancer and needed chemotherapy. It was bad enough (that) I knew it was stage 4," Berardi says. She focused on her treatment and healing and revamped her diet, while still teaching yoga and working part time doing administrative work for a dental practice.
About 85 to 90 percent of ovarian cancers are epithelial cancer. For those with stage 4 disease, "the statistics may say that 17 to 20 percent will survive five years, but it's not zero," Berardi says. "People survive." Survival rates are higher for other ovarian cancers — for all types, the five-year relative survival is 47 percent. If the disease is found early and has not spread outside the ovary, that rate jumps to 92 percent.

Like Berardi, women are living longer with ovarian cancer, and it's increasingly seen as a chronic disease. Front-line, or initial, treatment hasn't changed much in the past decade. But in recent years, new treatments have been added to the mix. These include oral therapies instead of IV; combination, immuno- and anti-angiogenic therapies; and PARP inhibitors. Most of these are for recur­rent disease and may be based on genetic testing results. For the estimated 22,530 women a year who receive an ovarian cancer diagnosis in the United States, this is good news. Testing for genetic mutations may look at inherited mutations, which a person is born with, and show a higher likelihood of cancer risk. Genetic testing can also be done on the tumor tissue, showing genetic changes that were acquired later, and results may indicate whether specific treatments are more likely to help.
Luci Berardi says she views her disease no different than someone who has high blood pressure or diabetes.

About 75 percent of women with ovarian cancer receive their diagnosis when the disease is stage 3 or 4. "The majority of them can be treated with curative intent," says Pam Khosla, M.D., section chief of hematology and oncology at Sinai Health System in Chicago. That includes debulking surgery, in which surgeons remove as much as they can of the visible tumors and cancerous tissue. Microscopic cancer cells and cancerous tissue that can't be surgically removed are then treated with chemotherapy — typically, carboplatin and Taxol (paclitaxel).

Some doctors recommend surgery before the standard six cycles of chemotherapy, whereas others recommend three cycles, surgery and then three more cycles. Surgery may be the first step if the tumor is causing pain or physical issues, such as a bowel obstruction, or the physician is unsure whether cancer is causing the problems.
That was the case for Erica Roberts. In December 2015, she had abdominal cramping so severe, she thought her appendix was bursting. A trip to the emergency room and radiology imaging led the physician to believe she had an ovarian cyst. Only during the operation several weeks later did he realize she had stage 3A high-grade serous carci­noma, and he removed her ovaries and affected organs.

Not all patients are candidates for surgery — maybe the cancer is too extensive or the surgeon doesn't think enough diseased tissue can be removed. The patient would typically receive chemotherapy every three weeks — two weeks on, one week off — or weekly, depending on the oncologist. After three cycles (or nine weeks) of treat­ment, imaging is repeated and cancer antigen (CA) 125 — a protein found in the blood — is measured. A CA 125 blood test can indicate a rise in ovarian cancer growth and determine how well the patient is responding to chemo­therapy. If chemotherapy is working, patients who have not yet had surgery may be scheduled.
In June 2018, the Food and Drug Administration (FDA) approved Avastin (bevacizumab), a targeted therapy that belongs to a class of drugs called angiogenesis inhibitors, to use with chemotherapy and then alone for about a year, for women with stage 3 or 4 ovarian epithelial cancer that has been surgically removed. It was shown to increase the average amount of time before a recurrence. "To date, it hasn't led to improvement of overall survival, but it keeps the cancer in remission four months longer than not using it," says Ursula Matulonis, M.D., director of gynecologic oncology at the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston.

About 70 percent of women with ovarian cancer will face a recurrence, according to the Ovarian Cancer Research Alliance. However, recurrence also varies by stage of disease. Maintenance therapy can help prevent the cancer from returning after the completion of chemotherapy. Up until a few months ago, Lynparza (olaparib), a PARP inhibitor, was approved only for patients who had a recurrence. But in December 2018, the FDA approved the oral medication as a first-line maintenance treatment for women with BRCA inherited (familial) genetic mutations — BRCA1 and BRCA2 raise a person's risk of developing certain cancers, such as ovarian, breast and prostate — and advanced-stage disease. The drug targets an enzyme inside cancer cells to make it less likely that the cancer cell will repair itself, resulting in cell death. "It's shown impressive results," Matulonis says, with an increase of three years in progression-free survival compared with placebo.

