Tuesday, June 21, 2022

Rucaparib Maintenance Shows PFS Benefit in Ovarian Cancer, Independent of HRD Status

 This is an edited version of an article by Ariana Pelosi published in OncLive June 6, 2022.

Rucaparib elicited a significant improvement in progression-free survival outcomes vs placebo as first-line maintenance therapy in patients with ovarian cancer who responded to first-line platinum-based chemotherapy across patient subgroups.

Rucaparib (Rubraca) elicited a significant improvement in progression-free survival (PFS) outcomes vs placebo as first-line maintenance therapy in patients with ovarian cancer who responded to first-line platinum-based chemotherapy across patient subgroups in both the primary and exploratory analyses of the ATHENA-MONO trial (NCT03522246). Specifically, the PARP inhibitor demonstrated improvements in both homologous recombination deficient (HRD)-positive and HRD-negative populations, findings from which were presented at the 2022 ASCO Annual Meeting....

“Patients with measurable disease at baseline have further tumor reduction with rucaparib. [Additionally], rucaparib safety profile is consistent with prior studies,” Bradley J. Monk, MD, FACS, FACOG, professor in the Division of Gynecologic Oncology at the University of Arizona College of Medicine, medical director of the Gynecologic Program at US Oncology Research Network, and lead investigator of this study, said during the presentation.

Friday, June 17, 2022

A Sensor Sniffs for Cancer, Using Artificial Intelligence

This is an edited version of an article  published on the Clearity Foundation website on May 12, 2022.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have developed a sensor that can be trained to sniff for cancer, with the help of artificial intelligence.

Although the training doesn’t work the same way one trains a police dog to sniff for explosives or drugs, the sensor has some similarity to how the nose works. The nose can detect more than a trillion different scents, even though it has just a few hundred types of olfactory receptors. The pattern of which odor molecules bind to which receptors creates a kind of molecular signature that the brain uses to recognize a scent.

Like the nose, the cancer detection technology uses an array of multiple sensors to detect a molecular signature of the disease. Instead of the signals going to the brain, they are interpreted by machine learning — a type of computer artificial intelligence.

MSK researchers led by Kravis WiSE Postdoctoral Fellow Mijin Kim and biomedical engineer Daniel Heller, head of the Cancer Nanomedicine Laboratory at MSK, built the technology using an array of sensors composed of carbon nanotubes. Carbon nanotubes are tiny tubes, nearly 100,000 times smaller than the width of a human hair. They are fluorescent, and the light they give off is very sensitive to minute interactions with molecules in their environment.

Each nanotube sensor can detect many different molecules in a blood sample. By combining the many responses of the sensors, the technology creates a unique fluorescent pattern. The pattern can then be recognized by a machine-learning algorithm that has been trained to identify the difference between a cancer fingerprint and a normal one.

In experiments conducted on blood samples obtained from patients with ovarian cancer, the researchers found that their nanosensor detected ovarian cancer more accurately than currently available biomarker tests. (A biomarker is a particular chemical produced by tumors and spread through the blood circulation that indicates the presence of disease. In this case, the biomarker tests were ones for the ovarian cancer-related proteins CA125, HE4, and YKL40.)

The hope for patients is that researchers will develop the technology further so that it can eventually be used in the clinic to rapidly screen for early-stage ovarian cancer and many other cancers.

Need for Better Cancer Screening Tests

Tests that detect early-stage cancers using blood markers hold great promise for improving outcomes for people with cancer — especially those types, like ovarian cancer, that have few early signs or symptoms.

Several serum biomarker tests for ovarian cancer are already in use. Unfortunately, these standalone biomarker measurements have proven to be ineffective at early detection. Currently, no screening strategy can identify ovarian cancer at an early enough stage to reduce mortality.

The nanosensor approach could potentially provide a better way.

“Ovarian cancer spreads along the surfaces of the abdomen and pelvis [as opposed to through the blood], which makes finding it with a blood test especially challenging,” says MSK surgeon Kara Long Roche, who was an author on the study. “This technology could potentially find more subtle, complex changes in the blood, which may be the key to early detection — and early detection will save lives.”

To train the machine-learning algorithm, the researchers needed to collect sensor responses from many blood samples, as this method requires many examples to be accurate. In addition, samples from patients with other conditions besides ovarian cancer were used: “Certain other diseases can trick the sensor because they produce some of the same components in the blood,” says Dr. Kim, the lead author of the study.

Although the technology improves the accuracy of ovarian cancer detection over current biomarker-based methods, more work is needed to enable the detection of early-stage ovarian cancer and confirm that this test works in people.

“We won’t stop until there is a way to prevent ovarian cancer deaths,” says Dr. Heller.

Sunday, June 12, 2022

Investigators Hope Oregovomab Will Show Benefit in Advanced Epithelial Ovarian Cancer

 This is an edited version of an article  written by Lindsay Fischer and published by the Clearity Foundation

A new murine monoclonal antibody B43.12 is under investigation in combination with paclitaxel and carboplatin as a treatment option for patients with advanced epithelial ovarian cancer.

