Danbury Researchers Identify Markers in Treating Ovarian Cancer

Researchers may be one step closer to finding a cure for ovarian cancer! Researchers at the Danbury Hospital Biomedical Research Institute recently discovered two proteins as markers of response to neoadjuvant chemotherapy for ovarian cancer. Read more about the exciting discovery in the article below:

Researchers from the Danbury Hospital Biomedical Research Institute have discovered that high expression levels of two proteins - HGF and c-MET - are present in women with ovarian cancer who did not benefit from undergoing tumor-shrinking chemotherapy prior to having surgery to remove their tumor.

Marisa Mariani, PhD, of Danbury Hospital Biomedical Research Institute, and colleagues, who published their results in OncoTarget, made this discovery using a two-pronged approach that first explored possible markers of chemotherapy resistance at the microRNA and gene expression level, and then validated any markers of interest at the protein level. 

"This approach is important because if you are eventually going to use a drug to target these markers, the drug will target the protein and not the gene," Dr. Mariani said. "We had to confirm that what we were seeing at the gene level lead to a change at the protein level."

Ovarian cancer is the leading cause of death for gynecologic malignancies. About 85 percent of women who are diagnosed in the advanced stage of the disease will die. Women with advanced disease may sometimes undergo chemotherapy prior to surgery, called neoadjuvant chemotherapy, in an attempt to shrink the tumor.

Exposing the tumor to chemotherapy prior to surgery gave Dr. Mariani and colleagues a unique opportunity to investigate the biology of the tumor's response to chemotherapy. Using tumor samples taken from patients with ovarian cancer after neoadjuvant chemotherapy, they discovered several prevalent microRNAs, the presence of which demonstrated an ability to survive even after exposure to chemotherapy. Among the discovered microRNA miR-193a-5p was the most significant.

MicroRNA regulates the expression of genes. Therefore, the researchers next conducted an analysis to determine the targets of miR-193a-5p and found that two genes, HGF and cMET, were significantly correlated with the microRNA.

Finally, the researchers used quantitative fluorescent immunohistochemistry to conduct a protein analysis. Once again they found that protein expression levels of HGF and cMET expression were significantly increased in patients after undergoing neoadjuvant chemotherapy. In fact, patients who relapsed shortly after neoadjuvant chemotherapy had the highest levels of HGF and cMET and those patients who responded best to the treatment had the lowest expression levels.

"This type of discovery is very important because if patients undergo neoadjuvant chemotherapy and the treatment has no effect, then it is often too late to perform surgery because the cancer has progressed," said senior author Cristiano Ferlini, MD, PhD, also from Danbury Hospital Biomedical Research Institute. "This can help us to know upfront that these patients may not benefit from neoadjuvant therapy and can prevent them from undergoing this unnecessary treatment."

According to Dr. Ferlini, the Danbury Hospital Biomedical Research Institute will continue to embrace cutting-edge technology, working to uncover biomarkers that will help clinicians to more appropriately select therapies for patients with cancer.

"Even though we are a small organization we have been very successful operating at the border between clinical and basic research," Dr. Ferlini said. "We are motivated to learn from our patients at the bedside and get back to the bedside as quickly as possible with new treatment options."

Click the link to read the full article from Danbury Patch: http://aol.it/1s85B4Q

Mercy Medical Center in Baltimore is Raising the Heat on Ovarian Cancer

A lot of doctors get fired up over ovarian cancer treatment, but the oncologists at Mercy Medical Center in Baltimore are taking it to a whole new level. According to a recent news article from 8-News Now in Las Vegas, these doctors are using a new and aggressive treatment called HIPEC, an abbreviation for hyperthermic interperitoneal chemotherapy, in which doctors first remove all traces of the tumor along with several other organs, if necessary. Then a catheter is inserted which delivers heated chemotherapy. The function of the heat is two-fold: it kills cancer cells but also enhances the effects of chemotherapy. The chemo temperature of the chemo reaches about 109 degrees Fahrenheit and circulates in the patient for 90 minutes. HIPEC is being studied as a first-line therapy for ovarian cancer patients in a phase-two trial. Of the new treatment, Dr. Teresa Diaz-Montes, Gynecologic Oncologist at Mercy Medical Center, said, “We are trying to see if we can be more proactive in preventing more women from recurring.”

