GPs Should Suspect Ovarian Cancer in All Women With Distended Abdomen, U.K. Researchers Warn

“GPs [General Practioners] should suspect ovarian cancer in all women presenting with abdominal distension, [U.K.] researchers have warned.  The primary care study found it was an important enough symptom on its own to warrant further investigation.  Researchers linked seven symptoms to ovarian cancer with many commonly present as much as six months before diagnosis, and warned that their study dispelled the myth that ovarian cancer was a ‘silent killer’. …”

“GPs [General Practioners] should suspect ovarian cancer in all women presenting with abdominal distension, researchers have warned.

The primary care study found it was an important enough symptom on its own to warrant further investigation.

Researchers linked seven symptoms to ovarian cancer with many commonly present as much as six months before diagnosis, and warned that their study dispelled the myth that ovarian cancer was a ‘silent killer’.

As many as 2.5% of women with abdominal distension on its own were subsequently diagnosed with ovarian cancer, and an ovarian cancer diagnosis was 240 times more likely in these women than in controls.

Urinary frequency and abdominal pain were also associated with risk, with the relative risk of ovarian cancer increasing by 16- and 12-fold respectively, although the positive predictive values of the symptoms on their own were only 0.2% and 0.3%.

Abdominal distension, urinary frequency and abdominal pain remained independently associated with cancer more than six months prior to diagnosis.

Dr. Willie Hamilton, a GP and a senior research fellow in primary care at the University of Bristol, said his preliminary results provided an evidence base for GPs to select patients for further investigation: ‘Abdominal distension is important enough to warrant investigation for ovarian cancer even without the need for other symptoms.’  ‘Ovarian cancer is not a silent killer, it’s just its noise seems to go unheard by GPs at times’, he added.

The study, presented at the Society for Academic Primary Care south west annual research meeting last week, examined the records of 212 women diagnosed with ovarian cancer at 39 practices in Devon in the year before diagnosis, and compared them with 1,030 matched controls.

Dr. Murray Freeman, a GP in Birkenhead, Merseyside and cancer lead for Wirral PCT, said the study ‘highlights how often ovarian cancer masquerades as other common illnesses’. ‘GPs should have a low index of suspicion in women over 40 with non specific symptoms – and refer or investigate early.’

Dr. Nick Brown, a GP in Chippenham, Wiltshire with an interest in cancer, said GPs desperately needed a tool to aid earlier diagnosis. ‘Small tumours are very difficult to diagnosis, even by doing a pelvic or vaginal examination. By the time tumours reach the size they can be detected it may have spread and treatment might not be that easy.’

Positive predictive values of ovarian cancer symptoms –

• Abdominal distensions – 2.5%
• Post-menopausal bleeding
• Loss of appetite – 0.6%
• Urinary frequency – 0.2%
• Abdominal pain – 0.3%
• Rectal bleeding – 0.2%
• Abdominal bloating – 0.3%

Source: Society for Academic Primary Care, South West Annual Research Meeting, March 2009, oral presentation”

Quoted SourceSuspect Ovarian Cancer In All Women With Distended Abdomen, by Lilian Anekwe, Pulsetoday.co.uk, Mar. 9, 2009.

WGRZ News in Buffalo NY Reports Meghan’s Story: An 8th Grader Battles Ovarian Cancer

Meghan Redenbach is an 8th grader who is battling a rare form of ovarian cancer

Meghan Redenbach is an 8th grader who is battling a rare form of ovarian cancer. (Source: WGRZ News, Buffalo, NY)

On February 26, 2009, Libby’s H*O*P*E*™ posted a story about Meghan Redenbach.  As you may recall, Meghan Redenbach , 13 years old, was diagnosed in December 2008 with a rare form of ovarian cancer known as “fibrosarcoma.”  This form of ovarian cancer is so rare that there are only 30 documented cases in the U.S.  Meghan is only the second child to be diagnosed with fibrosarcoma.

Today, we were thrilled that WGRZ News, located in Buffalo, New York, also reported on Meghan’s story.  If you are interested in watching the 5 minute video news story created by WGRZ’s Matt Pearl, CLICK HERE.

