Viagra drug trio improves effectiveness of cancer treatment while protecting the heart

A new drug combination featuring the widely-known impotence drug Viagra has been found to improve the effectiveness of cancer treatment while protecting the heart from harm caused by a popular form of chemotherapy. With nearly half of all cancer survivors dying from other conditions than cancer, most notably cardiovascular disease, this new treatment is not only innovative but necessary.

Recently presented at the American Heart Association’s Scientific Sessions in Los Angeles, the study was co-authored by Rakesh Kukreja, M.S., Ph.D., researcher in the Developmental Therapeutics program at VCU Massey Cancer Center and scientific director at VCU Pauley Heart Center. 

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The research team used breast cancer cells and cardiomyocytes (heart cells) to study the effects of combining three drugs. The three drugs included cancer-fighting chemotherapy doxorubicin (Doxil, Andriamycin), erectile dysfunction medication Viagra (sildenafil) and immunosuppressant antibiotic rapamycin (sirolimus, Rapamune).

For decades, doxorubicin has been a powerful and effective drug for patients with various types of cancer, such as breast, ovarian, colon and prostate. Unfortunately, the drug can cause harmful and irreversible side effects to the heart.

Over the past 15 years, researchers have been working to find an optimal therapeutic intervention for protecting the heart against damage caused by doxorubicin.

“Currently, dexrazoxane is the only FDA-approved drug that can prevent heart damage caused by doxorubicin. But, this drug can decrease patients’ bone marrow activity, resulting in fewer red blood cells, white blood cells and platelets, and interfere with the anti-cancer efficacy of doxorubicin,” explains Kukreja.

In earlier studies, Kukreja and his colleagues found that administering Viagra before doxorubicin prevented heart damage in mice while triggering cell death in prostate cancer cells. He and his research team were also the first to demonstrate in preclinical animal models that rapamycin protects the heart against tissue damage following acute heart attack.

With that in mind, the researchers developed a new ‘drug trifecta’ that has been found to not only improve the anti-cancer effects of doxorubicin, but to also reduce damage to the heart caused by doxorubicin.

“Because Viagra and rapamycin are clinically approved drugs that both protect heart muscle, we thought that combining these with doxorubicin would be a promising strategy to eliminate the cardiac side effects of the drug while further improving its cancer-killing ability. Such a unique combination has never been used before,” said Kukreja.

What they found was that the drug combination led to a dramatic protection of heart cells from apoptosis (naturally occurring programmed cell suicide) and necrosis (cell death caused by infection, toxins or trauma) while significantly improving the anti-cancer effects of doxorubicin .

Researchers say the next step in the study will be to demonstrate how the drug trio improves cancer treatment in animal models with human cancers. Also, more research is needed to understand how Viagra and rapamycin work together to improve doxorubicin treatment.

“Since all of these drugs are clinically approved, we are hopeful that this unique combination therapy may have excellent potential for future clinical trials in cancer patients,” Kukreja says.

The full abstract of this study can be found online at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6ba1f3a6-681f-44c5-b6f4-6f4554516b27&cKey=9b5ef827-43cd-4505-a0f3-3faee48f349f&mKey=%7B14145D5B-F96B-4354-8237-8F0937744BA4%7D

Collaborators on this study were David Durrant, Ph.D. candidate at the VCU School of Medicine, Anindita Das, Ph.D., assistant professor at the VCU School of Medicine and researcher at VCU Massey Cancer Center, and Fadi N. Salloum, Ph.D., assistant professor at the VCU Pauley Heart Center.

This research was supported, in part, with funding from the National Institutes of Health grants HL51045, HL79424 and HL93685. 

New Research on Employment-Based Insurance Sheds Light on Health Care Reform

Men with employment-contingent health insurance (ECHI) who suffer a health shock, such as a cancer diagnosis or hospitalization, are more likely to feel “locked” into remaining at work and are at greater risk for losing their insurance during this critical time as compared to men who are on their spouse’s insurance plan or on private insurance plans, according to a new study by Virginia Commonwealth University Massey Cancer Center.

Thumbnail image for Thumbnail image for Cathy Bradley, PhD.jpgPublished in the International Journal of Health Care and Economics, the study was led by Cathy J. Bradley, M.P.A, Ph.D., RGC  Professor for Cancer Research and co-leader of the Cancer Prevention and Control program at VCU Massey Cancer Center and chair of the Department of Healthcare Policy and Research at VCU School of Medicine. The researchers used the Heath and Retirement Study surveys (conducted every two years by the University of Michigan of more than 26,000 Americans over the age of 50) from 1996 through 2008 to observe employment and health insurance status among 1,582 men. They focused on the individuals who participated in the interviews two years apart and whether a health shock occurred in the intervening period between the interviews. The results shed light on potential benefits and drawbacks of the Affordable Care Act (ACA).

