Posts tagged ‘Timothy Wilson’


Urologic cancers: Dispatches from research’s front lines

March 28, 2014 | by

Urologic cancers, including prostate cancer, kidney cancer and bladder cancer, are diagnosed in more than 381,000 Americans each year, and almost 60,000 people die from the diseases. City of Hope’s physicians and scientists are determined to reduce those numbers.

Our groundbreaking research holds the promise of better treatments and cures for the millions of people worldwide battling these difficult cancers. The Division of Urology and Urologic Oncology, led by Timothy Wilson, M.D., Pauline & Martin Collins Family Chair in Urology and director of the Prostate Cancer Program, report the following developments in the treatment of urologic cancers.

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Overcoming drug resistance in metastatic prostate cancer

African American men are 60 percent more likely than white men to get prostate cancer and 2.4 times more likely to die of the disease.

The drug pyrvinium shows promise in the treatment of prostate cancer. Even better, it doesn’t target testosterone.

When prostate cancer metastasizes, it is signaled to grow by a protein called the androgen receptor, which is activated by testosterone. Many men initially respond to hormone treatments that inhibit testosterone, but prostate cancer cells adapt and develop resistance to these therapies, and the cancer almost always returns.

Jeremy Jones, Ph.D., assistant professor of Molecular Pharmacology, found that pyrvinium, a drug used for decades to treat pinworm infections, could treat metastatic prostate cancer without targeting testosterone. Pyrvinium works by inhibiting the DNA binding domain – a different part of the androgen receptor that’s activated when testosterone is blocked –  and could be effective when all other therapies have failed. Jones is testing pyrvinium derivatives in cell cultures and mice, and his goal is to reach phase I clinical trial in the next two years.

Jones is also working with Cy Stein, M.D., Ph.D., Arthur & Rosalie Kaplan Chair of Medical Oncology, to combine the action of two drugs, enzalutamide and abiraterone, to treat prostate cancer that is resistant to hormone therapy. They have designed a compound called COH11023 that inhibits the production of testosterone, prevents testosterone from binding to the androgen receptor and breaks down the androgen receptor to rid the cancer cells of the protein. » Continue Reading


Cancer treatment in 2014: Making the most of research

December 29, 2013 | by

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 tumor

Recent research is increasing doctors’ knowledge of, and ability to effectively treat, breast cancer. One significant development: the FDA approval of pertuzumab as neoadjuvant therapy.

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  

Illustration of the female reproductive system

Cervical cancer is not the threat it once was, thanks to Pap smears. But that doesn’t mean treatment can’t be improved. One significant development: The addition of the drug bevacizumab to some regimens.

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

Screening for lung cancer, shown here, can save lives, as studies have shown. Accordingly, lung cancer specialists are calling for increased screening.

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

ovaries

Cancer of the ovaries is difficult to treat, but not impossible. One significant development: Use of the drug salumetinib against low-grade ovarian tumors.

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

pancreas

Cancer of the pancreas can be difficult to treat. One significant development: improvements in the Whipple procedure.

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

prostate cancer

Prostate cancer treatment could become easier for physicians in some ways. One significant development: the ability to see the cancer via fluorescence.

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.

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 City of Hope’s Vicky Hoffman contributed to this report.

 

 


Prostate cancer abstract: So few words, so much impact

May 3, 2013 | by

The title was this: “Expressed Prostatic Secretions Biomarkers Improve Stratification of National Comprehensive Cancer Network Active Surveillance Candidates.”

Prostate cancer, illustrated here, doesn't always need immediate treatment. The dilemma is trying to decide when "active surveillance" is all that's necessary. A new abstract, from researchers at City of Hope, could help doctors and patients decide.

Prostate cancer, illustrated here, doesn’t always need immediate treatment. The dilemma is trying to decide when “active surveillance” is all that’s necessary. A new abstract, from researchers at City of Hope, could help doctors and patients decide.

And the conclusions were these: “Secondary screening by non-invasive EPS testing may improve patient acceptance of Active Surveillance by dramatically reducing the presence of occult risk factors in patients eligible for Active Surveillance under NCCN guidelines.”

  • In between were the details on the number of patients, their risk classifications when it came to the likelihood of the disease’s spread, how the secretions were obtained, various biomarkers and the like.

To those uninitiated in the world of research, this abstract on prostate cancer staging might have seemed standard fare. After all, it consisted of the usual introduction and objectives, methods, results and conclusions – and it was short. That’s the nature of abstracts. (Think of them as a movie trailer for the full-length film.)

But when all was said and done, not only had the researchers – from none other than City of Hope – produced a tidy synopsis of some impressive science, they’d also won the Best Abstract award from the American Urology Association. And they’ll be presenting their work at the association’s annual meeting in San Diego, held May 4 to 8.

“The award provides salience at the meeting and recognizes basic science research that will likely alter clinical practice by moving the presentation to the plenary session,” said Steven Smith, Ph.D.,   professor of molecular science in the Division of Urology and the principal investigator on the study. “This is a huge national meeting attended by thousands of practicing urologists and scientists.”

In short, City of Hope is helping shape the practice of urology. » Continue Reading


‘My cancer diagnosis: What I wish I’d known’ – Bill Brutocao

January 8, 2013 | by

One in a series of stories asking former patients to reflect upon their experience …

Soon after beginning treatment for prostate cancer at City of Hope in 2008, La Canada attorney Bill Brutocao received even more disturbing news. He was diagnosed with Hodgkin lymphoma.