Donations are being accepted to help with Meghan’s mounting medical expenses. Donations can either be mailed to: Meghan’s Fund c/o First Niagara Bank, 5737 South Transit Road, Lockport, New York 14094, or you can make an on-line donation by credit card or through your Pay-Pal account by clicking on the “Make A Donation” tab at www.meghansfund.org.

Primary SourceMeghan’s Story: An 8th Grader Battles Ovarian Cancer, by Matt Pearl, WGRZ News, March 5, 2009.

ProLindac Produces 66% Disease Stabilization In Heavily-Pretreated Patients Within Phase II Study High Dose Groups

“… ACCESS PHARMACEUTICALS, INC. … , announced today positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac(TM) in late-stage, heavily pretreated ovarian cancer patients. In this monotherapy study 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST [Response Evaluation Criteria in Solid Tumors] criteria. No patient in any dose group exhibited any signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin, and ProLindac was well tolerated overall. The maximum tolerated dose of ProLindac was established as well as the recommended dose levels for future combination studies. …”

66% of evaluable heavily-pretreated patients in the high dose groups achieved disease stabilization. ProLindac was well tolerated overall.

DALLAS, March 5 /PRNewswire-FirstCall/ — ACCESS PHARMACEUTICALS, INC. (OTCBB: ACCP), announced today positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac(TM) in late-stage, heavily pretreated ovarian cancer patients. In this monotherapy study 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST [Response Evaluation Criteria in Solid Tumors] criteria. No patient in any dose group exhibited any signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin, and ProLindac was well tolerated overall. The maximum tolerated dose of ProLindac was established as well as the recommended dose levels for future combination studies.

‘We are very pleased with these results. ProLindac was well tolerated in an absolute sense and relative to commercially-available platinum therapies. We saw significant DACH platinum activity and efficacy in patients at the highest dose levels which is very encouraging given that this study involved monotherapy in a heavily pretreated patient population that typically only respond to an aggressive drug combination,’ commented Dr. David Nowotnik, Access’ Senior Vice President R&D. ‘The DACH platinum activity level seen benchmarked favorably with published studies of monotherapy oxaliplatin in similar but less heavily pre-treated patient populations. Having achieved the recommended dose for future combination studies, we look forward to moving ahead in the clinic ourselves and with our regional partners.’

This 26 patient Phase 2 study explored 3 different dose levels and 2 dosing regimens of ProLindac as a monotherapy treatment for advanced ovarian cancer, to provide data on the monotherapy anticancer activity and safety of ProLindac. Of patients eligible for evaluation according to standard RECIST criteria, clinically-meaningful disease stabilization was achieved in 42% of all patients, and 66% of all patients in the higher dose groups. Sustained and significant reductions in Ca-125, the established specific serum marker for ovarian cancer, were also observed in several patients.

‘We are delighted that the results from this study support our belief that ProLindac is an active platinum agent with a favorable side effect profile,’ stated Jeffrey B. Davis, Access’ President & CEO. ‘These data provide us with a strong incentive to continue the clinical development of ProLindac. As previously announced, we are currently planning a number of combination trials, looking at combining ProLindac with other cancer agents, such as taxol and gemcitabine, in multiple solid tumor indications including colorectal and ovarian.’

Access has previously announced that it has licensed ProLindac to Jiangsu Aosaikang Pharmaceutical Co., Ltd. (“ASK”) for the Greater China Region and to JCOM, Ltd for South Korea. Under these agreements both of these partners will be conducting Phase 2 combination studies with ProLindac in specific tumor types at their expense based on these results. Access is currently in discussion with potential partners for development and commercialization of ProLindac in additional territories.

About ProLindac(TM):

ProLindac is a novel DACH platinum prodrug which has been shown to be active in a wide variety of solid tumors in both preclinical models and in human trials. Access believes that ProLindac’s unique molecular design potentially could eliminate some of the toxic side effects seen in the currently marketed DACH platinum, Eloxatin, which has sales in excess of $2 billion.

