Genetic Analysis Indicates Ovarian Cancer May Originate In Fallopian Tubes

Genetic Analysis Indicates Ovarian Cancer May Originate In Fallopian TubesMany of the most severe ovarian cancer cases may originate in the fallopian tube (FT), based on data from an analysis of nine patients published online in Nature Communications.

“Our data suggest that FT neoplasia is the origin of ovarian serous carcinogenesis, and can directly lead to cancer of the ovaries and of other sites,” wrote Sana Intidhar Labidi-Galy, MD, of Dana-Farber Cancer Institute, Boston, and her colleagues (Nature Commun. 2017 Oct 23. doi: 10.1038/s41467-017-00962-1).

Preliminary evidence suggests that fallopian tube cancers may develop into high-grade serous ovarian carcinoma (HGSOC), but evolutionary evidence is limited, the researchers said.

They conducted genetic sequencing on 37 tumor samples from five adult patients with HGSOC. They identified changes in the TP53 tumor suppressor gene in all cases of HGSOC. They also studied serous tubal intraepithelial carcinomas from four patients.

“As expected, we identified sequence changes in the TP53 tumor suppressor gene, a well-known driver gene in HGSOC, in all cases,” the researchers wrote.

“The TP53 alterations were identical in all samples analyzed for each patient including in the p53 signatures, the [serous tubal intraepithelial carcinoma] lesions, and other carcinomas,” Dr. Labidi-Galy and her associates said. Although TP53 was the only gene analyzed in this study, the researchers also noted changes in areas of several known ovarian cancer genes, including BRCA1 and BRCA2.

The study findings were limited by the small size of the tumor samples and small number of cells, the researchers noted.

The results, however, suggest an avenue for further research to help guide early detection and treatment of ovarian cancer, such as the potential removal of fallopian tubes rather than the ovaries in some cases, they concluded.

The research was supported by multiple foundations and organizations, including the National Institutes of Health. One of the investigators is a founder of Personal Genome Diagnostics and a member of its scientific advisory board and board of directors. The other researchers had no financial conflicts to disclose.

To read this full article on Ob.Gyn.News., please click here.


To Prevent Ovarian Cancer, Focus on the Fallopian Tube

To Prevent Ovarian Cancer, Focus on the Fallopian TubeMounting evidence suggests that most, if not all, serous ovarian cancers start in the fallopian tubes, not in the ovaries.

Using integrated molecular genomics, researchers confirm and extend prior research showing that high-grade serous carcinomas (HGSCs) in the pelvis are preceded by serous tubal intraepithelial carcinoma (STIC) lesions occurring in the fallopian tubes.

“Based on a better understanding of its origins, our study suggests new strategies for the prevention and early detection of ovarian cancer,” senior investigator, Douglas Levine, MD, director, Division of Gynecologic Oncology, Perlmutter Cancer Center at NYU Langone Health in New York City, said in a news release.

The study was published online October 17 in Nature Communications.

For decades it was thought that ovarian cancer originates in the ovarian surface epithelium or cortical inclusion cysts. But recent data suggest that HGSC of the pelvis likely originates from the epithelium of the distal portion of the fallopian tube. STIC lesions, the putative precursor to HGSC, have been found in the fallopian tube and in about half of advanced-stage HGSCs.

To better understand the molecular cause of HGSC, Dr Levine and colleagues analyzed 96 HGSCs, half with a STIC lesion and half without a STIC lesion.

“Usually cancers that begin from different anatomic sites have different genomic profiles,” Dr Levine noted in an interview with Medscape Medical News. “What this study showed using multiple integrated approaches is that HGSCs all seem to have similar molecular profiles that cannot be easily distinguished. That suggests that the site of origin is shared and the most common biologic explanation would be in the fallopian tube,” he said.

In their analysis, HGSC cases with and without STIC lesions shared the most significant focal DNA somatic copy number alterations.  “We found no differences in the 20,000 genes that we can identify. This leads us to believe that these ovarian cancers all originate in the fallopian tubes,” said Dr Levine.

In addition, RNA sequence and microRNA failed to identify any clear separation between cases with and without STIC lesions.  HGSCs had molecular profiles more similar to normal fallopian tube epithelium than to ovarian surface epithelium or peritoneum.