Oregovomab (Ovarex) in combination with paclitaxel and carboplatin for patients with advanced epithelial ovarian cancer is being tested in the phase 3 FLORA-5 trial (NCT04498117). Oregovomab is an investigational monoclonal antibody with promising phase 2 data. Oregovomab and the FLORA-5 trial were highlighted during the 2022 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in March.

“Oregovomab is an investigational monoclonal antibody that has been studied in clinical trials for patients with ovarian cancer whose tumor cells express the tumor-associated antigen CA-125 (MUC16),” the investigators noted in a poster presentation during the meeting. “Oregovomab is a novel immunotherapy that enhances the immune response to CA-125.”

The phase 3 double-blind, placebo-controlled, multicenter study has been designed to compare the safety and efficacy of oregovomab plus chemotherapy with placebo plus chemotherapy. Patients will be randomly assigned 1:1 to receive either 2 mg of intravenous oregovomab or placebo, along with 6 standard cycles of paclitaxel/carboplatin.

Additionally, investigators will seek to confirm the clinical benefit observed in a randomized phase 2 study (NCT01616303), which demonstrated that adding oregovomab to paclitaxel and carboplatin resulted in clinically significant improvements in progression-free survival (PFS) and overall survival (OS).

Investigators noted that the trial will also seek to evaluate the role of oregovomab as a neoadjuvant chemotherapy option.


Endometriosis and ovarian cancer genetically tied

 This article is taken from ScienceDaily, March 15, 2022

University of Queensland researchers have demonstrated a genetic link between endometriosis and ovarian cancer subtypes enabling them to identify potential drug targets for therapy and increasing the understanding of both diseases.

Previous studies have shown that endometriosis sufferers have a slightly increased risk of developing epithelial ovarian cancer.

Dr Sally Mortlock and Professor Grant Montgomery from UQ's Institute for Molecular Bioscience carried out a large genetic study to identify a genetic basis for this risk with a view to better understand the biological overlap between these reproductive disorders.

"More information about how they develop, their associated risk factors, and the pathways shared between endometriosis and different types of ovarian cancer has been needed," Dr Mortlock said.

Endometriosis is a chronic debilitating disease that affects the health of 1 in 9 women of reproductive age, where tissue similar to the uterus lining grows in other parts of the body, causing pain and infertility.

"Our research shows that individuals carrying certain genetic markers that predispose them to having endometriosis also have a higher risk of certain epithelial ovarian cancer subtypes, namely clear cell and endometrioid ovarian cancer."

Dr Mortlock said that although the diseases are genetically linked, the risk of ovarian cancer for those with endometriosis is not substantially increased.

"Overall, studies have estimated that 1 in 76 women are at risk of developing ovarian cancer in their lifetime and having endometriosis increases this slightly to 1 in 55, so the overall risk is still very low," she said.

The study found genes that could be drug targets to treat both endometriosis and epithelial ovarian cancer in the future.

"We explored specific areas of DNA that increase the risk of both diseases and identified genes in ovary and uterus tissue that could be targets for therapy and may be valuable to understand the link between the disorders and to disrupt biological pathways initiating cancer."

The researchers combined large datasets comparing the genomes of 15,000 people with endometriosis and 25,000 with ovarian cancer to find an overlap in risk factors between the two diseases.

The collaboration also involved Associate Professor Kate Lawrenson at Cedars-Sinai Medical Center and Dr Siddhartha P. Kar from the University of Bristol.

Tuesday, May 10, 2022

FDA Grants Fast Track Designation to VB-111 for Platinum-Resistant Ovarian Cancer

This is excerpted from an article in OncLive by Chris Ryan April 22, 2022
The FDA has granted a fast track designation to VB-111 (ofranergene obadenovec), a targeted anticancer viral gene therapy, for use as a potential therapeutic option in patients with platinum-resistant ovarian cancer.
    VB-111 is designed to use a dual mechanism to target a wide range of solid tumors, including ovarian cancer. The mechanism pairs the blockade of tumor vasculature with an antitumor immune response. Prior data from a phase 1/2 trial (NCT01711970) indicated that when VB-111 was combined with paclitaxel in this patient population, it was efficacious and safe.
    Among the 21 patients enrolled to the trial, approximately half had platinum-refractory disease and half previously received treatment with antiangiogenics....
The combination is currently under further exploration in the phase 3 OVAL trial (NCT03398655), where it is being compared with paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer.
    “We are pleased to receive FDA fast track designation for [VB-111] in platinum-resistant ovarian cancer. The fast track designation can facilitate the process toward potential registration and, importantly, may help expedite the time to market for [VB-111], if approved,” Dror Harats, MD, chief executive officer of VBL Therapeutics, stated in a press release. “The readout of the PFS primary end point in the OVAL trial will be an important milestone for VBL in the second half of [2022]. We believe that, if positive, this will support a biologics license application submission to the FDA.”
OVAL recently completely enrollment of 409 patients, and the trial is being conducted at cancer centers throughout the United States, Europe, Israel, and Japan. 