Bill Brutocao, a former Hodgkin lymphoma patient

Former Hodgkin lymphoma patient Bill Brutocao, second from left, advises cancer patients not to become prima donnas. Cancer is hard on one’s family too, he says. He’s shown here with, from left, son Angelo, wife Christina, son Giancarlo and Giancarlo’s wife, Laura. (Photo courtesy Bill Brutocao)

Under the supervision of physicians Kevin Chan, M.D., clinical assistant professor of surgery in the Division of Urology and Urologic Oncology and Leslie Popplewell, M.D., clinical associate professor in the Department of Hematology & Hematopoietic Cell Transplantation, Brutocao suspended prostate cancer treatment and began enduring 12 rounds of chemotherapy to battle the lymphoma.

En route to treatment one day, Brutocao noticed signs for a creative writing class at the hospital. He was intrigued, but didn’t sign up. Though he thought the process might be therapeutic, he says, “the last thing I wanted to do was write about my illness.”

Yet, as he began to feel better, he reconsidered writing. He tackled a new genre – children’s literature – and wrote “The Basking Shark Rescue Team.”  Arguably, his fanciful characters – Beulah the Basking Shark, Sam the Seagull, Rocky the Otter and Corky the Cormorant – may have rescued their creator from the vortex of illness.

Brutocao, 62, is currently in remission from Hodgkin lymphoma but will require a prostatectomy in February that will be performed by Timothy Wilson, M.D., chief of the Division of Urology and Urologic Oncology at City of Hope and the Pauline and Martin Collins Family Chair in Urology.

Granddaughter Eleanora

Granddaughter Eleanora is just one of life’s pleasures for former Hodgkin lymphoma patient Bill Brutocao. (Photo courtesy of Bill Brutocao.)

Despite his medical challenges, Brutocao is optimistic about the future. Last August, he became a grandfather for the first time (to baby Eleanora). He might retire later this year but for now he’s working part-time as an attorney and also teaching intellectual property law at the University of La Verne Law School in Ontario. He has continued his saga of the Basking Shark gang (even inventing some new characters) in two more published books, “Rocky and the Great Bird Race”  and “Sancho at the Music Festival.”  And he has two more books in the works.

Compared to what he calls the “esoteric, arcane legal mumbo jumbo” he produces as an intellectual property lawyer, Brutocao finds his children’s books considerably more interesting to write – and read. “You’re only here for a little while,” Brutocao said. “You want to be remembered for something and I’d much rather be remembered as the guy who wrote ‘The Basking Shark Rescue Team.’”

We asked Brutocao to look back at the time of his diagnosis and to ask himself what he knows now that he wishes he’d known then. What wisdom, soothing words, practical tips or just old-fashioned advice would he give his newly diagnosed self? » Continue Reading


I, for one, welcome our new robot overlords … uh, surgeons

August 21, 2012 | by

For such a small gland, the prostate stirs up a lot of debate. It seems that every month brings a new study that raises questions about how best to detect, diagnose and treat prostate cancer. And it’s that time again.

Photo of minimally invasive robotic surgery

Clayton Lau, right, during a minimally invasive robotic surgery. (Photo by Alicia Di Rado)

This time it’s about the best way to operate.

When a prostate cancer patient chooses to have his cancer removed through an operation, he has a few options: a traditional open surgery, where the surgeon makes an incision across the patient’s entire lower abdomen; and laparoscopic surgery, in which surgeons operate using long, thin instruments inserted through small punctures or slits in the skin.

Robotic-assisted surgery takes laparoscopic surgery a step further. The surgical instruments are mounted on a robot, which surgeons control from a console.

Surgeons have performed robotic surgery for prostate cancer for a decade, but published studies still debate whether robotic surgery is any better than open surgery. City of Hope’s Timothy Wilson, M.D., Pauline and Martin Collins Family Chair in Urology, helped organize an international panel of surgeons to review data to see if they could come up with some answers.

So what did all these surgeons find?

» Continue Reading


How do you take the measure of a man?

May 17, 2012 | by

Warren Buffett’s recent revelation about his prostate cancer diagnosis re-opened the debate over age and prostate cancer screening and treatment. At 81, Buffett falls outside of the commonly used guidelines that men over 75 don’t need to be screened for prostate cancer.

The United States Preventive Services Task Force made this recommendation in 2008, noting that most men over age 75 who develop prostate cancer die from other causes. Since prostate cancer in older men tends to develop slowly, experts say, these men do not need treatment that can cause incontinence and other side effects.

Interestingly, the task force announced its prostate cancer screening recommendations a year before it unveiled its recommendation that breast cancer screening should begin at 50 instead of the current 40 years of age. There was sustained public outrage over the breast cancer screening recommendations, but little hubbub over the guidelines on prostate cancer.

We should remember that guidelines are created to help the majority of people, and individuals can fall on either side of that bell curve — developing prostate cancer earlier or later in life than the typical patient. Men are encouraged to talk with their doctor about their personal health concerns and whether screening is right for them.

Timothy Wilson, M.D., Pauline and Martin Collins Family Chair in Urology and chief of the Division of Urology & Urologic Oncology, shares his thoughts in this video about the value of prostate cancer screening.


Why should men care about prostate cancer?

October 10, 2011 | by

Timothy Wilson, M.D., Director, Prostate Cancer Program and Chief of the Division of Urology and Urologic Oncology Cancers at City of Hope, discusses why men should pay attention to prostate cancer, why screening is important, and outlines the many options and dispels fears about treatment side effects.