A Practice-Changing Paradigm Shift

The data support the rationale to focus on the distal fallopian tube when surgical or medical approaches to prevent HGSC are being considered, the researchers say.

“This whole paradigm shift that ovarian cancers start in the fallopian tubes is already changing practice,” Dr Levine told Medscape Medical News.

He further explained: “We now take out the fallopian tubes when it’s convenient to do so. Many patients have their tubes tied for contraceptive purposes, which works. But if you take the tubes out, that also works, and it may help to prevent ovarian cancer. In very select situations — women who are at very high risk for ovarian cancer — our recommendation at the appropriate age is to have the ovaries and fallopian tubes removed.”

The findings also have implications for early detection of ovarian tumors. If biomarkers can be found for these tubal cells, future blood tests, advanced Papanicolaou (Pap) smears, or direct tests on tubal tissue might be able to detect ovarian cancer earlier, the researchers say.

“Now that we believe that ovarian cancer comes from the fallopian tubes, the question is, could something like a Pap smear detect DNA mutations or protein fragments? Because the fallopian tubes are connected to the cervix and the vagina, we can get very close to them, and proteins and biomarkers can flow between these structures quite easily,” Dr Levine told Medscape Medical News.

Reached for comment, Jamie Bakkum-Gamez, MD, Mayo Clinic, Rochester, Minnesota, said, “This is a very interesting study and as a gynecologic oncologist it definitely makes a lot of sense. This study helps us have a greater understanding that all serous cancers and invasive cancers look very similar whether there is a STIC in the fallopian tube or not.”

“We already believe that the tube is where serous ovarian cancers start.  This study is a nice molecular validation of what we think is happening,” said Dr Bakkum-Gamez.  Currently, she added, “in a lot of practices, when we are doing a hysterectomy for benign indications and leaving the ovaries, we are taking out the fallopian tubes and that is based on the original histopathology data that shows that at least 50% of serous cancers have some sort of STIC lesion associated with them.”

“For practices that aren’t doing incidental salpingectomy in average-risk women, this is mounting evidence to help support that procedure,” she advised.

To read this full article on Medscape, please click here.

Ovarian Cancer Gene Therapy Specialist Is One of Three Researchers Sharing $1.3 Million in Grants

Ovarian Cancer Gene Therapy Specialist Is One of Three Researchers Sharing $1.3 Million in GrantsThree American scientists have received $1.3 million from the Alliance for Cancer Gene Therapy to investigate whether immunotherapy and gene therapy can combat three of the most life-threatening forms of cancer: ovarian, brain and bone cancer.

The three are Drs. Daniel Powell Jr. of the University of Pennsylvania’s Perelman School of Medicine, Nori Kasahara of the University of Miami’s Sylvester Comprehensive Cancer Center, and Seth Pollack of Seattle’s Fred Hutchinson Cancer Research Center.

“We have big hopes for these grants,” John Walter, the alliance’s president and chief executive officer, said in a press release. “The recent FDA approval of the first gene therapy treatment to come out of this research, Kymriah, validates the promise of this science. With these three new clinical investigator grants, we hope to see similar results with immunotherapy and virotherapy [virus-based therapies] in treating hard-to-combat solid tumor cancers.”

Powell will work on CAR T-cell therapies for ovarian cancer. He will use his grant to enroll nine patients in a new clinical trial of the treatment. CAR T-cell therapy involves gathering a patient’s own immune T-cells, engineering them in a lab to recognize cancer cells, then reintroducing them to the patient. The full scientific name for CAR T-cells is chimeric antigen receptor T-cells.

Kasahara will investigate viral therapies for brain cancer, or glioblastoma, and Pollack immunotherapies  against bone cancer, or sarcoma.

The Alliance for Cancer Gene Therapy grants will allow “these scientists to advance their research from the laboratory to the bedside for patients in clinical trials, providing for an opportunity to see these treatments work in actual patients and hopefully save lives,” Walter said. The organization’s goal “is to truly make an impact on how cancer is treated through the use of gene and cell therapies, so that one day cancer will be a treatable and manageable disease.”

The alliance is the only U.S. organization dedicated exclusively to funding cell and gene therapy cancer research. It has made 55 grants totaling more than $28 million since its inception in 2001.