Friday, May 6, 2022

2022 TTT Retreat Applications/Forms


This year our annual Turning the Tide Ovarian Cancer Retreat will be held at beautiful, Essex Woods Meeting and Retreat Center, in Essex, MA.

The links are available at the bottom of the screen for you to download the application instructions, the application itself, the health history form and the consent form. You can print it out and send it back to me via email or mail. If you have trouble opening the link or you are without the ability to print, please contact me at mastrangelom@comcast.net so that I can send you a hard copy.

The acceptance process is not first-come, first-serve. Please make sure that if you are mailing the hard copy of your forms, it must be received by Tuesday, May 24th so that we can contact you by Friday, May 27th by email or 'phone to confirm your spot. We will have a wait list available.

Do not send any payment at this time - please wait until your spot has been confirmed.

·      Again, only after you have been notified of your spot, please send your check for $250 (or any amount – we want all women to attend regardless of ability to pay) payable to: Turning the Tide Ovarian Cancer Retreats Inc.

 NOTE: If you need to request a scholarship (assistance for payment) please check the box on the application form.

We so look forward to your application! 

Here are the links to each document:

Application Instruction

Application

Health Form

Consent Form



Monday, April 11, 2022

Online tool helps ovarian cancer patients feel more in control of symptoms

This is an edited version of an article published on ScienceDaily February 8, 2022.

An online symptom management tool that harnesses the problem-solving benefits of expressive writing could help women with ovarian cancer better manage complex symptoms, according to a new study led by a University of Pittsburgh and UPMC nurse-scientist.

Published in the Journal of Clinical Oncology, the study found that patients who used nurse-led and self-directed versions of the tool reported a better sense of control over symptoms compared to enhanced usual care.

"Women with ovarian cancer experience an average of 14 concurrent symptoms, so symptom management is very complex. It can be overwhelming for patients and challenging for providers, who may not have time to address these symptoms in a typical 15-minute appointment," said lead author Heidi Donovan, Ph.D., R.N., professor of health and community systems in Pitt's School of Nursing and obstetrics, gynecology and reproductive services in the School of Medicine. "That's why we developed a symptom management approach outside of a normal clinical setting, from the comfort of a woman's own home."

According to Donovan, ovarian cancer is a "low incidence, high impact cancer." In 2022, about 20,000 women will be diagnosed with ovarian cancer in the U.S., and more than 12,000 will die. For many patients who are treated successfully, the cancer recurs after two to three years.

"There's a vast difference in quality of life between patients who manage symptoms successfully and those who don't, both throughout chemotherapy and afterwards," said Donovan, who is also director of the Gynecologic Oncology Family CARE Center at UPMC Magee-Womens Hospital. "Effective symptom management requires that patients follow directions from providers but also be willing to communicate, make adjustments and try new strategies."

Donovan and her team developed a new symptom management approach called Written Representational Intervention to Ease Symptoms, or WRITE Symptoms, which guides patients to reflect on how they experience a symptom: what causes it, what makes it worse, how it feels, how it impacts their daily life and how they've tried to manage it.

"The WRITE approach blends health psychology with educational principles," explained Donovan. "The process of talking or writing about a symptom in a systematic way can help women understand which management strategies work and which don't. Using evidence-based symptom management techniques, we then help patients develop strategies for addressing target symptoms. Later, patients review the strategies and assess if changes need to be made. It's a very iterative process."

The researchers recruited 497 patients with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer. After participants completed surveys about symptom burden, controllability and quality of life and selected three target symptoms they wanted better control of, they were randomly assigned to one of three groups.

One group completed a nurse-led version of the WRITE intervention, in which nurses guided patients through the process via an asynchronous web-based message board. The second group directed themselves through a fully computer-mediated version of WRITE. The third, or enhanced usual care group, did not complete WRITE and acted as a control.

The analysis found that both WRITE interventions improved women's sense of control over their symptoms after eight weeks, and these measures were significantly greater compared with enhanced usual care.

"To see the same benefits in both the nurse-led and fully computer-mediated versions of the program is really powerful," said Donovan. "We also found that the self-led program was much more efficient: People were able to develop a symptom management plan in about 30 minutes compared to a few weeks with the asynchronous, nurse-led version."

The researchers are now developing a mobile health app that will train family members and other caregivers to help their loved ones with ovarian cancers better manage symptoms. Based on the computer-mediated version of WRITE, the app will guide users through questionnaires and problem-solving exercises, and it will feature disease-specific modules and core modules that could apply to patients with any chronic disease. For patients who need extra support, there will also be an option to connect with providers. According to Donovan, this app could be offered to families of gynecology cancer outpatients in the next year or so.


Story Source:

Materials provided by University of PittsburghNote: Content may be edited for style and length.


Thursday, April 7, 2022

Conjugate Therapy Produces Remissions in One-Third of Patients with Drug-Resistant Ovarian Cancer, Study Results Show

This is a news release from Dana Farber Cancer Institute, published on March 19, 2022

In a clinical trial involving patients with ovarian cancer previously treated with platinum-based chemotherapy, a novel “conjugate” therapy produced a substantially better response than standard treatments, investigators at Dana-Farber Cancer Institute...