“With the passage of health care reform, the tendency of those with employment-contingent health insurance, as opposed to other sources of insurance, to remain employed following a health shock such as cancer, may be diminished slightly, along with the likelihood of losing health insurance,” said Bradley. “The Affordable Care Act (ACA) will provide an option to purchase affordable private insurance and eliminate pre-existing condition clauses, which would be helpful to someone who could no longer work.”

Bradley’s team distinguished between different kinds of health shock – health shocks that contribute to a decline in overall health and financial shocks, or those which contribute to higher future health care costs but not a decline in overall health. In addition, the researchers separated respondents into different groups to compare the effects of the health shocks on men with ECHI and on men with another type of health insurance. “Our findings suggest that financial shocks are more likely to contribute to employment lock because adequate health insurance would be too costly under private plans,” explains Bradley. “Additionally, we found that men with access to their spouse’s plans were less likely to remain employed following a health shock. However, we found most respondents did not consider their wives’ policy as a viable option for health insurance.”

Although the results paint a bleak picture for men solely dependent on their employers for insurance, this research comes at an influential time as new health care reform takes effect.

Bradley plans to continue exploring the relationship between health insurance and employment, treatment decisions and recovery from treatment. She recently collected data from 625 women with breast cancer and is working toward publishing several additional studies on these topics.

Collaborators on this study were David Neumark, Ph.D., professor of economics, director of graduate studies, director for The Center of Economics and Public Policy at the University of California, Irvine, and Meryl Motika, doctoral student at the University of California, Irvine.

The full manuscript of this study can be found online at: http://www.springerlink.com/content/725w335271375754/fulltext.pdf.

This research was supported, in part, with funding from NCI grant RO1-CA122145 and VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059.

Physician-researcher receives 2012 Alliance Research Grant

VCU Massey Cancer Center hematologist-oncologist Beata Holkova, M.D., was recently awarded an Alliance Research Grant to support her work involving drug combinations to battle B-cell lymphomas. The grant was presented at this year’s Alliance Group Meeting in Chicago, Illinois. Holkova is a Harrison Endowed Scholar and member of the Developmental Therapeutics research program at VCU Massey Cancer Center and assistant professor of hematology-oncology and internal medicine at the VCU School of Medicine.

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Each year, The Alliance for Clinical Trials in Oncology Foundation awards grants to junior oncology faculty to support their research activities. Research can include studies that assess interventions in cancer patients and/or research that examines biological specimens obtained by cancer patients. 

In Holkova’s case, her phase I clinical trial combines carfilzomib, a proteasome inhibitor, with obatoclax, a Bcl-2 Inhibitor, an experimental combination, in relapsed/refractory 

B-cell lymphomas in hopes of finding a drug combination that will help patients who suffer from forms of lymphoma that are resistant to conventional therapies.

Translational research: from bench to bedside

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Maria Quigley, R.N., and Andrew Poklepovic, M.D., are conducting 
clinical trial studying a combination of chemotherapies 
f
or the treatment of advanced malignancies. 

 

Since 1974, VCU Massey Cancer Center has been at the forefront of groundbreaking research to help save and improve the lives of those affected by cancer.  Bringing the latest discoveries to patients is the core of Massey’s mission. 

Massey’s science-driven translational research – moving scientific discoveries from the laboratory into real-world patient applications – is one of the many reasons the National Cancer Institute (NCI) recently awarded Massey a five-year renewal as one of only two NCI-designated Cancer Centers in Virginia. 

Often described as “bench-to-bedside” research, translational research involves several stages, including clinical trials, where consenting patients are given drugs, surgical procedures, devices or other interventions to treat cancer and are then closely monitored to determine side effects, effectiveness and other key findings. 

The four phases of clinical trials help provide scientists and clinicians with a variety of important information and data, from a drug’s dosage toxicity, for example, to side effects and patient benefits as well as risks. 

During Phase I trials, drugs are tested for the first time in small groups of participants in order to evaluate safety, to determine dose ranges and to identify side effects. 

Two of Massey’s Phase I trials have yielded promising results in the treatment of acute forms of leukemia and in cases of advanced malignancy such as breast cancer. 