Regardless of BRCA mutation status, PARP inhibitors were already approved as a maintenance strategy, says Maurie Markman, M.D., president of medicine and science and a medical oncologist with Cancer Treatment Centers of America in Philadelphia. The PARP inhibitor Rubraca (rucaparib) is approved for women with BRCA-positive advanced ovarian cancer who received multiple lines of chemotherapy treatment, and Zejula (niraparib) was approved after subsequent chemo­therapy, no matter the BRCA status.

Although chemotherapy is the standard initial treatment, it doesn't work for everyone. Diane Davis learned of her stage 2C ovarian cancer diagnosis in January 2017. After having 18 inches of her sigmoid colon removed because of tumor involvement, she began chemotherapy. Three cycles in, she felt just as bad as she had before surgery. Radiology studies showed that the cancer had grown back, spreading into her lymph nodes. "I was dumbfounded," she says. "No one ever says people don't make it through chemo."

Genetic testing revealed that her tumor was microsatellite instability high (MSI-H) — cancer cells that have a greater than normal number of genetic markers and respond well to immunotherapy. Although immunotherapy has not been highly successful with ovarian cancer, Keytruda (pembrolizumab) was approved in 2017 for adult and pediatric patients with unresectable or metastatic solid tumors identified as MSI-H, just at the time she needed it. Davis started the two-year treatment that June, and in August, a CT scan showed that the new tumor was gone and the lymph node tumors shrunk. "We all cried," Davis says. "My doctor said he'd never seen anything like it."
Genetic testing should be done on all patients at the start of treatment, Matulonis says. This often involves blood tests that look at hereditary mutations. "Right now, there are at least 11 implicated genes for high-risk transmis­sion," she says. She recommends including as many genes as possible in the testing panel, not just the BRCA mutations. A genetic panel also covers Lynch syndrome, an inherited condition that increases a person's risk of developing cancers such as colon, endometrial and ovarian and is linked to several gene alterations. Davis is living with Lynch syndrome. In addition to those that are inherited, mutations can also be acquired in the tumor.

Tumor assays can be used that may point to experimental therapies that attack the cancer's vulnerabilities.

Although genetic testing is now highly recommended, not all patients think to ask for it. "A lot of people in my local support group hadn't heard of it," Davis says. "It's important — not only knowing that you might have a genetic mutation that could give you other types of cancer but (also) to know (about) other treatments avail­able. If my doctor hadn't done testing on my tumor, I couldn't get immunotherapy, and I'd not be talking to you today."
Berardi also found genetic testing helpful. When she had a recurrence in 2014, her doctor recommended chemotherapy because she did well on it previously. She heard about genetic testing and sent a tissue sample from the baseball-size tumor the surgeon found during surgery. The genetic profile showed that the standard chemo­therapy would not work well for the tumor. Instead, her doctor gave her etoposide, a chemotherapy less commonly used in ovarian cancer. It put her in remission, with no evidence of disease.


Living with a chronic disease may affect a person physi­cally and mentally. For instance, chemotherapy-related fatigue and nausea are common. Women with ovarian cancer also face sexual health concerns, such as painful sex, libido loss, early menopause and infertility. All these symptoms can lead to mental health issues such as depression and anxiety.
Through palliative care, health care providers can help patients through these concerns and improve their quality of life. "Palliative care doesn't mean hospice," Markman says. "'Palliate' means 'to improve, to make better.'" He prefers the term "supportive care." The goal of palliative care is to prevent or treat the symptoms of the disease as early as possible, according to the National Cancer Institute.

Patients within Sinai Health System meet with a multidisciplinary team, including a pharmacist, supportive oncology coordinator, nurse navigator and behavioral therapist, to schedule care, answer questions and address any issues, Khosla explains. Using this team approach has both improved patient satisfaction and quality of life and reduced hospital visits. Some hospitals reserve the palliative care specialists for those whose lives are heavily affected by treatment, though nurses and oncologists are trained to help with symptoms. "If you're feeling side effects, chances are they have something to help you get better," Roberts says of her oncology nurses. "You don't get a gold medal for going through chemo without taking pain pills."