The agent, mirvetuximab soravtansine, generated an objective response – a measurable decrease in cancer burden – in nearly 33% of patients participating in the trial. That compares with response rates in the single digits for current treatments in patients whose ovarian cancer doesn’t respond to platinum-based chemotherapy.

The novel agent is one of a growing number of antibody-drug conjugates, or ADCs, which consist of a drug linked to an antibody that directly targets the cancer cell. Mirvetuximab connects an antibody targeting the folate receptor alpha molecule on high-grade serous ovarian cancers to a drug molecule called DM4 that disrupts microtubule formation. (Microtubules are major components of the cytoskeleton that give shape and structure to cells.) The folate receptor protein is far more abundant in some tumor cells than normal cells, making it an attractive target for cancer drugs.

The trial, titled the SORAYA study, enrolled 106 patients with platinum-resistant high-grade serous ovarian cancer that highly expressed folate receptor alpha. All patients were required to have previously received bevacizumab, a drug that blocks tumors from forming blood vessels to take in more oxygen and nutrients. The participants had been treated with up to three prior treatments for their ovarian cancer.

After a median follow-up of 8.1 months, 32.4% of participants had an objective anti-cancer response, including five who had a complete response, or the disappearance of all signs of cancer. The median duration of response is currently 6.9 months.

Mirvetuximab was well-tolerated by study participants. The most common adverse side effects associated with the treatment were blurred vision, keratopathy (a non-inflammatory condition of the eye), and nausea.

“These data have the potential to be transformative for ovarian cancer patients and their physicians,” said Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at Dana-Farber and co-principal investigator of the SORAYA study, who will present the findings at the SGO. “In the platinum- resistant setting and particularly in later-line treated patients, response rates with available therapy are in the single digits with significant toxicities. With an objective response rate above 30%, a duration of response of around six months, and a treatment-related discontinuation rate of 7%, mirvetuximab shows impressive activity and tolerability for patients with platinum-resistant ovarian cancer.  These data support the future of mirvetuximab as the potential standard of care for patients with folate receptor alpha positive ovarian cancer.” 

Monday, April 4, 2022

Niraparib Plus Bevacizumab Shows Promise in High-Risk Ovarian Cancer Population

 This is a shortened version of an article written by Kyle Doherty and published in OncLive March 19, 2022


Niraparib (Zejula) in combination with bevacizumab (Avastin) was efficacious following 1 line of platinum-based chemotherapy among patients with newly diagnosed advanced ovarian cancer regardless of biomarker status, according to data from an updated analysis of the phase 2 OVARIO study (NCT03326193) presented during the 2022 SGO Annual Meeting on Women’s Cancer.

Melissa Hardesty, MD, MPH, added that combination had a safety profile consistent with the known adverse effects of each treatment as monotherapy.

At the June 16, 2021, data cutoff point, patients who received the PARP inhibitor niraparib plus the vascular endothelial growth factor-A inhibitor bevacizumab (N = 105) achieved a median progression-free survival (PFS) of 19.6 months (95% CI, 16.5-25.1). The 18-month PFS rate was 62% (95% CI, 52%-71%) and the 24-month PFS rate was 53% (95% CI, 43%-63%). Median follow-up was 28.7 months (interquartile range, 23.9-32.5).

“OVARIO enrolled a high-risk population,” said Hardesty, a gynecologic oncologist with Alaska Women’s Cancer Care in Anchorage. “More than half of the patients remained progression-free at 24 months. Clinical benefit [by PFS] was observed in the overall population, and across biomarker subgroups in a continuum.”

Wednesday, March 30, 2022

INNOVATE-3 Trial Examining Tumor Treating Fields in Platinum-Resistant Ovarian Cancer Recommended to Continue

This is a shortened version of an article written by Kristi Rosa and published in OncLive March 24, 2022

An independent data monitoring committee (DMC) has recommended that the phase 3 INNOVATE-3 trial  exploring the safety and efficacy of tumor treating fields (TTFields) in combination with paclitaxel in patients with platinum-resistant ovarian cancer proceed to the final analysis, according to an announcement from Novocure.

The recommendation follows a review of safety findings for all the patients enrolled to the trial, and an analysis of overall survival (OS) that was done on the first 540 patients who underwent randomization. Data from the prespecified interim analysis of the trial did not signal for a need to increase the sample size, and so the trial will continue as planned.

“Completion of the DMC interim analysis represents the next milestone in our journey to address the significant unmet need for patients diagnosed with platinum-resistant ovarian cancer,” Ely Benaim, MD, chief medical officer of Novocure, stated in a press release. “I would like to thank our investigators and collaborators, ENGOT and The GOG Foundation, as well as our patients for their passion and bravery. We look forward to reviewing final data next year.”

