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  
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
508-655-5412

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. 

ChemoWave
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 ChocolateCoveredKatie.com

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.)