About Access:

Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access’ products include ProLindac(TM), currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard(TM) for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin(TM)-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism; Angiolix(R), a humanized monoclonal antibody which acts as an anti-angiogenesis factor and is targeted to breast cancer; Prodrax(R), a non-toxic prodrug which is activated in the hypoxic zones of solid tumors to kill cancer cells; Alchemix, a chemotherapeutic agent that combines multiple modes of action to overcome drug resistance. Access is also developing Phenylbutyrate (“PB”), an HDAC inhibitor and differentiating agent currently a Phase 2 clinical candidate. Access recently announced the acquisition of MacroChem Corporation. This acquisition provides Access with three additional late-stage product candidates. Pexiganan, a novel topical anti-infective for the treatment of diabetic foot infection, has already completed two Phase 3 trials. EcoNail is a topically applied econazole lacquer based on Access’ proprietary SEPA polymer technology, for the treatment of onychomycosis, a condition commonly known as nail fungus. Thiarabine is a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers. For additional information on Access Pharmaceuticals, please visit our website at www.accesspharma.com.

This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements include those relating to: clinical trial plans and timelines and clinical results for ProLindac and product candidates acquired in the MacroChem transaction, our ability to execute licensing agreements in the future, Access’ plans to continue and initiate clinical trials, the value of its products in the market, its ability to achieve clinical and commercial success and its ability to successfully develop marketed products. These statements are subject to numerous risks, including but not limited Access’ need to obtain additional financing in order to continue the clinical trial and operations and to the risks detailed in Access’ Annual Reports on Form 10-K and other reports filed by Access with the Securities and Exchange Commission.”

Quoted Source66% of evaluable heavily-pretreated patients in the high dose groups achieved disease stabilization. ProLindac was well tolerated, Press Release, lAccess Pharmaceuticals, Inc., March 5, 2009.

Evaluation of Neoadjuvant Chemotherapy and Debulking Followed by Intraperitoneal Chemotherapy in Women with Stage III and IV Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

It is well known that intraperitoneal (IP) chemotherapy prolongs survival in optimally cytoreduced (or debulked) ovarian cancer patients.  For patients who can not be optimally debulked, it is possible to administer neoadjuvant chemotherapy to place that patient in a position to be optimally debulked (i.e., 1 cm or less of residual disease post surgery) , thereby allowing the use of post-surgery IP chemotherapy (assuming optimal cytoreduction is achieved through surgery). This theory was tested in a Phase II clinical study (S0009) conducted by the Southwest Oncology Group (SOG). …

It is well known that intraperitoneal (IP) chemotherapy prolongs survival in optimally cytoreduced (or debulked) ovarian cancer patients.  For patients who can not be optimally debulked, it is possible to administer neoadjuvant chemotherapy to place that patient in a position to be optimally debulked (i.e., 1 cm or less of residual disease post surgery) , thereby allowing the use of post-surgery IP chemotherapy (assuming optimal cytoreduction is achieved through surgery). This theory was tested in a Phase II clinical study (S0009) conducted by the Southwest Oncology Group (SOG).

In SOG Study S009, researchers sought to evaluate overall survival (OS), progression-free survival (PFS), percentage of patients optimally debulked, and toxicity in Stage III/IV ovarian cancer patients treated with this strategy.

As part of the study, women with stage III/IV (pleural effusions only in stage IV) epithelial ovarian cancer, and fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous (IV) paclitaxel and carboplatin.  If, after neoadjuvant IV chemotherapy, the patient experienced a 50% or greater decrease in her CA125 tumor marker, cytoreduction surgery was performed.  If optimal debulking was achieved, the patient received IV paclitaxel, IP carboplatin and IP paclitaxel post-surgery.

The results of the study are set forth below.

  • 62 patients were registered for the study, of which four were ineligible.
  • 56 patients were evaluated for neoadjuvant chemotherapy toxicities. One patient died of pneumonia. Five patients had grade 4 toxicity, including neutropenia, anemia, leukopenia, anorexia, fatigue, muscle weakness, respiratory infection, and cardiac ischemia.
  • 36 patients received debulking surgery, and two patients had grade 4 hemorrhage.
  • 26 patients received post-cytoreduction chemotherapy. Four had grade 4 neutropenia.
  • At a median follow-up of 21 months, median PFS is 21 months and median OS is 32 months for all 58 patients.
  • PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months, respectively

The researchers performing the study concluded that the results compare favorably with other studies of sub-optimally debulked (i.e., >1 cm of residual disease post surgery) patients.