TTFields are electric fields that disturb cancer cell division. These fields can hinder electrically charged cellular components of cancer cells and disrupt their function, which could result in cell death. With this approach, cancer cell division can either be slowed down or stopped. Utilizing the investigational medical device referred to as NovoTTF-200(O), the fields are delivered to the region of the body where the tumor is located. [Learn more about TTFields here]

The pivotal, open-label, phase 3 INNOVATE trial enrolled patients with a histologically confirmed diagnosis of ovarian carcinoma that has been unresponsive to therapy containing platinum within 6 months of their last treatment, who are at least 18 years of age and have a life expectancy of at least 12 weeks. Patients needed to be amenable to receive weekly paclitaxel and be able to operate the NovoTTF-200(O) device.

Study participants were randomized to receive either weekly paclitaxel alone or weekly paclitaxel concomitantly with TTFields tuned to 200 kHz until disease progression.

The primary end point of the trial is OS [overall survival], and key secondary end points include progression-free survival (PFS), objective response rate, severity and frequency of adverse effects, time to deterioration in health-related quality of life (QOL) or death, and QOL.

As of October 2021, the study has accrued a total of 540 patients. Data from the trial are anticipated to be reviewed in 2023, after an 18-month follow-up period.

Previously, TTFields in combination with weekly paclitaxel was observed in patients with platinum-resistant ovarian cancer as part of the single-arm, phase 2 INNOVATE trial (NCT02244502).

Friday, March 18, 2022

Ovations for the Cure of Ovarian Cancer Fundraising Event

 Let's Support Our Sister Organization:

Image


JOIN US AT PUTTS & MORE FOR FUN AND FUNDRAISING!

 

MAY 21, 2022 1OAM TO 2PM

750 Concord Street, Holliston, MA

 

18 HOLE MINI GOLF

  $15 PER PERSON (AGES 9 and up)

$10 PER PERSON (AGES 3 -8)

 

NO PRESALES - PAY AT THE GOLF COURSE!

 

PLAY GOLF, VISIT WITH FRIENDS, ENJOY A SNACK FROM THE SNACK BAR AND HELP SUPPORT OUR PATIENT PROGRAMS.

 

Picnic table area also available

 

For more info on Putts and More, please visit

https://puttsandmore.com/

For more information contact:  susan@ovationsforthecure.org 

 



 Ashton Thompson becomes the first National Ovarian Cancer Coalition (NOCC) Athletic Ambassador, committed to spreading awareness on and off the track

From the National Ovarian Cancer Coalition, story copied from EINPresswire:

DALLAS, TX, UNITED STATES, March 8, 2022 /EINPresswire.com/ -- 1 in 78 - no, that’s not the ratio of female to male drivers in the racing world, that is a woman’s risk of getting ovarian cancer in her lifetime. Kenyon Midget race fans will spend the 2022 season learning about the risks, signs, and symptoms of ovarian cancer thanks to the NOCC’s first Athletic Ambassador, Ashton Thompson. “After looking into the NOCC, I quickly realized that this partnership would be a huge success. I want to do everything I can to spread awareness for ovarian cancer and be here to support anyone who has to endure this horrible disease.”

As an Athletic Ambassador for the organization, Thompson will support early awareness and education initiatives in a sport with plenty of female fans, but few female drivers to look up to. As the only female driver in the field this race season, Thompson’s unique perspective and passion for racing will inspire women across the country to take action and advocate for their health. "We are proud to have Ashton join us in bringing much-needed awareness to ovarian cancer,” shared NOCC CEO Melissa Aucoin, “ a disease that impacts over 21,000 women in the U.S each year, and so grateful to have her heroic commitment in reaching and empowering new audiences of women everywhere with lifesaving health messages."

NOCC and Ashton Thompson Racing are excited to partner during the 2022 race season to break barriers on the track and break the silence on ovarian cancer. To learn more about the 2022 Kenyon Midget Race Season and where you can catch Ashton, visit ashtonthompsonracing.org.



Friday, March 11, 2022

Study in Finland Reveals How Ovarian Cancer Cells Hide from the Immune System

This article is taken from ScienceDaily

Every year, roughly 550 women develop ovarian cancer in Finland. Ovarian cancer is difficult to treat and it is commonly fatal, with 320 women dying of ovarian cancer annually in Finland.

Cancer can only develop and progress when the tumor cells are able to hide from the body's immune system. Cancer immunotherapies, which boost the body's immune defense against cancer, have emerged as promising therapies in multiple tumor types. However, the effectiveness of immunotherapies against ovarian cancer has remained modest. This is mainly since the mechanisms how ovarian cancer cells hide from the immune system have been unknown.

Now, researchers at the University of Helsinki have uncovered how tumor cells interact with the immune system in ovarian cancer. Utilizing a novel imaging technology, the researchers characterized more than 110,000 individual cells from clinical ovarian cancer samples. The researchers investigated how the genetic characteristics of ovarian cancer the shape human immune system, and how tumor and immune cells communicate with each other.

"With the help of this revolutionary imaging technology and advanced data analysis, we were able to study individual tumor cells, their functional properties and interactions with unprecedented precision," says Associate professor Anniina Färkkilä, the corresponding author of the study.

