Posts tagged ‘Ovarian cancer’
Chemotherapy drugs work by either killing cancer cells or by stopping them from multiplying, that is, dividing. Some of the more powerful drugs used to treat cancer do their job by interfering with the cancer cells’ DNA and RNA growth, preventing them from copying themselves and dividing.
Such drugs, however, like Hydroxyurea, do have drawbacks. One is that the body metabolizes them quickly. Patients need frequent doses to achieve the desired effects. Because the side effects of the drugs are already considerable, increased use of them raises the risk of negative reactions. Another drawback is that cancer cells develop rapid resistance to the drugs, reducing their effectiveness.
A team effort
As a physician, molecular pharmacologist Yun Yen, M.D., Ph.D., knows well the limitations of chemotherapy drugs. He partnered with medicinal chemist David Horne, Ph.D., to find — and improve — a molecule, or compound, to overcome these problems.
First, Yen selected a promising anti-cancer compound from the National Cancer Institute’s library of anti-cancer agents. Then, using data obtained with the help of the skilled laboratory scientists in City of Hope’s Core (or “Shared”) Services, Horne began to make structural adjustments to improve the molecule’s effectiveness. Core Services provides researchers, specialized expertise, testing and instrumentation in fields such as molecular modeling, screening, medicinal chemistry and cancer biology. Access to these services enabled Yen and Horne to determine, even before preclinical testing, how the compound worked. » Continue Reading
Ryan Chavira was a senior in high school when she began feeling sluggish, fatigued and, well, “down.” Trips to the doctor ended in “you’re fine” pronouncements; blood tests results showed nothing of real concern.
But Chavira’s grandmother had passed away from ovarian cancer when she was in eighth grade, and the distended stomach and bloated feeling that Chavira was experiencing reminded her of her grandmother’s symptoms.
When the bloating gave way to pain, then excruciating pain, Chavira went to a hospital emergency room. A CT scan revealed a tumor the size of a watermelon engulfing her ovaries. Emergency surgery was the only option.
Chavira, now 22, describes the diagnosis and decision on a course of action in this way: “They come in, say ‘You have cancer and we’ll be right back to operate.’” There was no time for the diagnosis to sink in. » Continue Reading
Immunotherapy — using one’s immune system to treat a disease — has been long lauded as the “magic bullet” of cancer treatments, one that can be more effective than the conventional therapies of surgery, radiation or chemotherapy. One specific type of immunotherapy, called adoptive T cell therapy, is demonstrating promising results for blood cancers and may have potential against other types of cancers, too.
Here, Leslie Popplewell, M.D., associate clinical professor and staff physician in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation, explains what this treatment entails.
What is adoptive T cell therapy and how does it work to treat cancer?
Every day, our immune system works to recognize and destroy abnormal, mutated cells. But the abnormal cells that eventually become cancer are the ones that slip past this defense system. The idea behind this therapy is to make immune cells (specifically, T lymphocytes) sensitive to cancer-specific abnormalities so that malignant cells can be targeted and attacked throughout the body.
Who would be good candidates for this type of therapy? » Continue Reading
For women with ovarian cancer, the results of recent study could mean new hope for future treatments. The findings, reported at the American Society of Clinical Oncology’s annual meeting, found that a combination of two experimental drugs, olaparib and cediranib, significantly lengthened the duration of progression-free survival compared to olaparib alone and standard chemotherapy.
The phase II trial is the first time that a PARP inhibitor is combined with an anti-angiogenic drug to treat ovarian cancer. PARP inhibitors such as oliparib work by thwarting cancer cells’ ability to repair their own DNA, while anti-angiogenic drugs such as cediranib halts growth of new blood vessels in tumors.
“The significant activity that we saw with the combination suggests that this could potentially be an effective alternative to standard chemotherapy,” said the study’s lead author Joyce Liu, M.D., M.P.H., in a press release.
Liu, an instructor in medical oncology at Dana Farber Cancer Institute, added that these findings showed that the two drugs worked synergistically and bolstered each other’s effectiveness against the cancer.
For this clinical trial, Liu and her colleagues randomized 90 patients with recurrent, platinum-sensitive ovarian cancer into either olaparib-only or olaparib+cediranib groups. In their analysis, they found that progression-free survival was significantly higher in the combination group, over 17 months compared to nine months in oliparib only. Meanwhile, previous trials with standard chemotherapy in this population showed a progression-free survival range from eight to 13 months.