Primary SourcePhase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009; Tiersten AD, Liu PY, Smith HO et. al., Gynecol Oncol. 2009 Mar;112(3):444-9. Epub 2009 Jan 12.

What’s Feeding Cancer Cells? — Johns Hopkins Researchers Discover How Critical Cancer Gene Controls Nutrient Use.

“Cancer cells need a lot of nutrients to multiply and survive. While much is understood about how cancer cells use blood sugar to make energy, not much is known about how they get other nutrients. Now, researchers at the Johns Hopkins University School of Medicine have discovered how the Myc cancer-promoting gene uses microRNAs to control the use of glutamine, a major energy source. The results, which shed light on a new angle of cancer that might help scientists figure out a way to stop the disease, appear Feb. 15 online at Nature. …”

“February 15, 2009- Cancer cells need a lot of nutrients to multiply and survive. While much is understood about how cancer cells use blood sugar to make energy, not much is known about how they get other nutrients. Now, researchers at the Johns Hopkins University School of Medicine have discovered how the Myc cancer-promoting gene uses microRNAs to control the use of glutamine, a major energy source. The results, which shed light on a new angle of cancer that might help scientists figure out a way to stop the disease, appear Feb. 15 online at Nature.

Chi Dang, M.D., Ph.D. The Johns Hopkins Family Professor in Oncology Research; Professor of Medicine, Cell Biology, Oncology and Pathology; and Vice Dean for Research, School of Medicine

Chi Dang, M.D., Ph.D. The Johns Hopkins Family Professor in Oncology Research; Professor of Medicine, Cell Biology, Oncology and Pathology; and Vice Dean for Research, School of Medicine

‘While we were looking for how Myc promotes cancer growth, it was unexpected to find that Myc can increase use of glutamine by cancer cells,’ says Chi V. Dang, M.D., Ph.D., the Johns Hopkins Family Professor of Oncology at Johns Hopkins. ‘This surprising discovery only came about after scientists from several disciplines came together across Hopkins to collaborate — it was a real team effort.’

In their search to learn how Myc promotes cancer, the researchers teamed up with protein experts, and using human cancer cells with Myc turned on or off, they looked for proteins in the cell’s powerhouse — the mitochondria — that appeared to respond to Myc. They found eight proteins that were distinctly turned up in response to Myc.

At the top of the list of mitochondrial proteins that respond to Myc was glutaminase, or GLS, which, according to Dang, is the first enzyme that processes glutamine and feeds chemical reactions that make cellular energy. So the team then asked if removing GLS could stop or slow cancer cell growth. Compared to cancer cells with GLS, those lacking GLS grew much slower, which led the team to conclude that yes, GLS does affect cell growth stimulated by Myc.

The researchers then wanted to figure out how Myc enhances GLS protein expression. Because Myc can control and turn on genes, the team guessed that Myc might directly turn on the GLS gene, but they found that wasn’t the case. ‘So then we thought, maybe there’s an intermediary, maybe Myc controls something that in turn controls GLS,’ says Ping Gao, Ph.D., a research associate in hematology at Johns Hopkins.

They then built on previous work done with the McKusick-Nathans Institute of Genetic Medicine at Hopkins where they discovered that Myc turns down some microRNAs, small bits of RNA that can bind to and inhibit RNAs, which contain instructions for making proteins. The team looked more carefully at the GLS RNA and found that it could be bound and regulated by two microRNAs, called miR23a and miR23b, pointing to the microRNAs as the intermediary that links Myc to GLS expression.

‘Next we want to study GLS in mice to see if removing it can slow or stop cancer growth,’ says Gao. ‘If we know how cancer cells differ from normal cells in how they make energy and use nutrients, we can identify new pathways to target for designing drugs with fewer side effects.’

This study was funded by the National Institutes of Health, the National Cancer Institute, the Rita Allen Foundation, the Leukemia and Lymphoma Society and the Sol Goldman Center for Pancreatic Cancer Research.