Tumor genes trick the immune system

"By studying individual cells directly in the tissue, we demonstrated how cancer cells hide in different ways, depending on the specific gene mutation. We found that the body's immune system is more effective against tumors with a mutation in BRCA1/2 genes. By contrast, tumors without such mutations have a connective tissue barrier prohibiting the interaction between the cancer and immune cells," says doctoral researcher Inga-Maria Launonen, BM.

BRCA1/2 mutations occur in approximately 20% of poorly differentiated serous carcinomas, the most common form of ovarian cancer. The killer T-cells closely guarded the aggressive tumor cells particularly in tumors with BRCA1/2 mutations, which is why these patients had a markedly better prognosis.

"By increasing our understanding of how tumor genes trick the immune system, we will be able to develop more effective ways to activate the body's own immune defenses to kill the cancer cells," Inga-Maria says.

Results will promote the tailoring of precision therapies

The results of the study confirm the significance of the interaction between tumor and immune cells in identifying new and more effective therapies as well as in choosing the right therapy for each patient.

"Our findings will enable us to tailor precision immuno- and combination therapies that have the potential to even cure ovarian cancer in the future," Färkkilä says.


Thursday, March 10, 2022

Six Day Treatment Eradicates Advanced OC and Colorectal Cancer in 100% of Animals


(This article was written by Jade Boyd from Rice University's Office of Public Affairs.)
Bioengineers have shown they can eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days with a treatment that could be ready for human clinical trials later this year.

The treatment and animal test results are described online today in a Science Advances study co-authored by Omid Veiseh, Amanda Nash and colleagues from Rice, the University of Texas MD Anderson Cancer Center, the University of Virginia and others.

Veiseh, an assistant professor of bioengineering whose lab produced the treatment, said human clinical trials could begin as soon as this fall because one of his team’s key design criteria was helping cancer patients as quickly as possible. The team chose only components that had previously proven safe for use in humans, and it has demonstrated the safety of the new treatment in multiple tests.

“We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated,” Veiseh said. “Once we determined the correct dose — how many factories we needed — we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer.”

In the newly published study, researchers placed drug-producing beads beside tumors and within the peritoneum, a sac-like lining that supports intestines, ovaries and other abdominal organs. Placement within this cavity concentrated interleukin-2 within tumors and limited exposure elsewhere.

“A major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” said study co-author Dr. Amir Jazaeri, professor of gynecologic oncology and reproductive medicine at MD Anderson. “In this study, we demonstrated that the ‘drug factories’ allow regulatable local administration of interleukin-2 and eradication of tumor in several mouse models, which is very exciting. This provides a strong rationale for clinical testing.”

Interleukin-2 is a cytokine, a protein the immune system uses to recognize and fight disease. It is an FDA-approved cancer treatment, but Nash, a graduate student in Veiseh’s group and the study’s lead author, said the drug factories provoke a stronger immune response than existing interleukin-2 treatment regimens because the beads deliver higher concentrations of the protein directly to tumors.

“If you gave the same concentration of the protein through an IV pump, it would be extremely toxic,” Nash said. “With the drug factories, the concentration we see elsewhere in the body, away from the tumor site, is actually lower than what patients have to tolerate with IV treatments. The high concentration is only at the tumor site.”Nash said the same general approach used in the study could be applied to treat cancers of the pancreas, liver, lungs and other organs. The drug factories could be placed next to tumors and within the linings that surround those organs and most others, she said. And if a different cytokine is needed to target a specific form of cancer, the beads can be loaded with engineered cells that make that immunotherapeutic compound.

The bead’s outer shell shields its cytokine-producing cells from immune attacks. The shells are made of materials the immune system recognizes as foreign objects but not as immediate threats, and Veiseh’s lab leveraged that in its design.

“We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days,” he said. “We also showed we could safely administer a second course of treatment should it become necessary in the clinic.”

Avenge Bio , a Massachusetts-based startup co-founded by Veiseh, has licensed the cytokine-factory technology from Rice.

Additional co-authors include Maria Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrea Hernandez, Andrew Hecht, Yufei Cui, Shirin Nouraein, Jared Lee, David Zhang and Oleg Igoshin of Rice; Peter Rios, Sofia Ghani, Ira Joshi and Douglas Isa of CellTrans Inc.; Chunyu Xu and Weiyi Peng of the University of Houston; Rahul Sheth of MD Anderson; and José Oberholzer of both CellTrans Inc. and the University of Virginia.

The research was funded by the Cancer Prevention Research Institute of Texas (RR160047), Avenge Bio, the Emerson Collective, the Welch Foundation, the Rice University Academy of Fellows, the National Science Foundation (1842494) and the National Institutes of Health (R01DK120459).
Jazaeri receives compensation as a consultant on Avenge Bio’s scientific advisory board and has disclosed the relationship to MD Anderson in accordance with its conflict-of-interest policy. Nash, Jarvis, Aghlara-Fotovat, Mukherjee, Hecht, Igoshin, Zhang and Veiseh declared interests via patents filed by Rice on the cytokine factories. Igoshin, Veiseh and Oberholzer are paid consultants for Avenge Bio. Nash, Zhang, Sheth, Oberholzer, Jazaeri and Veiseh hold equity in Avenge Bio.