Steven Grant, M.D., Olsson Chair in Oncology Research, associate director for translational research and co-leader of Massey’s Developmental Therapeutics program, is leading a research team studying the use of two targeted agents, belinostat (a histone deacetylase inhibitor, which acts by modifying the expression of genes involved in the regulation of cell differentiation and death) and bortezomib (a proteasome inhibitor that interferes with the cell’s ability to degrade unwanted proteins), for the treatment of acute leukemia. 

Funded in part by a highly competitive NCI $1.2 million “Grand Opportunities” award, the trial is a collaborative effort with M.D. Anderson Cancer Center in Houston, Texas, and H. Lee Moffitt Cancer Center in Tampa, Florida.  The preclinical findings from Grant’s lab studies at Massey showed that very low concentrations of the two agents used in combination were toxic to leukemia cells found in patients. Now in the Phase I clinical trial stage with principal investigator Beata Holkova, M.D., the research is designed to determine how participants tolerate various dose levels of the combination. Although still preliminary, results to date have been encouraging. 

“We’ve been able to translate our basic laboratory findings into the clinical arena and have had three patients who have either achieved or who have come close to achieving a complete remission,” Grant said. “That is not to say that the leukemia has been cured, only that at a certain point the leukemia was not detectable by standard means following treatment.” 

Such responses open up additional therapeutic options for leukemia patients, and point  the way toward promising outcomes. 

“Massey’s support of this research demonstrates the commitment of the institution to move laboratory findings forward to yield tangible benefits to patients,” Grant said. “It is an essential component of our success.”

Another example of Massey’s promising translational research involves the study of a different powerful drug combination. Principal investigator, Andrew Poklepovic, M.D., is leading the effort to study the use of pemetrexed (a multitargeted antifolate that prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells) and sorafenib (a multikinase inhibitor which works by slowing the spread of cancer cells) to treat advanced malignancies.

Originally co-developed by Massey scientist Rick Moran, Ph.D., Massey’s associate director for basic research, pemetrexed is now a leading medication for use in lung cancer treatment. Collaboration between Moran and Paul Dent, Ph.D., Universal Corporation Distinguished Professor in Cancer Cell Signaling, led to the discovery of additional anti-cancer applications for pemetrexed and even more anti-cancer benefits when the drug is used in combination with sorafenib. This combination explores a new strategy in fighting cancer known as toxic autophagy. 

“We’ve had a very good response in triple negative breast cancer, a disease that’s very difficult to treat and an area of real need,” Poklepovic said. Colon cancer, he added, may also be responding to the drug combination. “We frequently find that drugs working through one pathway or mechanism also work in other mechanisms. Pemetrexed’s alternate mechanism was found during Moran and Dent’s collaboration at Massey.” 

Because of the early and positive responses to breast cancer, the trial, which is funded entirely by Massey grants and philanthropic donations, has attracted additional support from the pharmaceutical industry in the form of drug contributions to the study. Such contributions can represent hundreds of thousands of dollars of a researcher’s budget.  “It wouldn’t have been possible to attract this additional support without the generosity of Massey and private donors,” he said. 

According to Poklepovic, many cancer centers have ideas that aren’t progressing to the trial level because of the lack of outside funding. When Massey sees a good idea, he said, external funding helps support the research. “And there are a lot of good ideas coming out of Massey.” 

Funding isn’t the only critical piece necessary for successful translational research.  At the center of all Massey research is the patient. Clinical trials wouldn’t be possible without volunteer participants who are willing to trust not only the scientific process, but also the team at the helm of such significant advancements in laboratory research and in clinical practice. 

“When we talk to patients, we explain that there are no guarantees,” said Mary Beth Tombes, R.N., clinical research nurse on Grant’s leukemia trial team. “We explain that we’ve had some good responses, but it still requires a leap of faith on the patient’s part.” 

That leap of faith resulted in remission for several participants in these two trials alone, and investigators are optimistic that there are more success stories to come. At Massey, more than 100 trials involving more than 20 types of cancer provide vital information for the continued development of new treatments. 

Many clinical trial participants make the decision to volunteer because of the opportunity to help themselves and to help others. Each works with and is monitored by a team of dedicated health care specialists including physicians, researchers, social workers, administrators and nurses, like Tombes. 

“It’s a real honor to care for people who are willing to participate in such an important process,” she said. “We go out of our way to make things easier for them. They are making a huge commitment to enhancing the body of medical knowledge and it’s an honor to be a part of that.” 