To read this full article on Ovarian Cancer News Today, please click here.

In Early Study, Rare Tumors Respond To Precision Therapy

By: Bradley J. Fikes

In Early Study, Rare Tumors Respond To Precision TherapyTreatment of rare tumors can be improved with a “precision medicine” approach of matching treatment to the molecular profile of the cancers, according to a preliminary study from UC San Diego researchers.

Tumors stabilized, regressed or disappeared entirely in 11 of 21 patients given the matched therapy, according to a paper on the study published Monday in The Oncologist.

The improvement persisted for six months or longer, and was significantly longer than the last previous unmatched therapy given to the patients, the paper stated.

“Further studies investigating the efficacy of the precision therapy approach among rare tumors are warranted,” it concluded.

The researchers examined 40 patients with rare tumors to see if their cancers could be matched with a precision therapy based on analyzing the genetic and protein makeup of the tumors. Just over half received matched therapy.

The paper can be found at when placed online. Razelle Kurzrock was senior author; the first author was Shumei Kato.

The study is based on the experience of a Rare Tumor Clinic recently established at UCSD Moores Cancer Center to deal with these difficult cases. Rare tumors in the study patients included two types of ovarian cancer, basal cell carcinoma and sarcoma.

Because these tumors are rare, doctors often lack experience dealing with them, including making the diagnosis. Moreover, there’s often a lack of therapies approved for these particular cancers.

A rare kind of tumor occurs in fewer than 15 cases per 100,000 people. The total incidence of cancer in the United States is about 455 new cases annually per 100,000, according to the National Cancer Institute.

However, when added together, rare cancers are collectively not that uncommon, representing nearly 25 percent of cancer cases. That amounts to a considerable proportion of cancers that don’t have adequate treatment options, the study said.

Tumor-matching is also carried out by the San Diego-based Clearity Foundation for women with recurrent ovarian cancer. The foundation provides a “tumor blueprint” with the cancer’s molecular characteristics, which is used to select a treatment regimen for the particular tumor.

The study was supported by the Joan and Irwin Jacobs Fund and the National Cancer Institute.

To read this entire article by The San Diego Union Tribune, please click here.

Webinar: PARP Inhibitors: What You Need to Know

Join OCRFA on Monday, Oct. 23rd at 6:00pm ET for a webinar on PARP Inhibitors with Dr. Ursula Matulonis of Dana-Farber Cancer Institute.

Webinar: PARP Inhibitors: What You Need to KnowThere is a great amount of excitement in the ovarian cancer clinical and research communities about the approval of three PARP inhibitors for treatment and maintenance therapy for ovarian cancer. Dr. Matulonis will provide an overview of these new treatments: how they are used now, how they are different from each other, and how they may be used in the future, and will answer your questions.

About the Speaker: Ursula A. Matulonis, MD
Dr. Matulonis, is Medical Director and Disease Center Leader of the Medical Gynecologic Oncology Program at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. Her research focuses on developing new targeted therapies for gynecologic malignancies, with a specific interest in the genetic changes in ovarian cancer and how that can lead to rationale drug selection.

Dr. Matulonis is Principal Investigator (PI) of several clinical trials and translational studies for ovarian cancer. She is the PI of a Department of Defense grant on ovarian cancer entitled “Prediction of Response to Therapy and Clinical Outcome Through a Pilot Study of Complete Genetic Assessment of Ovarian Cancer” and a Co-PI on the project “Genetic similarities between serous ovarian cancer and triple negative breast cancer” funded by the Breast Cancer Research Foundation. Dr. Matulonis serves on the National Comprehensive Cancer Network Recommendation and Guideline committee for both ovarian cancer and for the treatment of anemia, the Gynecologic Oncology Group ovarian committee and quality of life committee, the National Cancer Institute Ovarian Cancer Task Force, and is Medical Director and Board Member for the non-profit organization Ovations for the Cure. She is a recipient of the Dennis Thompson Compassionate Care Scholar award, the Lee M. Nadler “Extra Mile” Award, the Zakim Award for patient advocacy and has been named one of Boston’s Best Physicians in Medical Oncology by Boston Magazine.

Date and time: Monday, October 23, 2017 6:00 pm (Eastern Daylight Time)

Duration: 1 hour

Register: Click here!