Wednesday, March 9, 2022

New drug combination effective for patients with advanced ovarian cancer

 This article is taken from ScienceDaily.

A new study led by researchers at Yale Cancer Center and the University of Maryland Comprehensive Cancer Center shows ixabepilone plus bevacizumab (IXA+BEV) is a well-tolerated, effective combination for treatment of platinum/taxane-resistant ovarian cancer compared to ixabepilone (IXA) alone. The data shows it also may significantly extend both progression free survival and overall survival. The results were published in the British Journal of Cancer.

"Novel approaches for relapsed ovarian cancer are desperately needed as limited effective combinations currently exist to treat our patients. The results of this study demonstrated a drug combination that may be an effective treatment for this type of ovarian cancer," said Alessandro Santin, MD, Professor of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine and Disease Aligned Research Team Leader for the Gynecological Cancers Program at Yale Cancer Center and Smilow Cancer Hospital and senior author of the study.

Ovarian cancer is the most lethal gynecologic malignancy. According to the American Cancer Society, nearly 20,000 women will be diagnosed with ovarian cancer in the United States every year, and more than 12,000 women will die from the disease. IXA is a microtubule-stabilizing agent that may be beneficial in patients treated with platinum/paclitaxel. Bevacizumab (BEV) is an antibody that keeps new blood vessels from forming and has shown clinical activity in ovarian cancer.

In this phase II study, researchers randomly assigned 78 patients to receive IXA+BEV or IXA alone. The primary endpoint was progression-free survival (PFS), Overall survival (OS), safety, and response rates served as secondary endpoints. Researchers also examined whether the presence of the protein TUBB3 within the tumor could predict clinical response to these drugs. Among 76 evaluable patients who received IXA+BEV compared to IXA, the response rate was 33% versus 8%, with clinical benefit durable at 6 months in 37% and 3%. The addition of BEV significantly improved both PFS (5.5 months vs 2.2 months) and OS (10 months vs 6 months). Both regimens were well-tolerated.

"We expect our findings to have major implications in the field of gynecologic oncology since they add a new, effective treatment for these extremely challenging tumors for which there are otherwise few options," said first author Dana M. Roque, MD, Associate Professor of the Division of Gynecologic Oncology at the University of Maryland School of Medicine and member of the Marlene & Stewart Greenebaum Comprehensive Cancer Center.

This article was published by Yale School of Medicine.

Tuesday, March 8, 2022

OncLive presents: "Latest Perspective in Ovarian Cancer Care"

 

OncLive presents "Latest Perspective in Ovarian Cancer Care". Below are the topics that will be covered. Here is the link to watch this on-demand video.

Agenda Topics

 

The closer we look, the further we’ll go
Highlighting the current state of ovarian cancer and current treatments to understand the challenges faced by those living with ovarian cancer. 

What if the treatments were as unique as the tumor?
Understanding the history of where we’ve been with ovarian cancer, and what’s in store for the future, and your role in it.

To test is to know what to target
Exploring the advances in genomic profiling of ovarian cancer tumors and optimizing treatment outcomes for patients.

Using the journey to define the destination
Applying personalized treatments in practice and the impacts these can have on those living with ovarian cancer.

Monday, March 7, 2022

Ovarian Cancer Chemotherapy Resistance Linked to Gene Expression

 This article is from the Clearity Foundation website. 



A team led by researchers at the University of Helsinki has uncovered stress-related tumor and microenvironment gene expression features that appear to coincide with chemotherapy resistance and shorter progression-free survival in individuals with high-grade serous ovarian cancer.

The results, published in Science Advances on Wednesday, suggest that it may eventually be possible to better detect and manage those at risk of progression after chemotherapy treatment.

“Our findings help to identify already, prior to treatment, the tumors that are the most likely to have a poor response to therapy,” co-senior and co-corresponding author Anna Vähärautio, a researcher at the University of Helsinki, said in a statement. “Our results also suggest that therapies could be targeted at the inflammatory microenvironment of cancer cells and the surrounding tissue to improve treatment outcomes with the help of combination therapy.”

Vähärautio and her colleagues searched for transcriptome features corresponding with resistance to neoadjuvant chemotherapy using single-cell RNA sequence profiles for nearly 51,800 tumor, stromal, or immune cells from high-grade serous ovarian cancer samples collected prospectively from 11 patients at Turku University Hospital. They also considered RNA in situ hybridization data for 10 of the matched pre- and post-treatment tumor sets, along with bulk RNA-seq data for dozens more paired pre- and post-treatment or pre-treatment and relapse samples.

The team analyzed RNA-seq profiles in pre-treatment diagnostic laparoscopy samples and in post-chemotherapy samples obtained after debulking surgery using a computational method called PRIMUS that was designed to dial down patient-specific features to find shared transcriptional signals linked to chemotherapy response.

In ovarian cancer patients with chemotherapy-resistant tumors primed to progress to metastasis, they found a rise in stress-associated cell features that had been present in baseline samples.

“The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival,” the authors reported. “Co-occurrence with an inflammatory cancer-associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop.”

