Gynecologic Oncology

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Gynecologic Oncology

United States
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WALTHAM, Mass., May 22, 2017 (GLOBE NEWSWIRE) -- TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, today announced the results of the Our Way Forward survey – a national survey of patients and healthcare providers developed to better understand the unmet education and support needs of the advanced ovarian cancer community. Created with input from leading ovarian cancer advocacy groups – National Ovarian Cancer Coalition (NOCC) and Ovarian Cancer Research Fund Alliance (OCRFA) – the results from the survey indicate that regardless of the stage of ovarian cancer, there is uncertainty among patients about what to expect after diagnosis – whether they are initially diagnosed or actively seeking greater resources and connections to lessen the burden of the disease. The Our Way Forward survey was conducted online in the U.S. by Harris Poll on behalf of TESARO, Inc. between April 2017 and May 2017 among 254 women living with ovarian cancer and 232 physicians who treat ovarian cancer patients. “Facing ovarian cancer can be extremely stressful and anxiety-provoking,” said Stephanie V. Blank, MD, Professor in the Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, and Director of Women's Health, Mount Sinai Downtown-Chelsea Center. “We can support survivors by better understanding their needs and perspectives, and how these evolve with time.” The survey reveals that around half (53 percent) of patients felt that ovarian cancer had a severe or very severe impact on their lives. For patients who are currently in treatment or who have been treated, about half (49 percent) admitted that they find not being sure of the path forward after diagnosis to be very or extremely challenging. According to the survey, more than two in five patients who are currently in treatment, or who have been treated, find not knowing what to expect during treatment (46 percent) or after treatment (47 percent) to be very or extremely challenging. These findings were significantly pronounced in women surveyed who experienced a recurrence of their disease. Women who experienced recurrence were more likely than those who have not experienced a recurrence to say they currently feel fear (32 percent vs. 15 percent), anxiety (36 percent vs. 22 percent) and uncertainty (31 percent vs. 18 percent). The overwhelming majority (87 percent) of women who have experienced recurrence report the thought of cancer returning can be overwhelming and more than half (58 percent) report the period of remission when they are no longer receiving therapy is sometimes worse than going through treatment. Understanding the gaps in perception among patients and healthcare providers, as well as anxiety and uncertainty that exists between the two, may help improve care and patient well-being throughout the ovarian cancer experience. More than seven in ten (71 percent) ovarian cancer patients reported getting very anxious before visits to their healthcare provider. More than a third (34 percent) of healthcare providers are unsure if, or do not feel that, they give their ovarian cancer patients all of the information they need about ovarian cancer. There are also differences in how often patients and healthcare providers perceive they are having discussions about treatment and expectations for managing ovarian cancer. Patients are craving information from their healthcare providers about expectations, treatment, recurrence and support. For example, 61 percent of patients said it would be very or extremely helpful to discuss with their healthcare provider how to cope with the unknown. “We are incredibly grateful for the community’s robust response to the survey,” said Mary Lynne Hedley, Ph.D., President and COO of TESARO. “As an organization, TESARO is committed to being a trusted partner to the ovarian cancer community and we hope to continue to work with NOCC and OCRFA to find a way forward on behalf of this underserved community and strengthen the emotional and education support that patients and oncologists have as it relates to ovarian cancer, no matter the stage of their disease.” Resources for Ovarian Cancer Patients The survey was conducted as part of TESARO’s Our Way Forward initiative (www.ourwayforward-oc.com), a call-to-action that encourages patients, their loved ones and physicians to rethink how they talk about advanced ovarian cancer and ways to partner together to navigate the physical and emotional challenges that the disease brings. As part of Our Way Forward, TESARO is committed to offering a series of resources for patients living with ovarian cancer, directly informed by the survey insights, including a discussion guide available for download that provides suggested questions and topics for the stages of ovarian cancer experience, including disease recurrence. TESARO is also partnering with “The Moth” for a special storytelling event, “Stories that Illuminate the Ovarian Cancer Experience,” which will provide a forum for patients, advocates and physicians to share their stories and for everyone in attendance to learn more about how to strengthen conversations to facilitate patient care and well-being. The first Our Way Forward storytelling event will be hosted in Chicago in June. About the Our Way Forward Survey          The Our Way Forward survey was conducted online in the U.S. by Harris Poll on behalf of TESARO, Inc. between April 13 and May 2, 2017, among 254 women 18+ years of age living in the U.S. who have been diagnosed with ovarian cancer. Survey respondents were selected from individuals who had agreed to participate in surveys through the Harris Poll and their partners or were recruited to participate by patient advocacy organizations, NOCC and OCRFA. Results are representative of only those surveyed. A parallel survey was conducted between April 17 and May 5, 2017, among 232 physicians who treat ovarian cancer patients in the U.S. consisting of 201 medical oncologists and 31 gynecologic oncologists. Survey respondents were selected from physicians who had agreed to participate in surveys through the Harris Poll and their partners. More information about the campaign, full survey methods and survey findings, including important resources to enhance conversations about ovarian cancer, are available on the Our Way Forward website at www.ourwayforward-oc.com and via NOCC at ovarian.org and OCRFA at ocrfa.org. About Ovarian Cancer  Approximately 22,000 women are diagnosed with ovarian cancer each year in the United States, and more than 65,000 women are diagnosed annually in Europe. Ovarian cancer is the fifth leading cause of cancer death among women. Despite high-response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85 percent of patients will experience recurrence within two years. Per NCCN guidelines, BRCA testing and genetic counseling remain important components of the medical workup for all patients upon a diagnosis with ovarian cancer. About National Ovarian Cancer Coalition (NOCC) Founded in 1991, the mission of the NOCC is to save lives by fighting tirelessly to prevent and cure ovarian cancer, and to improve the quality of life for Survivors. Through national programs and local NOCC chapter initiatives, the NOCC's goal is to educate communities and increase awareness about the symptoms of ovarian cancer. The NOCC also offers information to assist newly-diagnosed patients, hope to Survivors, and support to caregivers. The NOCC is also committed to the advancement of ovarian cancer research, specifically in funding the Ovarian Cancer Dream Team with Stand Up To Cancer®. About Ovarian Cancer Research Foundation Alliance (OCRFA) Ovarian Cancer Research Fund Alliance (OCRFA) is the largest global organization dedicated to fighting ovarian cancer.  OCRFA advances research to prevent, treat and defeat ovarian cancer, supports women and their families before, during and beyond diagnosis, and works with all levels of government to ensure ovarian cancer is a priority.  As the largest non-government funder of ovarian cancer research, OCRFA invests in innovative, promising research.  And OCRFA is the voice for the ovarian cancer community: fighting for more resources and policies on Capitol Hill, helping future health professionals recognize the disease through our Survivors Teaching Students® program, providing hope and insight by pairing newly diagnosed patients with our Woman to Woman program and connecting survivors at our Ovarian Cancer National Conference.  We are united to defeat ovarian cancer.  www.ocrfa.org About TESARO  TESARO is an oncology-focused biopharmaceutical company devoted to providing transformative therapies to people bravely facing cancer. For more information, visit www.tesarobio.com, and follow us on Twitter and LinkedIn.