Ultra-Personal Therapy: Gene Tumor Boards Guide Cancer Care

By: Marilynn Marchione

Ultra-Personal Therapy: Gene Tumor Boards Guide Cancer CareDoctors were just guessing a decade ago when they gave Alison Cairnes’ husband a new drug they hoped would shrink his lung tumors. Now she takes it too, but the choice was no guesswork. Sophisticated gene tests suggested it would fight her gastric cancer, and they were right.

Cancer patients increasingly are having their care guided by gene tumor boards, a new version of the hospital panels that traditionally decided whether surgery, radiation or chemotherapy would be best. These experts study the patient’s cancer genes and match treatments to mutations that seem to drive the disease.

“We dissect the patient’s tumor with what I call the molecular microscope,” said Dr. Razelle Kurzrock, who started a board at the University of California, San Diego, where Cairnes is treated.

It’s the kind of care many experts say we should aim for — precision medicine, the right drug for the right person at the right time, guided by genes. There are success stories, but also some failures and many questions:

Will gene-guided care improve survival? Does it save money or cost more? What kind of gene testing is best, and who should get it?

“I think every patient needs it,” especially if cancer is advanced, said Kurzrock, who consults for some gene-medicine companies. “Most people don’t agree with me — yet. In five years, it may be malpractice not to do genomics.”

Few people get precision medicine today, said Dr. Eric Topol, head of the Scripps Translational Science Institute. “The only thing that’s gone mainstream are the words.”


If you have a cancer that might be susceptible to a gene-targeting drug, you may be tested for mutations in that gene, such as HER2 for breast cancer. Some breast or prostate cancer patients also might get a multi-gene test to gauge how aggressive treatment should be.

Then most patients get usual guideline-based treatments. If there’s no clear choice, or if the disease has spread or comes back, doctors may suggest tumor profiling — comprehensive tests to see what mutations dominate.

That’s traditionally been done from a tissue sample, but newer tests that detect tumor DNA in blood — liquid biopsies — are making profiling more common. The tests cost about $6,000 and many insurers consider them experimental and won’t pay.

Gene tumor boards analyze what the results suggest about treatment. They focus on oddball cases like a breast cancer mutation in a colon cancer patient, or cancers that have widely spread and are genetically complex. The only options may be experimental drugs or “off-label” treatments — medicines approved for different situations.

But as tumor profiling grows, it’s revealing how genetically diverse many tumors are, and that oddball cases are not so rare, said Dr. John Marshall. He heads the virtual tumor board at Georgetown Lombardi Comprehensive Cancer Center that also serves cancer centers in Pennsylvania, North Carolina, Michigan and Tennessee.

“There is a little bit of faith” that testing will show the right treatment, but it’s not a sure thing, said Dr. Lee Schwartzberg, who heads one participating center, the West Cancer Center in Memphis.

Dr. Len Lichtenfeld, the American Cancer Society’s deputy chief medical officer, is optimistic yet wary. Drugs that target BRAF mutations work well for skin cancers called melanomas, but less well for lung or colon cancers.

“Just because a mutation occurs it doesn’t mean that drug is going to work in that cancer,” he said.


When it does, results can be dramatic. Cairnes’ cancer was between her stomach and esophagus, and had spread to her liver, lungs and lymph nodes. Tissue testing found 10 abnormal genes, but on the liquid biopsy only EGFR popped out as a good target.

The drugs Tarceva and Erbitux aim at that gene but aren’t approved for her type of cancer. A tumor board advised trying the combo. Within two weeks, she quit using pain medicines. After two months, her liver tumor had shrunk roughly by half. There are signs that cancer may remain, but it is under control. She feels well enough to travel and to take care of her granddaughter.

“I’m very, very grateful to have a targeted therapy,” Cairnes said.

“I cannot expect a better outcome than what we’re seeing right now,” said her doctor, Shumei Kato.


But is gene-guided treatment better than usual care? French doctors did the first big test, with disappointing results. About 200 patients with advanced cancer were given whatever their doctors thought best or off-label drugs based on tumor profiling. Survival was similar — about two months.

Another French study, reported in June, was slightly more encouraging on survival but exposed another problem: No drugs exist for many gene flaws. Tests found treatable mutations in half of the 2,000 participants and only 143 got what a tumor board suggested.