Authors on the paper are Ping Gao, Irina Tchernyshyov, Tsung-Cheng Chang, Yun-Sil Lee, Karen Zeller, Angelo De Marzo, Jennifer Van Eyk, Joshua Mendell and Chi V. Dang, of Johns Hopkins; and Kayoko Kita and Takfumi Ochi of Teikyo University in Japan.

On the Web:
http://www.hopkinsmedicine.org/hematology/faculty_staff/dang.html
http://www.proteomics.jhu.edu/index.php
http://www.hopkinsmedicine.org/geneticmedicine/People/Faculty/mendell.html
http://www.nature.com/nature/index.html

– JHM –

Media Contacts: Audrey Huang; 410-614-5105; audrey@jhmi.edu
Maryalice Yakutchik; 443-287-2251; myakutc1@jhmi.edu

______________________

Quoted SourceWhat’s Feeding Cancer Cells? – Johns Hopkins Researchers Discover How Critical Cancer Gene Controls Nutrient Use, Press Release, Johns Hopkins Medicine, February 15, 2009.

Primary Citationc-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism; Ping Gao, Irina Tchernyshyov, Tsung-Cheng Chang et. al., Letter, Nature advance online publication 15 February 2009.

Physical Activity Preferences of Ovarian Cancer Survivors

The survey of ovarian cancer survivors was conducted in Alberta Canada and involved 359 participants.  Approximately 51% of the participants responded.  Over half expressed interest in participating in a physical activity program (53.8%).  The most common preferences found for physical activity included home-based programs (48.9%), post-treatment programs (69.5%), and walking programs (62.7%).

women-walkingIn a recent Canada study, the researchers conducted a survey regarding the interests and preferences of ovarian cancer survivors with regard to physical activity participation.  The survey of ovarian cancer survivors was conducted in Alberta Canada and involved 359 participants.  Approximately 51% of the participants responded.  Over half expressed interest in participating in a physical activity program (53.8%).

The most common preferences found for physical activity included home-based programs (48.9%), post-treatment programs (69.5%), and walking programs (62.7%).

The researchers also discovered that there were differences in preferences based on demographic, but not medical, factors.  Based on these findings, the researchers concluded that the majority of ovarian cancer survivors expressed interest in participating in physical activity programs; however, some preferences varied by demographic factors. The researchers also believe that designing physical activity interventions according to these preferences may optimize adherence and outcomes in ovarian cancer survivors.

Primary SourcePhysical activity preferences of ovarian cancer survivors; Stevinson C, Capstick V, Schepansky A. et. al., Psychooncology. 2009 Feb 26. [Epub ahead of print].

Do You Twitter? Tell Libby’s H*O*P*E* What You’re Doing!

Libby’s H*O*P*E*™ recently added a feed from its Twitter account (http://www.twitter.com/libbyshope) to the homepage left sidebar.  I know what you are thinking.  What in the heck is Twitter?

Twitter is a social networking  service that allows its users to send and read other users’ updates (known as “tweets”), which are text-based messages that cannot exceed 140 characters. Updates are displayed on the user’s profile page and delivered to other users who have signed up to receive them. Senders can restrict delivery to those in their circle of friends (delivery to everyone being the default). In addition, users can receive message updates via the Twitter website, mobile phone, Blackberry, etc.  It’s easy!  Set up a Twitter account and choose to follow “libbyshope.”  At this point, you will receive all Libby’s H*O*P*E*™ weblog updates no matter where you are located. You can perform a general search on the Twitter website for any topic (e.g., “cancer”) and you will find organizations and individuals who share your interest in that topic.

Twitter also allows you to send messages of 140 characters or less to Libby’s H*O*P*E*™.  In those messages, you can add web links to relevant news or medical articles and even include pictures. If you attend a cancer conference,  local hometown educational seminar or a fundraising event, you can send us brief comments (and pictures) directly from those events in real time.  Or, if you just feel like telling us how you are doing, that’s ok too!  Twitter allows cancer survivors to stay in touch with one through the communication of  valuable information and advice.