Those results lined up with patterns found in another 271 individuals with ovarian cancer who had their pre-treatment tumors tested by bulk RNA-seq through the Cancer Genome Atlas project, the researchers reported. Along with available gene expression profiles, they used reverse-phase protein array testing to distinguish between cases with stress-high or stress-low tumors.

That group included 86 individuals with high-grade serous ovarian tumors classified as stress-high and 144 individuals with stress-low tumors, the team noted. While the median progression-free survival time was 21.2 months for patients with stress-low tumors, it dropped to just shy of 15 months in the subset of patients with ovarian tumors showing high levels of stress-associated features.

With expression profiles for more than a dozen immune or stromal cell types that turned up in the tumor microenvironment samples, meanwhile, the researchers found related inflammation and paracrine signaling in stromal cells in the microenvironment of tumors showing stress-associated features, along with enhanced representation of cancer-associated fibroblast cells.

Based on these and other findings, the authors suggested that “a combination of induced and selective processes” contribute to the transcriptomic changes detected following chemotherapy — shifts that may be influenced by everything from tumor microenvironment features to differences in an individual’s underlying genetics and biology.

“[T]he identification of [a] stress signature opens avenues for combinatorial drug testing in preclinical models that maintain both subclonal heterogeneity and paracrine tumor-stromal signaling,” they concluded. “As many drugs targeting inflammatory effectors are already in clinical use for other indications, they may offer a realistic option for safe combinatorial therapies with a wide array of currently used oncological drugs to restrain the broadly adaptive stress response of tumors.”

This article was published by Genome Web.

Tuesday, March 1, 2022

Clearity Foundation: Help in Finding Clinical Trials

 

The Clearity Foundation has put together a search option to help you and your doctor select the best clinical trial for you. A link to that is below. If you haven't spent any time on the Clearity Foundation website, I would urge you to do so. It provides free counseling to women with OC and articles about research and links to treatment decision supports and what to do if you're newly diagnosed. 

In regards to finding clinical trials, there is a seven minute video tutorial that they have published on finding clinical trials You can find a link to this video here.

As per Clearity Foundation, "To find clinical trials, please check out the ovarian cancer-specific Trial Finder that Clearity has developed. The search outputs trials for which the patient is most likely to be eligible based on answers to questions about their specific clinical situation (e.g., prior treatments, tumor histology, platinum status), tumor biology, and preferences."

Thursday, February 24, 2022

Racial Disparities Persist in Ovarian Cancer

This article appeared on the Clearity Foundation web site and was written by Jon Kelvey

Black patients with ovarian cancer were less likely than their White counterparts to receive adjuvant chemotherapy after primary surgery, according to a study published in Gynecologic Oncology.

The study also showed that patients who did not undergo adjuvant chemotherapy had worse survival outcomes.

For this study, researchers analyzed National Cancer Database data on patients with stage II-III ovarian cancer who underwent primary surgery.
Of the 48,245 patients, 42,914 were White, 3058 were Black, and 2273 were another race. The patients’ median age was 61 years. There were 522 patients (1.08%) who did not receive adjuvant chemotherapy due to clinician-identified risk factors
.

In a multivariate analysis, the following factors were associated with not receiving a recommendation for adjuvant chemotherapy — Black race, being older (≥70 years), having higher Charlson-Deyo comorbidity scores (>0), having government insurance (vs private insurance), and being treated at a community center (vs academic/research center).

When controlling for all other factors, Black race was significantly associated with not being recommended chemotherapy (adjusted odds ratio, 2.12; 95% CI, 1.61-2.78; P <.0001).
Not being recommended for chemotherapy was associated with worse overall survival (OS). The median OS was 53.8 months for those who received adjuvant chemotherapy and 12.1 months for those who did not (adjusted hazard ratio [aHR], 2.74; 95% CI, 2.48-3.03; P <.0001).

OS outcomes were similar for Black and White patients who were not recommended for chemotherapy (aHR, 1.01; 95% CI, 0.74-1.39, P =.951).

Among Black patients, the 5-year OS rate was significantly higher for those who received a recommendation for chemotherapy than for those who did not — 40.3% and 25.9%, respectively (P <.0001).

The researchers noted that, of the 62 Black patients who were deemed too high risk to receive chemotherapy, 31 patients had a risk profile similar to the profiles of White patients who did receive chemotherapy.

These results suggest that risk estimation may be performed unequally on the basis of race. However, due to limitations of the data studied, the researchers could not rule out that other factors might help explain the observed disparity. One limitation is that functional status is not included in National Cancer Database records.

“Additional research is warranted to directly investigate the role of bias, including implicit bias, in clinical decision-making in gynecologic oncology,” the researchers concluded.

Reference
Matthews BJ, Qureshi MM, Fiascone SJ, et al. Racial disparities in non-recommendation of adjuvant chemotherapy in stage II-III ovarian cancerGynecol Oncol. 2022;164(1):27-33. doi:10.1016/j.ygyno.2021.10.090

This article was published by Cancer Therapy Advisor.