News Article | April 26, 2017
Site: www.sciencedaily.com

Patients who expressed the tumor antigen NY-ESO-1 had more aggressive cancers and were more likely to die early from their disease, according to a large study conducted by Roswell Park Cancer Institute researchers and published online ahead of print in the journal Gynecologic Oncology. "This is the largest study of NY-ESO-1 expression in ovarian cancer patients, and the first time that expression of this antigen has been identified as a marker for more aggressive disease," says the study's first author, J. Brian Szender, MD, MPH, Fellow in the Department of Gynecologic Oncology at Roswell Park. NY-ESO-1 is one of the few tumor antigens that have restricted expression in normal tissue but become aberrantly expressed in epithelial ovarian cancers and other solid tumors. From January 2002 to June 2016, more than 1,000 patients with ovarian cancer were tested at Roswell Park for NY-ESO-1 expression. Their median age at diagnosis was 61 years, and most patients were diagnosed with stage IIIC or stage IV disease. The research team found that NY-ESO-1 expression was associated with shorter duration of both progression-free survival (22 months versus 25 months) and overall survival (42 months versus 50 months). During the study period, the Roswell Park scientists enrolled a total of 68 ovarian cancer patients with NY-ESO-1-positive tumors to cancer vaccine trials targeting NY-ESO-1. The researchers found that patients with NY-ESO-1-expressing tumors who were enrolled in cancer vaccine trials had significantly improved overall survival compared to patients with NY-ESO-1 who did not participate in the cancer vaccine trials, and with patients without NY-ESO-1-expressing tumors. "We suggest that NY-ESO-1 be a high-priority target for future immunotherapy studies, given the high prevalence of NY-ESO-1 expression in ovarian cancer and the association of this tumor antigen with adverse clinical outcomes," says Kunle Odunsi, MD, PhD, FRCOG, Deputy Director of Roswell Park and Chair of the Department of Gynecologic Oncology. "It is possible that in the coming years, NY-ESO-1 expression in ovarian cancer will be as important to the treating oncologist as HER2 expression is for the treatment of breast cancer."