Currently, we are streaming Libby’s H*O*P*E*™ outbound twitter messages to our weblog (left homepage sidebar), but if the interest is high enough, we will stream all messages received and sent by Libby’s H*O*P*E*™ on the weblog.  By way of example, Libby’s H*O*P*E*™ is currently following the American Cancer Society, Association of Cancer Online Resources (ACOR), Cure Magazine, Lance Armstrong and several other cancer survivors and advocates.

The addition of Twitter to the Libby’s H*O*P*E*™ weblog is simply our way of allowing you to easily follow us regardless of your location.  More importantly, we hope to hear from many of you through this technology in the near future.  We provide below a video that describes “Twitter in plain English” and several additional links that will allow you to better understand Twitter.

Twitter in Plain English

Additional Resources:

  • Applications, Twitter.com. (we use twhirl as a desktop widget).
  • Tiny URL.com (application allows you to shorten any web address for inclusion in a Twitter message, thereby allowing you to minimize usage of the 140 character twitter message limit.

Fertility Treatments Unlikely to Raise Ovarian Cancer Risk

Ovarian cancer risk was no greater for women who used any of four different groups of fertility drugs [gonadotrophins, clomifenes, human chorionic gonadotrophin, and gonadotrophin releasing hormone] than for those who had not used these drugs. Of the ovarian cancer cases that did occur in this cohort, 58 percent were serous tumors—occurring in the outer lining of the ovary—and the incidence of this particular tumor type appears significantly higher only among women who had taken clomiphene, which was the most commonly used fertility drug.

“During the last few decades, women taking fertility drugs in order to become pregnant have not had definitive evidence that such treatments would not increase their ovarian cancer risk. Now researchers from Denmark, who conducted the largest population-based cohort study thus far to address this question, have reported that fertility drugs do not increase a woman’s risk of ovarian cancer. The study, led by Dr. Allan Jensen of the Institute of Cancer Epidemiology in Copenhagen, appeared February 5 in the British Medical Journal.

The study involved 54,362 Danish women who were treated in fertility clinics between 1963 and 1998 and then followed for a median of 15 years; 156 of these women eventually developed invasive epithelial ovarian cancer.

Ovarian cancer risk was no greater for women who used any of four different groups of fertility drugs [gonadotrophins, clomifenes, human chorionic gonadotrophin, and gonadotrophin releasing hormone] than for those who had not used these drugs. Of the ovarian cancer cases that did occur in this cohort, 58 percent were serous tumors—occurring in the outer lining of the ovary—and the incidence of this particular tumor type appears significantly higher only among women who had taken clomiphene, which was the most commonly used fertility drug. The authors noted that this association ‘may be real and important,’ but they pointed out that long-term follow-up studies will be needed to confirm this finding. Also, because the usual peak age for ovarian cancer diagnosis is 63 and the average age of these women was only 47 by the end of the study, they will continue to monitor the cohort.

Nevertheless, ‘Some women who take fertility drugs will inevitably develop ovarian cancer by chance alone,’ explained Dr. Penelope Webb in an accompanying editorial, ‘but current evidence suggests that women who use these drugs do not have an increased risk of developing ovarian cancer.’”

Quoted Source: Fertility Treatments Unlikely to Raise Ovarian Cancer Risk, NCI Cancer Bulletin Vol. 6 / No. 4, National Cancer Institute, February 24, 2009.

Primary Citations:

A Potential Treatment For Ovarian Cancer – Claudin-3 Gene Silencing Using Small Interfering RNA

“… Ovarian tumors highly express two proteins, claudin-3 and -4. These proteins are associated with both an increase is cellular motility and survival of ovarian tumor cells.  Claudin-3 is also over expressed in breast and prostate tumors. This new therapy is targeting claudin-3 (CLDN3) using small interfering RNA (siRNA). More specifically, this team has developed a nanoparticulate, lipid-like delivery system for intraperitoneal delivery of siRNA to ovarian tumors. Tests of the therapeutic efficacy of CLDN3 siRNA in three different mouse models showed a significant reduction in tumor growth.  Additionally, these mice showed no ill side effects of the CLDN3 siRNA treatment. …”

“PAPER REVEALS POTENTIAL NEW TREATMENT FOR OVARIAN CANCER

Wynnewood, PA, February 9, 2009 – – – – – Ovarian cancer is the fourth most common cancer in women and has the highest mortality rate for gynecologic cancers because it is often diagnosed at an advanced stage. New effective therapies for the treatment of advanced stage ovarian cancer are urgently needed.