More than 18,000 researchers, clinicians, advocates and other professionals will convene at the 105th American Association for Cancer Research (AACR) annual meeting taking place in San Diego from April 5 to 9. With more than 6,000 findings being presented over this five-day period, the amount of information can seem overwhelming.
But all those posters, presentations and seminars serve a purpose, which is best summed up by the theme of this year’s meeting: “Harnessing Breakthroughs –Targeting Cures.”
“We are in the generation of personalized, precision medicine where we can learn a great deal about cancers,” said Steven T. Rosen, M.D., City of Hope’s Irell & Manella Cancer Center Director’s Distinguished Chair. “Conferences such as AACR’s annual meeting lead to true dialogue, exchange of information and collaboration. This not only benefits the scientists’ own research projects, but also leads to meaningful advances for treating, detecting and preventing cancers.”
Added Rosen, who is also City of Hope’s provost and chief scientific officer: “City of Hope investigators are well-represented at this year’s annual meeting. They have made significant contributions to our understanding of cancers. This includes furthering our knowledge of individual cancers’ epidemiology and etiology, developing novel therapies and enhancing survivorship.”
The findings and knowledge that City of Hope researchers are sharing at this year’s conference include: » Continue Reading
A phase I clinical trial led by researchers at City of Hope has demonstrated the promise of a new drug combination for women with triple-negative breast cancer.
This type of breast cancer doesn’t produce any of the three proteins that common cancer therapies target — the identifying characteristic that gives it its name, and which makes it especially difficult to treat. The trial, led by Jeffrey Weitzel, M.D., and George Somlo, M.D., both professors of medical oncology and therapeutics research, tests the common drug carboplatin in combination with a novel targeted therapy called a PARP inhibitor. » Continue Reading
In this series, we explore crucial strides made against women’s cancers by City of Hope researchers during the past year. The projects are many and varied, involving the basics of fighting cancer, analyses of who’s at greatest risk, the search for surprising new therapies, the testing of new treatments and the follow-up with survivors and their partners.
Advances in immunotherapy
Peter P. Lee, M.D., chair of cancer immunotherapeutics and tumor immunology at City of Hope, is pursuing several projects that are part of a what he calls integrated immunotherapy. This concept advances the idea that effective cancer treatment must address each phase or action of the body’s complex immune system. » Continue Reading
Despite vitamin C’s well-known antioxidant properties, multiple clinical trials since the 1970s have found it ineffective as a cancer treatment. Thus, vitamin C has been largely ignored by conventional oncology and is usually offered only in alternative/complementary practices.
However, an article published in the Feb. 5 issue of Science Translational Medicine may reinvigorate research for this nutrient. The study found that vitamin C, when administered intravenously, induces cancer cell death without harming normal tissues. And in animal models, vitamin C made ovarian cancer cells more sensitive to the chemotherapy drugs carboplatin and paclitaxel.
Additionally, in an early-phase clinical trial involving 27 patients, those receiving vitamin C in addition to standard chemotherapy were less likely to experience toxic side effects. The finding suggests that vitamin C may have potential in helping patients tolerate higher and more powerful doses of chemotherapy.
“With enhanced understanding of [vitamin C’s] anticancer action presented here, plus a clear safety profile, biological and clinical plausibility have a firm foundation,” the study’s authors wrote, adding that these findings justify larger clinical trials to investigate vitamin C’s effectiveness in enhancing conventional chemotherapy for ovarian cancer.
Cancer will be defeated not in one enormous advance, experts agree, but in incremental advances. Those incremental advances often go unnoticed by the public at the time of their discovery, but in the years to come, they add up – to more life years, to greater survival rates, to more time spent with families and loved ones.
In 2014, patients will begin to see the benefits of many of those advances. Here, City of Hope’s physicians describe some of the recent scientific and medical developments they expect to benefit patients in the year ahead.
Breast cancer: A first-step therapy, now taken more seriously
Breast cancer remains a leading cancer killer of women (second only to lung cancer), but Joanne Mortimer, M.D., director of City of Hope’s Women’s Cancers Program, pointed to several studies that could begin to have a positive impact on treatment and survival.
The most significant recent development, she said, is the use of the monoclonal antibody pertuzumab as pretherapy (more formally known as neoadjuvant therapy) in HER2-positive breast cancer that has advanced locally. Such disease can be difficult to treat – and time is of the essence – so the Food and Drug Administration (FDA) earlier this year approved pertuzumab as neoadjuvant therapy when used along with the drugs Herceptin and docetaxel.