Receiving palliative care can improve more than how a person feels, according to a study published in Annals of Behavioral Medicine, which showed that it can keep patients alive longer. Researchers analyzed studies that compared patients with advanced cancer who received palliative care with those who didn't. They found that the palliative care group lived 4.5 months longer.

As many as 20 percent of patients with advanced stage disease have no recurrence after front-line therapy. Still, life after treatment doesn't necessarily bring a sense of relief, especially when it's time for periodic CA 125 testing.

Roberts finished her front-line treatment in 2016, including surgery and IV and intraperitoneal chemo­therapy. She's been in remission since. "The closer I get to the three-month checkup, the drumbeat gets louder," and she thinks about the cancer constantly, she says. In addition to taking medications to handle her anxiety, she sees a counselor and goes to a Gilda's Club support group. "The physical scars are just about healed. The emotional footprints are left," she says.

Although difficult, the treatment process can still make women feel tended to. Once chemotherapy finished, Carol Hyman felt a cloud hanging over her — she felt alone and concerned about recurrence. "Even though the chemo is terrible, you're being taken care of; you're checked on continuously," she says. Hyman received a stage 3B diagnosis when she was 65. Physicians found three large tumors and removed about a dozen lymph nodes.
In addition to finding her own support network, Berardi changed her diet. She sees a naturopath to get high-dose vitamin C infusions and supplements to reduce inflammation. She eliminated processed sugar and dairy and decreased her intake of carbohydrates. She takes a small amount of naltrexone and metformin, prescribed by her naturopath, in hopes of preventing recurrence. Patients sometimes use naltrexone at low doses to inhibit cancer growth and balance the immune system. Metformin targets stromal inflam­mation, which may provide resistance to cancer growth. Neither is approved by the FDA for ovarian cancer treatment because of lack of clear proof from controlled clinical trials, but anecdotal evidence suggests that some patients may benefit from these medications. "I'm trying to create an internal environment that is not conducive for the cancer to survive," Berardi says.

Although she has had two recurrences, she says, the experience was in a way a blessing. "It took some of the anxiety away," Berardi says. "My mindset now is that it's a chronic disease, nothing different than high blood pressure or diabetes. You have to monitor it." She also wrote a book, "Chasing Rainbows: My Triumph Over Ovarian Cancer," because she was unable to find that sort of resource when she first received her diagnosis.

Hyman also finds support groups comforting. At her first meeting, she realized that every woman there had had at least one recurrence. Even though that talk can be scary, Hyman says, it gave her hope. One woman's comment left a lasting impact: "I'm not dying from ovarian cancer — I'm living with ovarian cancer."

Wednesday, August 21, 2019

Donna Wiegle: Leaving on her Cross-Country Trip To Raise OC Awareness

August 18, 2019by Donna WiegleOrganizer

Just 9 days left until I depart for Coos Bay, Oregon. Last I heard my bike had made it as far as Columbus, OH, expecting to be delivered at Highway 101 Harley Davidson on August 23. I arrive on August 27 and if all goes well on my travels across the country I will begin my ride the following day.

My fundraising is going amazingly well!!! I am just $91 short of $28,000!!!! It is unbelievable how generous both people I know, and those I don't know have been! It's so heartwarming to have so many people supporting me and my mission.

Speaking of support, you can see from my picture here that I am sporting my new black leather vest with my TEAL on WHEELS patch on the back. A lovely lady from Cherryfield, Downeast Maine, sewed the patch on for me and would't accept any payment! I had the same thing happen when Les Foss inspected my teal and white money exchanged hands. Also, when I got the bike serviced by Stanley Gardner at Gardner Racing Concepts...Stanley provided all the parts and labor free of charge to support me.  

It's crunch time now and I still have a long list of things to do, but each day I am making progress towards my departure date. I am excited, nervous, and just a little bit scared! I know everything will work out just fine. I packed 1,000 ovarian cancer symptoms cards rubberbanded in packs of 25, then packed in ziplock bags in my saddlebags of my bike. I hope to distribute every last one on my way across the United States.

If you want to follow my trip, go to and subscribe to my blog on the bottom of the home page. I will be posting frequently from the road.

Thank you for all of your support. It means the world to me!

To donate to Donna's campaign to raise awareness about the signs and symptoms of ovarian cancer, go to this link