The article also explains how HIPEC is different from other forms of ovarian cancer treatment: “Systemic chemotherapy delivery circulates throughout the body. The HIPEC treatment is different because it delivers to cancer cells in the abdomen. This allows for higher doses of chemotherapy. The heat can also improve how the tumors absorb the drugs. It can destroy microscopic cancer cells that remain in the abdomen after surgery.”

Chief of Surgical Oncology Dr. Armando Sardi recently used this new approach on Helen Szablya, who was diagnosed with cancer five years ago. Her tumor was so big that doctors couldn’t even see her ovaries. Her particular type of cancer (primary peritoneal carcinoma, which is very similar to epithelial ovarian cancer) was so serious that Szablya and her husband, Charles Dann, weren’t sure they’d make it to their 20th wedding anniversary.

Szablya received HIPEC from Dr. Sardi and has been cancer-free for five years. “It saves your life!” she said of the treatment. Her husband added, “It’s really quite amazing to understand what Helen has gone through and what amazing odds she’s overcome.”

Read the full story from 8-News Now KLAS-TV Las Vegas.

Know Your Options

If you find out you have the BRCA gene, do not think that surgery is your only option.  There are many ways to reduce the risk of ovarian cancer.  Research has found that breast feeding, birth control pills, and having fallopian tubes tied all may help reduce the risk of ovarian cancer.  Learn more in the article below and always remember to talk with your doctor before making any decisions.  You can learn more here.

Breast-feeding, birth control pills and having fallopian tubes tied may help reduce ovarian cancer risk in women with BRCA gene mutations, a new review suggests.

Women with BRCA gene mutations are at increased risk for breast and ovarian cancers. These findings suggest ways that women with these inherited mutations can reduce their ovarian cancer risk without having their ovaries surgically removed, the University of Pennsylvania researchers said.

“Patients deserve better cancer-risk reduction options than surgically removing their healthy breasts and ovaries,” review co-author Dr. Susan Domchek, executive director of the Basser Research Center for BRCA at Penn Medicine’s Abramson Cancer Center, said in a university news release.

Domchek and her colleagues reviewed 44 studies and found that breast-feeding and tubal ligation were associated with lower rates of ovarian cancer in women with a BRCA1 mutation, while the use of birth control pills was associated with a reduced risk of ovarian cancer in women with BRCA1 or BRCA2 mutations.

The researchers also identified factors that may increase the risk of cancer in women with BRCA mutations. For example, smoking may heighten the risk of breast cancer in women with a BRCA 2 mutation.

The findings are to be published in the June issue of the Journal of the National Cancer Institute.

“Our analysis reveals that heredity is not destiny, and that working with their physicians and counselors, women with BRCA mutations can take proactive steps that may reduce their risk of being diagnosed with ovarian cancer,” lead author Timothy Rebbeck, professor of epidemiology and cancer epidemiology and risk reduction program leader at the Abramson Cancer Center, said in the news release.

“The results of the analysis show that there is already sufficient information indicating how some variables might affect the risk of cancer for these patients,” he added.

About 39 percent of women with a harmful BRCA1 mutation and up to 17 percent of those with a harmful BRCA2 mutation will develop ovarian cancer by age 70, compared with 1.4 percent of women in the general population.

Between 55 percent and 65 percent of women with a harmful BRCA1 mutation and 45 percent of women with a harmful BRCA2 mutation will develop breast cancer by age 70, compared with about 12 percent of women in the general population.

Both BRCA mutations have also been linked with increased risk for several other types of cancer, according to the researchers.

“It’s imperative that we continue examining and building upon past research in this area so that we can provide BRCA mutation carriers with options at every age, and at every stage of their lives,” Domchek noted.