News Article | May 15, 2017
Site: www.businesswire.com

PRINCETON, N.J.--(BUSINESS WIRE)--UPDATED — Advaxis, Inc. (NASDAQ:ADXS), a biotechnology company developing cancer immunotherapies, today published online a poster previously presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool that showed axalimogene filolisbac achieved durable response in a patient with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC). Sharad Ghamande, MD, principal investigator and Professor and Director of Gynecologic Oncology at the Georgia Cancer Center at Augusta University, discussed cervical cancer and axalimogene filolisbac in detail recently on the JENNIE Show on the News Channel ABC 6, WJBF in Augusta, GA. Also, one patient in this phase 1 study experienced an ongoing and durable partial response, and this patient was recently featured in the Augusta Chronicle, as she is being treated by Dr. Ghamande at the Georgia Cancer Center at Augusta University. Read the full Augusta Chronicle article here. Overall, nine patients who had documented disease progression after they had received curative treatments of chemotherapy and/or radiation with or without bevacizumab were enrolled in this phase 1, open-label, dose-determining study. Axalimogene filolisbac was well-tolerated across two dose levels. The study also established a recommended phase 2 dose of 1×1010 CFU and demonstrated antitumor activity at that dose. Axalimogene filolisbac was safely administered at 5 and 10 times the dose levels previously studied, without significant toxicity. “ The best overall tumor response in eight of the nine enrolled patients is encouraging in evaluating the potential of axalimogene filolisbac,” said Dr. Ghamande. “ We were pleased to see a sustained and durable partial response in one patient, which is very rare for this kind of tumor that is unresponsive to chemotherapy, and survival in these patients is often less than 10 months. In addition, we could safely administer the drug at 5 and 10 times the dose levels previously studied, without any significant toxicity.” There was only one instance of dose-limiting toxicity, with that patient experiencing a grade 3 treatment related adverse event (TRAE) of hypotension at a dose of 5×109 CFU. Across all doses, eight of nine patients experienced a grade 1-2 TRAE, including chills, nausea and hypotension. The poster on the phase 1 data, “ High-dose treatment with ADXS11-001, a Listeria monocytogenes-listeriolysin O (Lm-LLO) immunotherapy, in women with cervical cancer: a phase I, dose-escalation study” (no. 58) is available at www.advaxis.com. The company is preparing to initiate a phase 3 trial in PRmCC later this year. Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors. Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications. Located in Princeton, N.J., Advaxis, Inc. is a biotechnology company developing multiple cancer immunotherapies based on its proprietary Lm Technology™. The Lm Technology, using bioengineered live attenuated Listeria monocytogenes (Lm) bacteria, is the only known cancer immunotherapy agent shown in preclinical studies to both generate cancer fighting T cells directed against cancer antigens and neutralize Tregs and myeloid-derived suppressor cells (MDSCs) that protect the tumor microenvironment from immunologic attack and contribute to tumor growth. Advaxis' lead Lm Technology immunotherapy, axalimogene filolisbac, targets HPV-associated cancers and is in clinical trials for three potential indications: Phase 3 in invasive cervical cancer, Phase 2 in head and neck cancer, and Phase 2 in anal cancer. The FDA has granted axalimogene filolisbac orphan drug designation for each of these three clinical settings, as well as Fast Track designation for adjuvant therapy for HRLACC patients and a SPA for the Phase 3 AIM2CERV trial in HRLACC patients. Axalimogene filolisbac has also been classified as an advanced therapy medicinal product for the treatment of cervical cancer by the EMA’s CAT. Advaxis has two additional immunotherapy products: ADXS-PSA in prostate cancer and ADXS-HER2 in HER2 expressing solid tumors, in human clinical development. In addition, Advaxis and Amgen are developing ADXS-NEO, an investigational cancer immunotherapy treatment designed to activate a patient's immune system to respond against the unique mutations, or neoepitopes, contained in and identified from each individual patient's tumor, with plans to commence a Phase 1 clinical trial in 2017. To learn more about Advaxis, visit www.advaxis.com and connect on Twitter, LinkedIn, Facebook, and YouTube. This press release contains forward-looking statements, including, but not limited to, statements regarding Advaxis’ ability to develop the next generation of cancer immunotherapies, and the safety and efficacy of Advaxis’ proprietary immunotherapy, axalimogene filolisbac. These forward-looking statements are subject to a number of risks including the risk factors set forth from time to time in Advaxis’ SEC filings including, but not limited to, its report on Form 10-K for the fiscal year ended October 31, 2016, which is available at http://www.sec.gov. Any forward-looking statements set forth in this presentation speak only as of the date of this presentation. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof other than as required by law. You are cautioned not to place undue reliance on any forward-looking statements.