Such early treatment in high-risk patients is considered crucial to effectively fighting the disease.
“The results of this trial paved the way for using response to neoadjuvant chemotherapy as a surrogate for response and benefit to treatment of metastatic disease,” Mortimer said.
Other recent research suggests more effective therapies for women with metastatic disease. Mortimer pointed to a study that found neither mastectomy or lumpectomy and radiation were of benefit in treating the primary cancer, either initially or after response to systemic therapy.
“That suggests surgery may actually result in more rapid progression of metastatic disease,” she said. “In the absence of pain or local problems, mastectomy should not be performed outside of a clinical trial in this population.”
Cervical cancer: A notable drug advance and a simple, but powerful, test
Adding one drug to a treatment regimen can often have a significant difference; that appears to be the case with cervical cancer and the drug bevacizumab, which slows the growth of new blood vessels.
Robert J. Morgan M.D., co-director of the Gynecological Oncology/Peritoneal Malignancy Program at City of Hope, explained a recent study evaluating the role of the drug in addition to chemotherapy in metastatic carcinoma of the uterine cervix. “The addition of bevacizumab to chemotherapy resulted in a survival benefit from 13.3 months to an improved 17 months with very acceptable toxicity,” Morgan said.
“This is the first study that has resulted in a meaningful survival benefit for recurrent cervical cancer compared to the ‘standard’ chemotherapy of cisplatin and paclitaxel,” he added.
But cervical cancer must be detected before it can be treated and, for many parts of the world, that detection remains a significant hurdle. Recent findings could begin to change the outlook.
“In India, a study was carried out that used a simple method of identifying potential cervical cancers in areas that are too poor to have access to pap smear technology,” Morgan said. The method? The application of vinegar.
“Using trained observers and using acetic acid (vinegar) on the cervix, many early cervical cancers were identified,” Morgan said. “It is estimated that the mortality rate of this illness can be slashed by up to one third by this simple technique. “
He added: “It is still though important, particularly in this country, that women obtain regular gynecologic care and also that pre-teens and teenagers obtain the HPV vaccine.”
Endometrial (uterine) cancer: Understanding molecular changes
To fight a disease, doctors need to understand it.
“One problem with uterine and all gynecologic cancer is that we have not had a good understanding of how molecular changes in combination with histology may be beneficial in directing treatments,” said Morgan, also a professor and associate director for medical education in the Department of Medical Oncology & Therapeutics Research at City of Hope.
One recent study has improved that understanding considerably, giving researchers new avenues to explore. Morgan points to a large study using the Cancer Genome Atlas that analyzed molecular characteristics of 373 endometrial cancers, including low-grade endometrioid cancers, high-grade endometrioid cancers and papillary serous cancers. Researchers were able to identify four new categories of endometrial cancer based on the molecular characterizations of the tumors.
“This may well lead to treatment decisions based on molecular markers in addition to histological markers and allow better treatment with targeted agents,” Morgan said. “For example, one subset of high-grade endometrioid tumors had p53 mutations similar to papillary serous tumors, and the supposition is made that these may respond better to treatments designed for serous tumors.”
For women with endometrial cancer – and the doctors treating them – that kind of research-based guidance will be crucial to better outcomes.
Lung cancer: The benefit of precision therapies
In treating lung cancer, think “precision.”
Karen L. Reckamp, M.D. M.S., co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope, said physicians are increasingly using information on the genomics of lung tumors. With this information, they can better block cancer growth and improve outcomes by providing precision therapy for patients.
“In addition, we are beginning to understand the impact of activating the immune system to enhance the attack on tumor cells,” Reckamp said. “We may see a day when a patient’s own immune system can be directed against lung cancer.”
Meanwhile, Dan J. Raz, M.D., co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope, is emphasizing the importance of screening.
“Lung cancer screening is recommended by the U.S. Preventive Services Task Force,” he said. “Widespread adoption of lung cancer screening with low-dose radiation CT scanning has the potential to dramatically reduce death from lung cancer and turn lung cancer into a disease that is detected at an early stage a majority of the time.”
Ovarian cancer: Improved treatments on the way
The treatment of ovarian cancer is becoming both more effective and more complex.
“There are problems with the current standard treatments of ovarian cancer, including the fact that our treatments are similar despite differences in histology and grading of the tumors,” acknowledged Morgan. He cites a lack of research in smaller subsets of ovarian cancer and a lack of effective alternative therapies, despite the development of many targeted agents in the past decade.
But several developments suggest room for improvement in the coming year. For starters, a new drug, salumetinib, is showing promise against low-grade ovarian tumors that have been very difficult to treat. Further, Morgan added: “More agents directed at specific genomic mutations should result in improved treatments in the next few years.”
He also said that treatments could become easier on the patients themselves, pointing to new research on weekly schedules of the chemotherapy drugs carboplatin and taxol that suggests the regimen is just as effective, but less toxic than more traditional regimens.
Meanwhile, ongoing research into the PARP inhibitor olaparib suggests that it may improve treatment of hereditary ovarian cancers when used in the maintenance setting and that the angiogenesis inhibitor cediranib could improve survival in recurrent ovarian cancer.
More research is needed on these drugs before they can be used routinely, but the potential is promising.
Drugs aren’t the only option. “At City of Hope, we are collaborating in a T cell study investigating whether immune therapy may be beneficial in specific subsets of ovarian cancer patients,” Morgan said. “This is based on new knowledge of the immune system and how it plays a role in ovarian cancer.”
Pancreatic cancer: A novel approach to improve survivability
Pancreatic cancer’s lethal reputation comes from its stealth. As Gagandeep Singh, M.D., interim chair of the Department of Surgery at City of Hope, described the disease: “Fifty percent of pancreatic cancer is diagnosed at Stage IV, i.e., after it has spread, giving it a very bleak outlook.”
On the positive side, he noted, 50 percent of patients do not have metastatic disease. “While only 10 percent are operable at the time of diagnosis, the remaining 35 to 40 percent are considered locally advanced,” he said. “We strive to make these 40 percent operable, too, by a combination of neoadjuvant chemotherapy with radiotherapy followed by aggressive surgery or just aggressive surgery up front.”
Singh is optimistic about the future, especially as it relates to improvements in a procedure known as the Whipple, which involves the removal of the head of the pancreas along with the bile duct and the upper part of the intestine. During the surgery, tissue from the intestine is used to reconstruct the bile system, intestine and pancreas.
“We have been able to harness the advantage of the robot to do robotic-assisted Whipples by inserting hand-simulated instruments through tiny holes and then conducting the operation through these keyhole incisions,” Singh said. “The magnification, coupled with ease of use of these robotic instruments, adds to better and more radical clearance of the cancer.”
But choosing the right institution is crucial. “This is what is key – making sure those patients that have nonmetastatic pancreatic cancer go to the right institution at the right time to improve their survivability,” Singh said.
Prostate cancer: Using fluorescents to target disease
Timothy Wilson, M.D., the Pauline & Martin Collins Family Chair in Urology at City of Hope and director of the Prostate Cancer Program, has high hopes for doctors increasing ability to see precisely where cancerous cells stop and non-diseased cells begin. The key is fluorescence.
“The concept is the fluorescent label antibody against an antigen that sits on prostate cells, cancerous or not,” Wilson said. “You inject the fluorescent label antibody into the patient; it then targets and locates the prostate cell. And then during surgery, while doing it robotically, a switch is flipped that lights up that fluorescent label antibody so you see prostate tissue.”
He added: “This helps make sure we get all the cancer out or will help us see prostate cancer cells in lymph nodes.”
City of Hope plans to begin a clinical trial of that technique within months. It’s also exploring how to improve active surveillance, also known as “watchful waiting,” in men who have prostate cancer but who may not need immediate treatment. One method uses magnetic resonance imaging assessment of the prostate; another uses biomarkers.
Wilson referred specifically to the promise of a biomarker study by Steven Smith, Ph.D., professor of molecular science, urology and urologic oncology, that could help determine which men should stay on active surveillance and which men should receive treatment.
Radiation oncology: Getting a clear picture
For Jeffrey Wong, M.D., chair of City of Hope’s Department of Radiation Oncology, the future is looking not only brighter, but much clearer.
“There are two exciting trends for the field with the integration of imaging in radiation oncology,” he said. One involves what’s known as SBRT, for stereotactic body radiation therapy. This type of therapy uses very precise, very concentrated beams of radiation directed directly at the tumor. The other trend to watch uses ultrafocused sound with magnetic resonance imaging.
“For patients who refuse surgery or are medically unable to have surgery, SBRT can be used for lung patients with a 90 percent effectiveness in controlling the cancer,” Wong said.
As for magnetic resonance-guided focused ultrasound, or MRgFUS, it’s currently being evaluated by the Food and Drug Administration and is being tested to ablate prostate cancer, Wong said.
City of Hope’s Vicky Hoffman contributed to this report.