“This is how new discoveries are made,” said Poklepovic. “The hope for tomorrow lies in the things that are being developed now.”

Why women physicians choose academic medicine

Today, as many women as men attend medical school where academic medicine is a career option equally available to all. Yet, of the approximately 125,000 medical school faculty members in the U.S., only 35 percent are women, and until recently, no one knew why. 

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This question intrigued Amelia Grover, M.D., assistant professor in the division of surgical oncology at the VCU School of Medicine and a researcher at VCU Massey Cancer Center. She joined a small team to study how, why and when physicians choose to practice academic medicine. After an extensive literature review in which they found that gender differences play a role in the decision, the team continued on to discover the factors that influence women physicians specifically to choose academia.

The result of this investigation is the article “Women Physicians: Choosing a Career in Academic Medicine”, published in Academic Medicine by Dr. Grover and co-investigators Nicole J. Borges, Ph.D., Wright State University Boonshoft School of Medicine, and Anita M. Navarro, M.Ed., Association of American Medical Colleges. 

After interviewing 53 women physicians who had chosen careers in academic medicine, the researchers identified five main themes related to why the interviewees had made the choices they did. The broad factors are:

  • Fit, defined as a sense of congruence between their lives and their careers.
  • Aspects of the academic health center (AHC) environment, including intellectual stimulation, teaching, variety, training opportunities and lifestyle.
  • The influence of people in their lives, including mentors and parents.
  • Exposure to academic medicine.
  • Interest in practicing clinical medicine.

“The environment in which one trains seems to be a substantial influence” on the decision, the researchers found. For example, those who trained in a teaching hospital were exposed to more of the factors and were more likely to have role models and mentors with a background in academic medicine.

Even so, women physicians do not choose academic medicine early in their career path. After identifying the stages relating to when the decision was made, the researchers found that, in all but three instances, study participants chose academia during residency, as a fellow or as a practicing physician. “Participants indicated overwhelmingly that as medical students they did not know enough about academic medicine to choose it as a career.”

How the participants chose academic medicine was the third avenue studied. Career changes prompted some participants, whether due to changing interests or dissatisfaction with their former career. Other themes affecting the decision were “emotionality” (love of teaching, for example), “parental influence” and their “decision-making style.” 

The career decisions made by some interviewees came after chance encounters with one or more influencers who suggested, or exposed them to, academic medicine. The serendipitous nature of these decisions “may indicate that physician educators miss opportunities to cultivate the talents of trainees who have not necessarily been identified as having interests in academic medicine but who, nonetheless, may be – or could become – interested,” the researchers write.

These insights suggest steps medical schools and residency programs can take to introduce careers in academic medicine to their trainees. Providing students with opportunities earlier in their training to determine whether the AHC environment is an appropriate fit, for example, can make a difference.  

The team’s findings are as important as they are timely. Knowing as much as possible about why physicians choose academic medicine is vital if the medical education community is to going to address the looming physician shortage effectively.

In addition, bringing more women into academic medicine will increase diversity and create more role models. “Each individual brings unique ideas and ways to address questions and problems,” Grover reasons. “These are formed by their gender, ethnicity, generation, life experiences, etc. This diversity better enables us to understand and help our patients, ask and answer research questions and teach the future generations of health care workers. It is like Aesop’s fable of the elephant,” she concludes. 

Women in Science, Dentistry and Medicine

In addition to increasing the recruitment of women, the academic medicine community needs to provide the support required for women to succeed in their field of practice. VCU embraces this tenet. One of many examples of this commitment is Women in Science, Dentistry and Medicine (WISDM).

Established in 1992, WISDM seeks to further the professional goals and career development of women physicians, scientists and dentists at the VCU Schools of Medicine and Dentistry. “Our objective is to help open communication channels that facilitate networking, mentoring and collaboration among faculty members,” says Amelia Grover, M.D., this year’s president. “In this way, we can promote scientific and teaching excellence in women faculty, which in turn will increase the participation and leadership of women within the organizational structure of the medical and dental schools.

WISDM sponsors an annual leadership conference that has been recognized by national executive leadership associations for its excellence. The 2012 conference celebrated WISDM’s 20th year with the theme “Making a Difference: the Meaning of Service.” Ann Maust, CEO of New Visions, New Ventures was the keynote speaker. Massey’s Community Advisory Board member Becky Massey served as a panelist discussing the work and rewards of volunteerism.

Massey rated the top cancer center in Virginia by U.S. News

US_News_Best_Hospitals_Cancer.jpgAs reported in the July issue, U.S. News & World Report rated Virginia Commonwealth University Massey Cancer Center the top hospital in Virginia providing high-performing cancer care in the publication’s annual Best Hospitals list.

Ranked the No.1 hospital overall at the top of all 127 Virginia and 21 Richmond metropolitan hospitals is VCU Medical Center, which includes Massey’s oncology patient care.

VCU Medical Center is the only hospital in the state with four nationally-ranked specialties in the top 50 – nephrology, pulmonology, orthopaedic surgery and urology – and nine other high-performing specialties, including cancer care at Massey.

“VCU Massey Cancer Center is pleased to be recognized for its state-of-the-art, compassionate cancer care,” said Gordon D. Ginder, M.D., director of VCU Massey Cancer Center. “We are committed to discovering new and better cancer treatments that save and improve the lives of individuals with cancer.”

This year’s Best Hospitals ranking showcases more than 720 of the nation’s roughly 5,000 hospitals. Fewer than 150 are nationally ranked in at least one of 16 medical specialties. The rankings are based upon many factors, including reputation, patient survival, patient safety and care-related factors such as nursing and patient services.

The hospital rankings are like a GPS-type aid to help steer patients to hospitals with strong skills in the procedures and medical conditions that present the biggest challenges, said U.S. News Health Rankings Editor Avery Comarow. “All of these hospitals are the kinds of medical centers that should be on your list when you need the best care. They are where other hospitals send the toughest cases,” said Comarow.

Sheldon M. Retchin, M.D., M.S.P.H.,CEO of the VCU Health System and vice president for VCU Health Sciences, said the No. 1 ranking in the Commonwealth “is a fantastic endorsement of our commitment to excellence in patient care.” He added that it also reflects “our goal of bringing the latest and best therapies, treatments and cures to our patients and to the community.”

The VCU Medical Center ranked as high-performing in:
•    Cancer
•    Cardiology & Heart Surgery
•    Diabetes & Endocrinology
•    Ear, Nose & Throat
•    Gastroenterology
•    Geriatrics
•    Gynecology
•    Neurology & Neurosurgery
•    Rehabilitation

The complete rankings are available online at http://health.usnews.com/best-hospitals.

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Committed to a cancer-free Virginia

Long known as an exceptional cancer resource for the Richmond region, Massey is also dedicated to extending the most advanced cancer treatments and innovative research throughout Virginia. Recent increases in support from the state General Assembly, along with funding from the Tobacco Indemnification and Community Revitalization Commission (TICRC), have helped broaden Massey’s reach far beyond Richmond to almost every corner of the Commonwealth. These statewide initiatives are providing resources for health education, assessing community cancer needs and increasing opportunities for those facing cancer to participate in clinical trials and cancer prevention and control research. (Click map to enlarge it.)

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Empowering rural communities

The Cancer Resource Center of Southern Virginia in Danville facilitates the availability of local, state and national cancer assistance programs for individuals living within the southern regions of the Commonwealth. The Center identifies specific services of value to residents affected by cancer through the guidance of a Cancer Task Force composed of local cancer care providers, community organizations and health district leaders, all in partnership with Massey. The Center connects individuals to resources like transportation to medical appointments, organizations providing co-payment assistance and providers for the uninsured.

Providing health information at Virginians’ fingertips

Massey’s Health Information & Advocacy @ Your Library program makes reliable and accurate information about cancer and other health topics readily available through an online portal and at ten Southside Virginia county library systems.

Engaging underserved communities

In underserved communities like Petersburg that have extremely high cancer incidence and mortality rates, Massey researchers are conducting town hall meetings to develop long-term, evidence-based programs to address community needs.

Increasing access to innovative research and clinical trials

Massey is expanding its cutting-edge cancer therapies and groundbreaking research to more Virginians through its network of affiliations with community hospitals and oncology practices. These satellite facilities and partnerships give more residents greater access to clinical trials, genetic counseling, telemedicine and cancer prevention and control research, which is related to behavioral, policy, organizational and environmental factors that affect cancer risk, diagnosis, treatment, survival and quality of life.

Egidio Del Fabbro named program director of palliative care at Massey

Del Fabbro, Egidio headshot-suit-blog150.jpgEgidio Del Fabbro, M.D., has been named program director of palliative care at Virginia Commonwealth University Massey Cancer Center, effective May 1, 2012.