News Article | May 23, 2017
Site: www.eurekalert.org

CAMBRIDGE, MA -- Most women diagnosed with ovarian cancer undergo surgery to remove as many of the tumors as possible. However, it is usually impossible to eliminate all of the cancer cells because they have spread throughout the abdomen. Surgery is therefore followed by 18 weeks of chemotherapy. Delivering chemotherapy drugs directly to the abdomen through a catheter offers better results than other methods, but this regimen suffers from significant complications, and many patients are unable to complete it. MIT researchers who are working on an implantable device that could make intraperitoneal chemotherapy more bearable have published a new study that offers insight into how to improve chemotherapy strategies for ovarian cancer, and how to determine which patients would be most likely to benefit from this device. "As we entered into this project, our question was how do we get the same beneficial outcomes and reduce all the side effects?" says Michael Cima, the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering, a member of MIT's Koch Institute for Integrative Cancer Research, and the senior author of the study. The findings suggest that the outcome of initial surgery plays a key role in the effectiveness of subsequent intraperitoneal chemotherapy. Cisplatin, one of the most commonly used drugs, effectively treats very tiny tumor cell clusters when it is delivered continuously or as a single large dose. But the researchers found that for larger tumor cell clusters, continuous delivery of cisplatin, at higher doses than are tolerable with the current periodic chemotherapy method, was more effective. The device they are developing would make delivery of such higher, continuous doses possible. Laura Tanenbaum, a recent MIT PhD recipient, is the lead author of the paper, which appears in the journal Gynecologic Oncology. Other authors are MIT graduate students Aikaterini Mantzavinou and Kriti Subramanyam, and Massachusetts General Hospital gynecologic oncologist Marcela del Carmen. Ovarian cancer is usually not detected until the cancer has reached an advanced stage, with metastases covering organs throughout the peritoneal cavity, including the liver, bladder, and intestines. After surgery, known as "tumor debulking," patients receive two types of chemotherapy to treat tumors left behind: intravenous delivery of paclitaxel and intravenous or intraperitoneal delivery of a platinum drug such as cisplatin. Intraperitoneal chemotherapy is pumped directly into the abdomen through a catheter every three weeks for a total of six cycles. This allows cisplatin to come in direct contact with the residual tumors, which has been shown to be more effective than intravenous delivery but is not tolerable for many patients. "It's painful and the catheter can be a site of local infections," Cima says. Several years ago, Cima and colleagues set out to develop an implantable device that could deliver cisplatin into the abdomen without all of the side effects produced by the catheter and the large, repeated cisplatin doses. Their device is made of a drug-loaded polymer that could be inserted at the beginning of treatment and remain in place for the full treatment course, then removed with minimally invasive surgery. The researchers have tested proof-of-concept devices in mice and are now developing a version that could be tested in humans, though more animal studies are needed before human trials can begin. In their new study, the researchers set out to investigate how the size of the residual tumors would affect their response to continuous, low-dose cisplatin delivery. They believed that size would play some role because once tumors reach a certain size, the drug may not be able to penetrate all the way into the inner core of the tumors. To test this hypothesis, the researchers grew spherical ovarian cancer cell clusters 100 or 200 microns in diameter in a lab dish and exposed them to varying doses of cisplatin. Continuous, low-dose cisplatin delivery, similar to what tumors would receive from an implanted device, was as effective against 100-micron tumor spheroids as a single high dose, similar to that delivered by a catheter. However, by increasing the continuous cisplatin dose, the researchers found that they could treat the larger 200-micron spheroids more effectively than they could with the single high dose. This increased dose could be delivered using an implantable device, but it would not be tolerable for patients if given through an abdominal catheter. Cima believes that the findings may also help to explain some of the preliminary results of a recent, large clinical trial in which doctors found that intraperitoneal cisplatin delivery was no more effective than intravenous chemotherapy alone. This contradicted previous findings from smaller studies, indicating that cisplatin delivery by catheter improved patient survival. In the newer trial, conducted at about 500 treatment centers, surgeons admitted patients to the study based on size estimates of the tumors remaining after surgery. However, Cima says, this subjective evaluation may have resulted in patients entering the study whose tumors were too large to be helped by the current intraperitoneal therapy. This points to the importance of both developing a good method for screening patients before future trials begin, to make sure they are likely to benefit from the treatment, and devising new strategies to help surgeons remove as many tumors as possible, Cima says. The research was funded by the Koch Institute-Dana Farber/Harvard Cancer Center Bridge Project, the Koch Institute Frontier Research Program, the Kathy and Curt Marble Cancer Research Fund, the MIT Tata Center for Technology and Design, and the Koch Institute Support (core) Grant from the National Cancer Institute.