Today, a paper published in the Proceedings of the National Academy of Sciences (PNAS) by Dr. Janet Sawicki, Professor at the Lankenau Institute for Medical Research (LIMR), a team headed by Daniel G. Anderson, Ph.D. and Robert Langer, Sc.D. of the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT) and David Bumcrot, Director of Research at Alnylam Pharmaceuticals, shows that a new therapy suppresses ovarian tumor growth and metastasis in preclinical studies.

Ovarian tumors highly express two proteins, claudin-3 and -4. These proteins are associated with both an increase is cellular motility and survival of ovarian tumor cells.  Claudin-3 is also over expressed in breast and prostate tumors. This new therapy is targeting claudin-3 (CLDN3) using small interfering RNA (siRNA). More specifically, this team has developed a nanoparticulate, lipid-like delivery system for intraperitoneal delivery of siRNA to ovarian tumors. Tests of the therapeutic efficacy of CLDN3 siRNA in three different mouse models showed a significant reduction in tumor growth.  Additionally, these mice showed no ill side effects of the CLDN3 siRNA treatment.

‘We are excited by the preclinical performance of these formulations, and are hopeful that the lipidoid-siRNA nanoparticulates developed here may enable new genetic therapies for ovarian cancer,’ said Anderson.

‘These findings offer new hope for a therapeutic treatment option for individuals with metastatic ovarian cancer and potentially other types of cancers that over-express CLDN3’, states Dr. Janet Sawicki.  ‘Our next step is to begin Phase I clinical trials to test for safety with hopes to bring this treatment to the patient in the next few years.’

This research was made possible through funding from the National Institutes of Health (NIH), the Sandy Rollman Ovarian Cancer Foundation of Havertown, PA, and Wawa.

Lankenau Institute for Medical Research
Founded in 1927, the Lankenau Institute for Medical Research (LIMR) is an independent, nonprofit biomedical research center located in suburban Philadelphia on the campus of the Lankenau Hospital. As part of the Main Line Health System, LIMR is one of the few freestanding, hospital-associated medical research centers in the nation.  The faculty and staff at the Institute are dedicated to advancing an understanding of the causes of cancer and heart disease. They use this information to help improve diagnosis and treatment of these diseases as well as find ways to prevent them. They are also committed to extending the boundaries of human health and well-being through technology transfer and education directed at the scientific, clinical, business and lay public communities. For more information visit: http://www.limr.org.

David H. Koch Institute for Integrative Cancer Research at MIT
Launched by MIT in 2008, the David H. Koch Institute for Integrative Cancer Research (KI) both transforms and transcends the Center for Cancer Research (CCR). CCR was founded in 1974 by Nobel Laureate and MIT Professor Salvador Luria, CCR has made enormous contributions to the field of cancer research. The Koch is one of only seven National Cancer Institute-designated basic research centers in the US and is comprised of faculty that have earned the most prestigious national and international science honors including the Nobel Prize and the National Medal of Science. For more information visit: web.mit.edu/ki/index.html.

Alnylam Pharmaceuticals, Inc.
Alnylam Pharmaceuticals, a leader in RNAi therapeutics, is a biopharmaceutical company developing novel therapeutics based on a breakthrough in biology known as RNA interference, or RNAi; a discovery that enables the creation of a broad new class of human therapeutics. Using RNAi, Alnylam has built a product engine to develop a deep pipeline of drug products to treat a wide array of important diseases. For more information visit: http://www.alnylam.com

Contact: Tava Shanchuk
Phone: (610) 645-3429
E-mail: shanchukt@mlhs.org”

RNA Interference Primer – Alnylam Pharmaceuticals

Quoted Source Paper Reveals Potential New Treatment for Ovarian Cancer, Press Release, Lankenau Institute for Medical Research, Feb. 9, 2009.

Primary CitationClaudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis; Huang YH, Bao Y, Peng W et. al., Proc Natl Acad Sci U S A. 2009 Feb 10. [Epub ahead of print]

Additional Resources: