Posts tagged ‘pancreatic cancer’
The outlook and length of survival has not changed much in the past 25 years for patients suffering from an aggressive form of pancreatic cancer known as pancreatic ductal adenocarcinoma (PDAC). These patients still have few options for therapy; currently available therapies are generally toxic and do not increase survival by more than a few months.
Now, City of Hope researchers have identified a promising new strategy: a bacterial-based therapy that homes to tumors and provokes an extremely effective tumor-killing response.
In a study that appears in the journal Cancer Immunology Research, published by the American Association for Cancer Research, they report that the therapy frequently triggered the complete regression of pancreatic tumors and significantly extended survival in preclinical mouse studies. The study was led by Don J. Diamond, Ph.D., chair of the Department of Experimental Therapeutics at City of Hope, who believes that this method can be used to treat a variety of cancers that share similar features to PDAC.
Bacteria-based therapies have been used to treat solid tumors for decades and are commonly used to treat bladder cancer. Typically, an attenuated (i.e. weakened) form of the microbe is used as the therapy itself, or as a delivery vector to generate anti-tumor responses confined only to the cancer site. » Continue Reading
The news for pancreatic cancer is admittedly not good. Although overall cancer death rates continue to decline in the United States, pancreatic cancer is one of the few cancers with death rates projected to continue to rise in the next 15 years.
That’s why research is crucial. That’s why City of Hope is crucial.
By 2030, pancreatic cancer is expected to become the second-leading cause of cancer-related death in the United States, surpassing breast, prostate and colorectal cancers, according to a new study published this week in Cancer Research, a journal of the American Association for Cancer Research. Liver cancer will be the third-leading cause of cancer-related death, researchers predicted.
Lung cancer is currently the No. 1 cause of cancer-related death in the United States and will maintain that distinction, according to the report. (City of Hope’s Dan Raz, M.D., co-director of the Lung Cancer and Thoracic Oncology Program, has much to say on how to save lives from lung cancer, specifically through lung cancer screening.)
As for pancreatic cancer, Joseph Kim, M.D., City of Hope surgical oncologist and head of upper gastrointestinal surgery, says researchers and physicians are working to change the grim outlook for such diseases. » Continue Reading
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.
Treatment of pancreatic cancer starts with surgery, when operable. And though the overall statistics are often grim, newer treatment algorithms continue to evolve with the ultimate aim of beating this cancer.
Said Gagandeep Singh, M.D., chief of the Division of Surgical Oncology, and the head of pancreatic and liver surgery at City of Hope: “Pancreatic cancer is a top 10 cancer in the United States. It is the fourth-leading cause of cancer death in men and women. At City of Hope we have ongoing efforts to improve medical and surgical therapies – with added values of pancreatic cancer research to help find a cure and stop this disease.”
Singh discussed those ongoing efforts in a webinar on Wednesday, Aug. 28. He elaborated not only on the anatomy and physiology of the pancreas but also what makes pancreatic cancer surgery a formidable undertaking. He even explained how experts “stage” pancreatic cancer – that is, determine whether it’s Stage 1, 2, 3 or 4 – and how they devise treatment plans for the disease.
The main emphasis of his session, however, was the current leading-edge surgical procedures that City of Hope provides for pancreatic cancer patients, as well as the complexities that revolve around these operations.
The free event, sponsored by the Pancreatic Cancer Action Network, was meant for patients, caregivers and all level of health care workers. Singh discussed the various surgical procedures for this cancer, which include – but are not limited to – pancreatoduodenectomy (the Whipple Operation), total pancreatectomy, distal pancreatectomy (with and without splenectomy) and central pancreatectomy.
“The ultimate goal is to remove the cancer when possible,” Singh said before the webinar. “Surgery may not be appropriate for everyone, and chemotherapy with or without radiation therapy may be necessary to shrink locally advanced tumors to render them operable.”
For many Americans, the Fourth of July would not be the same without a backyard barbecue filled with steaks, hamburgers and hot dogs. But grill masters beware: research says high-heat grilling can increase cancer risk.
Cooking meats at very high temperatures converts proteins and sugars found in red meat, pork, poultry and fish into heterocyclic amines (HCAs), while dripping fats and juices from meat create polycyclic aromatic hydrocarbons (PAHs). Both compounds are known to cause DNA-altering changes that can increase the risk of cancer.
A study from the University of Minnesota found that eating charred, well-done meat on a regular basis may increase your risk of pancreatic cancer by up to 60 percent. And the American Institute for Cancer Research stated that consuming red and processed meats raises one’s risk of colorectal cancer.
“It is estimated that three-quarters of colorectal cancers, half of breast cancers and one-third of lung cancers could be prevented with healthier diets,” said Peggy Mancini, M.S., R.D., a clinical dietitian at City of Hope.
However, you don’t have to give up grilling completely to stay healthy. Here are a few tips on how you can lower your risk of cancer when hosting a summer barbecue: » Continue Reading
Imagine a familiar scenario straight out of your favorite scary movie.
A relentless villain sets his sights on a bunch of carefree teens. As the terror mounts, they throw one obstacle after another in his path. But lock a door and he breaks through a window. Barricade a window and he busts through the wall.
No matter what, he finds a way to keep … on … coming.
Cancer has a lot in common with our cinematic slasher. That’s how it gets ahead. It’s got a lot of different tools it uses to grow, multiply and spread. When one gets shut down, it often can find ways around the roadblock.
So doctors like Vincent Chung, M.D., are trying to stop cancer in several ways at once.
Chung, clinical associate professor of medical oncology, is leading a national trial testing a strategy that uses two innovative drugs together to fight pancreatic cancer. These trials usually match a targeted therapy with traditional chemotherapy, but Chung’s is different. Could it also be better?
One of the reasons pancreatic cancer is so tough to beat is that it can survive the damage caused by radiation and chemotherapy. But City of Hope researchers figured out a way to make pancreatic cancer cells more vulnerable to therapy. They hope to push their studies into clinical trials in the near future.
“Pancreatic cancer patients are a special case of the particularly unlucky, and in many ways the most miserable. The drug and radiation resistance of this cancer is legendary,” says City of Hope physician-researcher Sanjay Awasthi, M.D., who leads the effort.
So the scientists adopted a unique strategy: Put a cork in cancer cells’ exhaust system.
Awasthi, professor in the departments of Medical Oncology & Therapeutics Research and Diabetes, Endocrinology and Metabolism, and his team study RLIP76, a protein naturally found in the body. “It pumps out the toxic chemicals that accumulate in the cancer cell as a result of chemo- or radiotherapy, before they can cause cell death,” he explains.
They wondered if taking away the protein might keep the toxins in the cells long enough to kill the cells. So they tried it in the lab.
When they dropped levels of RLIP76 in pancreatic cancer cells and tumors in mice, and then exposed the cells to radiation or chemotherapy, the therapies killed cancer better. An added bonus: dropping RLIP76 also reduced blood sugar, cholesterol and triglyceride levels in lab mice. So medications that use this strategy to fight cancer might also battle diabetes.
They presented their results at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference in mid-June.
City of Hope radiologists are using the NanoKnife, a medical tool that destroys tissue using electricity, to zap stubborn tumors that do not respond to chemotherapy or radiation and that lie in locations that are difficult to reach with traditional surgery.
John Park, M.D., chief of the Division of Interventional Radiology in City of Hope’s Department of Diagnostic Radiology, and several of his colleagues have started using the new unit. The NanoKnife consists of several probes wired to an electric source. While a patient sleeps under anesthesia, doctors carefully insert the probes into the patient’s body so they surround the tumor. The physicians know just where to place the probes because they use CT scans, real-time ultrasound or other imaging methods to see the tumor’s location and size.
Once the probes rest in place around the tumor, the physicians send pulses of electricity into the NanoKnife. Electrons jump from probe to probe, jolting the tumor and punching holes in the cancerous cells in their path. The electricity flows for as little as 30 seconds. When it’s over, the tumor cells are damaged beyond repair. The body’s immune system then steps in to clean up dead cells.
The NanoKnife also affects nearby healthy tissues, but unlike surgery and procedures that use extreme heat or cold to kill tumor cells, the NanoKnife leaves the basic structures necessary for the body to rebuild the area with healthy cells. Best of all, patients report little or no pain following the procedure. “Patients want to go home as soon as they wake up,” Park said.
According to Park, the NanoKnife is most commonly used to treat tumors in soft tissues, such as in lung, prostate, pancreatic and liver cancers. Because clinical researchers are testing how well the NanoKnife works for specific cancers, the device currently is used only for patients with no other options or as part of a clinical trial.