News Article | May 25, 2017
Site: www.sciencedaily.com

Most women diagnosed with ovarian cancer undergo surgery to remove as many of the tumors as possible. However, it is usually impossible to eliminate all of the cancer cells because they have spread throughout the abdomen. Surgery is therefore followed by 18 weeks of chemotherapy. Delivering chemotherapy drugs directly to the abdomen through a catheter offers better results than other methods, but this regimen suffers from significant complications, and many patients are unable to complete it. MIT researchers who are working on an implantable device that could make intraperitoneal chemotherapy more bearable have published a new study that offers insight into how to improve chemotherapy strategies for ovarian cancer, and how to determine which patients would be most likely to benefit from this device. "As we entered into this project, our question was how do we get the same beneficial outcomes and reduce all the side effects?" says Michael Cima, the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering, a member of MIT's Koch Institute for Integrative Cancer Research, and the senior author of the study. The findings suggest that the outcome of initial surgery plays a key role in the effectiveness of subsequent intraperitoneal chemotherapy. Cisplatin, one of the most commonly used drugs, effectively treats very tiny tumor cell clusters when it is delivered continuously or as a single large dose. But the researchers found that for larger tumor cell clusters, continuous delivery of cisplatin, at higher doses than are tolerable with the current periodic chemotherapy method, was more effective. The device they are developing would make delivery of such higher, continuous doses possible. Laura Tanenbaum, a recent MIT PhD recipient, is the lead author of the paper, which appears in the journal Gynecologic Oncology. Other authors are MIT graduate students Aikaterini Mantzavinou and Kriti Subramanyam, and Massachusetts General Hospital gynecologic oncologist Marcela del Carmen. Ovarian cancer is usually not detected until the cancer has reached an advanced stage, with metastases covering organs throughout the peritoneal cavity, including the liver, bladder, and intestines. After surgery, known as "tumor debulking," patients receive two types of chemotherapy to treat tumors left behind: intravenous delivery of paclitaxel and intravenous or intraperitoneal delivery of a platinum drug such as cisplatin. Intraperitoneal chemotherapy is pumped directly into the abdomen through a catheter every three weeks for a total of six cycles. This allows cisplatin to come in direct contact with the residual tumors, which has been shown to be more effective than intravenous delivery but is not tolerable for many patients. "It's painful and the catheter can be a site of local infections," Cima says. Several years ago, Cima and colleagues set out to develop an implantable device that could deliver cisplatin into the abdomen without all of the side effects produced by the catheter and the large, repeated cisplatin doses. Their device is made of a drug-loaded polymer that could be inserted at the beginning of treatment and remain in place for the full treatment course, then removed with minimally invasive surgery. The researchers have tested proof-of-concept devices in mice and are now developing a version that could be tested in humans, though more animal studies are needed before human trials can begin. In their new study, the researchers set out to investigate how the size of the residual tumors would affect their response to continuous, low-dose cisplatin delivery. They believed that size would play some role because once tumors reach a certain size, the drug may not be able to penetrate all the way into the inner core of the tumors. To test this hypothesis, the researchers grew spherical ovarian cancer cell clusters 100 or 200 microns in diameter in a lab dish and exposed them to varying doses of cisplatin. Continuous, low-dose cisplatin delivery, similar to what tumors would receive from an implanted device, was as effective against 100-micron tumor spheroids as a single high dose, similar to that delivered by a catheter. However, by increasing the continuous cisplatin dose, the researchers found that they could treat the larger 200-micron spheroids more effectively than they could with the single high dose. This increased dose could be delivered using an implantable device, but it would not be tolerable for patients if given through an abdominal catheter. Cima believes that the findings may also help to explain some of the preliminary results of a recent, large clinical trial in which doctors found that intraperitoneal cisplatin delivery was no more effective than intravenous chemotherapy alone. This contradicted previous findings from smaller studies, indicating that cisplatin delivery by catheter improved patient survival. In the newer trial, conducted at about 500 treatment centers, surgeons admitted patients to the study based on size estimates of the tumors remaining after surgery. However, Cima says, this subjective evaluation may have resulted in patients entering the study whose tumors were too large to be helped by the current intraperitoneal therapy. This points to the importance of both developing a good method for screening patients before future trials begin, to make sure they are likely to benefit from the treatment, and devising new strategies to help surgeons remove as many tumors as possible, Cima says.