Some doctors worry that tumor boards’ recommending off-label treatments diverts patients from research that would benefit all cancer patients. For example, the American Society of Clinical Oncology’s TAPUR study tests off-label drugs and shares results with their makers and federal regulators.


Ann Meffert, who lives on a dairy farm in Waunakee, Wisconsin, endured multiple standard treatments that didn’t defeat her bile duct cancer.

“She was going to be referred to hospice; there was not much we could do,” said Dr. Nataliya Uboha, who took the case to a tumor board at the University of Wisconsin-Madison. The panel gave several options, including off-label treatment, and Meffert chose a study that matches patients to gene-targeting therapies and started on an experimental one last October.

“Two weeks in, I started feeling better,” she said, and when she saw test results, “I couldn’t believe the difference.”

Many lung spots disappeared and the liver tumor shrank 75 percent. She is not cured, though, and doctors are thinking about next steps. And that could involve a fresh look at her tumor genes.

To read this full article by The Washington Post, please click here.

Most Ovarian Cancers Start In The Fallopian Tubes, Study Finds

Most Ovarian Cancers Start In The Fallopian Tubes, Study FindsMost – and possibly all – ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

This is the finding of a multicenter study of ovarian cancer genetics led by researchers from Perlmutter Cancer Center at NYU Langone Health, and published online Oct. 17 in Nature Communications.

“Based on a better understanding of its origins, our study suggests new strategies for the prevention and early detection of ovarian cancer,” says senior study author Douglas A. Levine, MD, director of the Division of Gynecologic Oncology at Perlmutter and professor of Obstetrics and Gynecology at NYU School of Medicine.

The results revolve around the fallopian tubes, which enable egg cells that have the potential to be fertilized and become embryos – to pass from the ovaries where they are made to the uterus. The new study found that ovarian cancer cells have more in common with cells covering the tips of fallopian tubes than with those on the surface of ovaries.

If biomarkers can be found for these tubal cells, say the authors, future blood tests, advanced Pap smears, or direct tests on tubal tissue might be able to detect ovarian cancer earlier. The research team plans to conduct studies that will seek to apply the current molecular biology findings to clinical practice, but Levine says it may take years to prove that this approach detects ovarian cancer earlier, prevents its spread, or extends survival in patients with this disease.

The new findings also point to the possibility that removing a woman’s fallopian tubes, but not her ovaries, may reduce risk of ovarian cancer in those at high risk for disease, including those with genetic changes (mutations) known to increase risk (e.g. BRCA).

“We are one of several centers taking part in Women Choosing Surgical Prevention or WISP trial, which seeks to determine whether removing the tubes improves quality of life, compared to removing both the tubes and ovaries,” Levine says.

Also not yet clear is whether or not the cells that become ovarian cancer become malignant in the fallopian tubes or if they circulate to other organs first. If it is the latter, then removing the fallopian tubes might not work. It is also possible that some ovarian cancers originate elsewhere, says Levine.

Despite the remaining uncertainties, the current study does confirm previous results that had suggested that many high-grade serious cancers in the pelvis are preceded by abnormal cells (lesions) occurring in the fallopian tubes, called serous tubal intraepithelial carcinoma (STIC).

Past studies in several cancer types had shown that cancer cells with different origins have different genetic profiles. Cancer cells may arise from nearby tissue or may have spread to a location from another part of the body, but their genetic profile reflects the tissue of origin.

Thus, the researchers knew going in that if STIC cells and ovarian cancer cells had different genetic profiles, they must have originated in different tissue types. Instead, in-depth molecular analyses of cells from 96 women with high-grade serous carcinoma failed to identify any genetic differences between cancer cells arising in the tubes and serous “ovarian” cancers occurring elsewhere in the pelvis.

“We found no differences in the 20,000 genes that we can identify,” says Levine. “This leads us to believe that that these ovarian cancers all originate in the fallopian tubes.”

Ovarian cancer is more aggressive than many other cancers because it is hard to diagnose in its earliest – and most treatable – stages. Fewer than 50 percent of women diagnosed with the disease survive for longer than five years after their diagnoses, according to the American Cancer Society.

To read this full article on News Medical Life Sciences, please click here.