News Article | May 26, 2017
Site: www.biosciencetechnology.com

Most women diagnosed with ovarian cancer undergo surgery to remove as many of the tumors as possible. However, it is usually impossible to eliminate all of the cancer cells because they have spread throughout the abdomen. Surgery is therefore followed by 18 weeks of chemotherapy. Delivering chemotherapy drugs directly to the abdomen through a catheter offers better results than other methods, but this regimen suffers from significant complications, and many patients are unable to complete it. MIT researchers who are working on an implantable device that could make intraperitoneal chemotherapy more bearable have published a new study that offers insight into how to improve chemotherapy strategies for ovarian cancer, and how to determine which patients would be most likely to benefit from this device. “As we entered into this project, our question was how do we get the same beneficial outcomes and reduce all the side effects?” said Michael Cima, the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study. The findings suggest that the outcome of initial surgery plays a key role in the effectiveness of subsequent intraperitoneal chemotherapy. Cisplatin, one of the most commonly used drugs, effectively treats very tiny tumor cell clusters when it is delivered continuously or as a single large dose. But the researchers found that for larger tumor cell clusters, continuous delivery of cisplatin, at higher doses than are tolerable with the current periodic chemotherapy method, was more effective. The device they are developing would make delivery of such higher, continuous doses possible. Laura Tanenbaum, who recently received her Ph.D. from the Harvard-MIT Program in Health Sciences and Technology (HST), and HST PhD student Aikaterini Mantzavinou are the lead authors of the paper, which appears in the journal Gynecologic Oncology. Other authors are HST Ph.D. student Kriti Subramanyam and Massachusetts General Hospital gynecologic oncologist Marcela del Carmen. Ovarian cancer is usually not detected until the cancer has reached an advanced stage, with metastases covering organs throughout the peritoneal cavity, including the liver, bladder, and intestines. After surgery, known as “tumor debulking,” patients receive two types of chemotherapy to treat tumors left behind: intravenous delivery of paclitaxel and intravenous or intraperitoneal delivery of a platinum drug such as cisplatin. Intraperitoneal chemotherapy is pumped directly into the abdomen through a catheter every three weeks for a total of six cycles. This allows cisplatin to come in direct contact with the residual tumors, which has been shown to be more effective than intravenous delivery but is not tolerable for many patients. “It’s painful and the catheter can be a site of local infections,” Cima said. Several years ago, Cima and colleagues set out to develop an implantable device that could deliver cisplatin into the abdomen without all of the side effects produced by the catheter and the large, repeated cisplatin doses. As this project was neither traditional clinical research nor fundamental scientific research, enabling support came from the Koch Institute’s Frontier Research Program and then later on, the Bridge Project, a partnership between MIT’s Koch Institute and the Dana-Farber/Harvard Cancer Center. Their device is made of a drug-loaded polymer that could be inserted at the beginning of treatment and remain in place for the full treatment course, then removed with minimally invasive surgery. The researchers have tested proof-of-concept devices in mice and are now developing a version that could be tested in humans, though more animal studies are needed before human trials can begin. In their new study, the researchers set out to investigate how the size of the residual tumors would affect their response to continuous, low-dose cisplatin delivery. They believed that size would play some role because once tumors reach a certain size, the drug may not be able to penetrate all the way into the inner core of the tumors. To test this hypothesis, the researchers grew spherical ovarian cancer cell clusters 100 or 200 microns in diameter in a lab dish and exposed them to varying doses of cisplatin. Continuous, low-dose cisplatin delivery, similar to what tumors would receive from an implanted device, was as effective against 100-micron tumor spheroids as a single high dose, similar to that delivered by a catheter. However, by increasing the continuous cisplatin dose, the researchers found that they could treat the larger 200-micron spheroids more effectively than they could with the single high dose. This increased dose could be delivered using an implantable device, but it would not be tolerable for patients if given through an abdominal catheter. Cima believes that the findings may also help to explain some of the preliminary results of a recent, large clinical trial in which doctors found that intraperitoneal cisplatin delivery was no more effective than intravenous chemotherapy alone. This contradicted previous findings from smaller studies, indicating that cisplatin delivery by catheter improved patient survival. In the newer trial, conducted at about 500 treatment centers, surgeons admitted patients to the study based on size estimates of the tumors remaining after surgery. However, Cima said, this subjective evaluation may have resulted in patients entering the study whose tumors were too large to be helped by the current intraperitoneal therapy. This points to the importance of both developing a good method for screening patients before future trials begin, to make sure they are likely to benefit from the treatment, and devising new strategies to help surgeons remove as many tumors as possible, Cima said.


News Article | May 26, 2017
Site: www.biosciencetechnology.com

Most women diagnosed with ovarian cancer undergo surgery to remove as many of the tumors as possible. However, it is usually impossible to eliminate all of the cancer cells because they have spread throughout the abdomen. Surgery is therefore followed by 18 weeks of chemotherapy. Delivering chemotherapy drugs directly to the abdomen through a catheter offers better results than other methods, but this regimen suffers from significant complications, and many patients are unable to complete it. MIT researchers who are working on an implantable device that could make intraperitoneal chemotherapy more bearable have published a new study that offers insight into how to improve chemotherapy strategies for ovarian cancer, and how to determine which patients would be most likely to benefit from this device. “As we entered into this project, our question was how do we get the same beneficial outcomes and reduce all the side effects?” said Michael Cima, the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study. The findings suggest that the outcome of initial surgery plays a key role in the effectiveness of subsequent intraperitoneal chemotherapy. Cisplatin, one of the most commonly used drugs, effectively treats very tiny tumor cell clusters when it is delivered continuously or as a single large dose. But the researchers found that for larger tumor cell clusters, continuous delivery of cisplatin, at higher doses than are tolerable with the current periodic chemotherapy method, was more effective. The device they are developing would make delivery of such higher, continuous doses possible. Laura Tanenbaum, who recently received her Ph.D. from the Harvard-MIT Program in Health Sciences and Technology (HST), and HST PhD student Aikaterini Mantzavinou are the lead authors of the paper, which appears in the journal Gynecologic Oncology. Other authors are HST Ph.D. student Kriti Subramanyam and Massachusetts General Hospital gynecologic oncologist Marcela del Carmen. Ovarian cancer is usually not detected until the cancer has reached an advanced stage, with metastases covering organs throughout the peritoneal cavity, including the liver, bladder, and intestines. After surgery, known as “tumor debulking,” patients receive two types of chemotherapy to treat tumors left behind: intravenous delivery of paclitaxel and intravenous or intraperitoneal delivery of a platinum drug such as cisplatin. Intraperitoneal chemotherapy is pumped directly into the abdomen through a catheter every three weeks for a total of six cycles. This allows cisplatin to come in direct contact with the residual tumors, which has been shown to be more effective than intravenous delivery but is not tolerable for many patients. “It’s painful and the catheter can be a site of local infections,” Cima said. Several years ago, Cima and colleagues set out to develop an implantable device that could deliver cisplatin into the abdomen without all of the side effects produced by the catheter and the large, repeated cisplatin doses. As this project was neither traditional clinical research nor fundamental scientific research, enabling support came from the Koch Institute’s Frontier Research Program and then later on, the Bridge Project, a partnership between MIT’s Koch Institute and the Dana-Farber/Harvard Cancer Center. Their device is made of a drug-loaded polymer that could be inserted at the beginning of treatment and remain in place for the full treatment course, then removed with minimally invasive surgery. The researchers have tested proof-of-concept devices in mice and are now developing a version that could be tested in humans, though more animal studies are needed before human trials can begin. In their new study, the researchers set out to investigate how the size of the residual tumors would affect their response to continuous, low-dose cisplatin delivery. They believed that size would play some role because once tumors reach a certain size, the drug may not be able to penetrate all the way into the inner core of the tumors. To test this hypothesis, the researchers grew spherical ovarian cancer cell clusters 100 or 200 microns in diameter in a lab dish and exposed them to varying doses of cisplatin. Continuous, low-dose cisplatin delivery, similar to what tumors would receive from an implanted device, was as effective against 100-micron tumor spheroids as a single high dose, similar to that delivered by a catheter. However, by increasing the continuous cisplatin dose, the researchers found that they could treat the larger 200-micron spheroids more effectively than they could with the single high dose. This increased dose could be delivered using an implantable device, but it would not be tolerable for patients if given through an abdominal catheter. Cima believes that the findings may also help to explain some of the preliminary results of a recent, large clinical trial in which doctors found that intraperitoneal cisplatin delivery was no more effective than intravenous chemotherapy alone. This contradicted previous findings from smaller studies, indicating that cisplatin delivery by catheter improved patient survival. In the newer trial, conducted at about 500 treatment centers, surgeons admitted patients to the study based on size estimates of the tumors remaining after surgery. However, Cima said, this subjective evaluation may have resulted in patients entering the study whose tumors were too large to be helped by the current intraperitoneal therapy. This points to the importance of both developing a good method for screening patients before future trials begin, to make sure they are likely to benefit from the treatment, and devising new strategies to help surgeons remove as many tumors as possible, Cima said.


News Article | February 15, 2017
Site: www.prweb.com

Pierian Biosciences, the premier developer of life science technologies providing treatment directing data to aid physicians in selecting the most appropriate therapy for their patients with cancer, has named Mark S. Gelder, MD, as chief medical officer. “We rely on Mark to ensure the delivery of quality diagnostic assays: the immune-proximity assay, CEER®, recently renamed PathwayINTELTM, and our drug response profiling assay, MiCK®, recently renamed ChemoINTELTM,” says Robert Henry, president and chief executive officer of Pierian Biosciences. “We’ll also be looking for Mark to help us maintain our industry presence and guide the development of collaborative agreements with partners such as academic centers, pharmaceutical companies and oncologists.” In addition, Gelder provides medical, clinical and scientific oversight as well as helping to define the company’s strategic direction. Dr. Gelder brings more than 25 years of oncology clinical trial and drug development experience to Pieiran. He is board certified in Internal Medicine, Obstetrics and Gynecology and Gynecologic Oncology. As an experienced researcher and clinician, he has significant regulatory experience working closely with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and in various leadership roles at pharmaceutical companies including Pfizer, Wyeth, Bayer, GE Healthcare, Heron Therapeutics and Inovio Pharmaceuticals. A graduate of the University of Virginia School of Medicine, Gelder received his residency training in internal medicine at University of Virginia and an additional residency in obstetrics and gynecology at the University of Alabama at Birmingham. While at UAB, Gelder also completed a fellowship in gynecologic oncology. He is currently a fellow of the American College of Obstetrics and Gynecology. Pierian’s PathwayINTEL is a functional proteomic profiling assay which provides quantitative information on the expression and activation status of proteins of interest to identify the true oncogenic “driver” and allow selection of the most appropriate targeted and/or biologic therapy for cancer patients. ChemoINTEL, the company’s functional drug response profiling assay, provides actionable information to guide selection on the effectiveness of cytotoxic agents to enhance clinical treatment decision-making. About Pierian Biosciences Based in Franklin, Tenn., Pierian Biosciences is a privately held life sciences and clinical pathology laboratory company offering treatment-directing diagnostic data to support more effective and lower cost cancer treatment. The company’s technology includes the ChemoINTEL and the PathwayINTEL Assay platforms. The company has laboratories in Franklin, Tenn. and San Diego, CA. For more information visit http://pierianbio.com.


News Article | February 15, 2017
Site: www.eurekalert.org

A team of 18 University of California San Diego School of Medicine and Moores Cancer Center researchers has developed a new tool to analyze an often overlooked aspect of cancer genetics -- an alteration that results in the loss or gain in a copy of a gene. This change, known as somatic copy-number alterations, may be key to disease progression and might offer new therapeutic approaches for ovarian cancer and other malignancies. "When most people think about cancer genetics, they think about single key mutations that foster tumor formation -- very specific things like the BRCA genes," said Joe R. Delaney, PhD, a fellow in the Clinical Translation program at UC San Diego Moores Cancer Center and lead author of the paper published February 15 in Nature Communications. "These changes are often referred to as tumor drivers but these are not the only deviations that impact cancer growth. We explored other possibilities." More than 90 percent of genetic changes in cancer cells involve the loss or gain of a single copy of a gene, rather than a mutation. A tumor cell might have one copy or three instead of the normal two copies -- one provided by each parent. This area has not been explored in depth, since experience with other diseases has taught scientists that the loss of one gene copy might not lead to disease symptoms because the second copy provided by the other parent fills in. Delaney and team wondered if this were true if several single gene copies that cooperated for the same cellular function were lost, and what the patterns might be in different cancers. The team designed the Haploinsufficient/Triplosensitive Gene (HAPTRIG) computational tool to identify pathways significantly disrupted by the loss and gain of genes. Ovarian cancer in particular is fraught with these alterations -- with more than 60 percent of genes affected. When the team analyzed this malignancy using HAPTRIG, the pathway that stood out was autophagy -- a natural process of cell death that helps maintain normal cellular health. Ovarian cancer cells use autophagy all of the time, but also lose several copies of autophagy genes resulting in a compromised capacity. The researchers then used a combination of existing United States Food and Drug Administration-approved drugs to target autophagy and found ovarian cancer cells to be highly sensitive to these drugs in several different mouse cancer models -- even among cells resistant to standard chemotherapy. The combination of drugs appeared less toxic than standard chemotherapy, were relatively inexpensive and should be clinically evaluated, said Dwayne G. Stupack, PhD, the study's senior author and associate professor in the dDivision of Gynecologic Oncology at Moores Cancer Center. With further work, said the authors, this finding could lead to new approaches to treat chemotherapy-resistant disease, and could enhance treatment of other cancers as well. "Our study suggests that a roadmap of targetable genetic changes in tumors should not be limited to mutations," said Stupack. "HAPTRIG may reveal additional targetable pathways across cancer types. We have provided a free web-tool to allow the community to easily perform a HAPTRIG analysis on 21 cancer types."


News Article | February 15, 2017
Site: www.rdmag.com

A team of 18 University of California San Diego School of Medicine and Moores Cancer Center researchers has developed a new tool to analyze an often overlooked aspect of cancer genetics -- an alteration that results in the loss or gain in a copy of a gene. This change, known as somatic copy-number alterations, may be key to disease progression and might offer new therapeutic approaches for ovarian cancer and other malignancies. "When most people think about cancer genetics, they think about single key mutations that foster tumor formation -- very specific things like the BRCA genes," said Joe R. Delaney, PhD, a fellow in the Clinical Translation program at UC San Diego Moores Cancer Center and lead author of the paper published February 15 in Nature Communications. "These changes are often referred to as tumor drivers but these are not the only deviations that impact cancer growth. We explored other possibilities." More than 90 percent of genetic changes in cancer cells involve the loss or gain of a single copy of a gene, rather than a mutation. A tumor cell might have one copy or three instead of the normal two copies -- one provided by each parent. This area has not been explored in depth, since experience with other diseases has taught scientists that the loss of one gene copy might not lead to disease symptoms because the second copy provided by the other parent fills in. Delaney and team wondered if this were true if several single gene copies that cooperated for the same cellular function were lost, and what the patterns might be in different cancers. The team designed the Haploinsufficient/Triplosensitive Gene (HAPTRIG) computational tool to identify pathways significantly disrupted by the loss and gain of genes. Ovarian cancer in particular is fraught with these alterations -- with more than 60 percent of genes affected. When the team analyzed this malignancy using HAPTRIG, the pathway that stood out was autophagy -- a natural process of cell death that helps maintain normal cellular health. Ovarian cancer cells use autophagy all of the time, but also lose several copies of autophagy genes resulting in a compromised capacity. The researchers then used a combination of existing United States Food and Drug Administration-approved drugs to target autophagy and found ovarian cancer cells to be highly sensitive to these drugs in several different mouse cancer models -- even among cells resistant to standard chemotherapy. The combination of drugs appeared less toxic than standard chemotherapy, were relatively inexpensive and should be clinically evaluated, said Dwayne G. Stupack, PhD, the study's senior author and associate professor in the dDivision of Gynecologic Oncology at Moores Cancer Center. With further work, said the authors, this finding could lead to new approaches to treat chemotherapy-resistant disease, and could enhance treatment of other cancers as well. "Our study suggests that a roadmap of targetable genetic changes in tumors should not be limited to mutations," said Stupack. "HAPTRIG may reveal additional targetable pathways across cancer types. We have provided a free web-tool to allow the community to easily perform a HAPTRIG analysis on 21 cancer types."

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