A nationally recognized expert in palliative care – comprehensive care for patients and families with a focus on alleviating suffering from serious illness – Del Fabbro comes to VCU Massey from The University of Texas MD Anderson Cancer Center in Houston, where he is currently an associate professor in the Department of Palliative Care and Rehabilitation Medicine. He is also director of the Outpatient Cachexia Clinic and associate director of the Palliative Care Fellowship Training Program.

Del Fabbro, who will also serve as an associate professor of internal medicine within the Division of Hematology, Oncology and Palliative Care of the Department of Internal Medicine at the VCU School of Medicine, is a physician and scientist with specific clinical and research interests in cancer-related fatigue and cachexia (involuntary loss of weight caused by disease). He directs a robust research program with a history of peer-reviewed funding, and he is a member of the American Academy of Hospice and Palliative Medicine (AAHPM) Research Committee.

At VCU, Del Fabbro will work closely with Steven R. Grossman, M.D., Ph.D., chair of the Division of Hematology, Oncology and Palliative Care, and Gordon D. Ginder, M.D., director of VCU Massey Cancer Center, to focus on the continued growth of the palliative care program, specifically on increasing its outpatient presence and integration of palliative care across all oncology services, as well as further enhancing its national and international reputation.

“We are delighted to have Dr. Del Fabbro join us to lead our Thomas Palliative Care Program. His addition is integral to the Program’s long-term growth and continued success as one of the world’s foremost leaders of palliative care treatment, research and training,” said Grossman.

“Dr. Del Fabbro brings valuable knowledge and experience to an important leadership role at VCU Massey Cancer Center,” Ginder said. “He will significantly contribute to the Center’s excellence in cancer care, research and education.”

Del Fabbro received his medical degree from the University of the Witwatersrand in Johannesburg, South Africa. He completed his residency in internal medicine at Barnes-Jewish Hospital in St. Louis and his fellowship in palliative care at MD Anderson.

Clinical trial shows benefit to adding Avastin to neoadjuvant chemotherapy in breast cancer patients

Amid the controversy surrounding the Food and Drug Administration’s ruling that Avastin should no longer be used to treat metastatic breast cancer, a new multinational Phase III clinical trial shows that Avastin significantly increased tumor response rates in breast cancer patients when given before surgery.

BEAR_H_160x240_092211.jpgAt the annual meeting for the American Society of Clinical Oncology, the nation’s premier association of clinical oncologists, Harry D. Bear, M.D., Ph.D., Chair, Division of Surgical Oncology at Virginia Commonwealth University Massey Cancer Center, presented the Avastin findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-40 clinical trial. Bear, who served as the trial’s protocol chair, explained that Avastin, when added to preoperative chemotherapy regimens, increased toxicity but also increased pathologic complete response rates by more than 6 percent (34.5 percent versus 28.4 percent) and clinical complete response rates by approximately 8 percent (64.3 percent versus 55.8 percent). “Pathologic complete response” was defined in the study as no remaining invasive cancer left in the breast, and “clinical complete response” was defined as a complete disappearance of cancer with no evidence of disease progression. Patients with hormone receptor positive breast cancers appeared to benefit most from the treatment.

“While encouraging, the results of this study will probably not affect standard neoadjuvant or adjuvant chemotherapy practices in the near term,” says Bear. “There are many different types of breast cancer, and we need more definitive biological predictors of response in order to more accurately identify the patients who will benefit most from Avastin.”

Though hormone receptor positive patients benefited most from the addition of Avastin in the NSABP Protocol B-40 trial, a second study presented during the same session at the ASCO meeting seemed to contradict the findings. The second study, known as GeparQuinto, was conducted in Germany and found that Avastin benefitted patients with triple negative cancers, but not patients with hormone receptor positive cancers.

“The more we understand tumor biology, the more personalized cancer care becomes. By identifying the factors that made Avastin beneficial, we can hopefully test future breast cancer patients to determine whether or not it should be included in their treatment,” says Bear.

The NSABP Protocol B-40 trial included 1,206 patients with operable HER2-negative breast cancer and tested different preoperative, or “neoadjuvant,” chemotherapy regimens. The trial had two objectives. The first was to determine whether adding the chemotherapy agents capecitabine or gemcitabine to the standard neoadjuvant chemotherapy regimen of docetaxel followed by a combination of doxorubicin and cyclophosphamide increased the pathologic complete response rate. The second objective was to test whether adding Avastin to chemotherapy before surgery increased the pathologic complete response rate. While the addition of Avastin did improve the pathologic complete response rate, the addition of the chemotherapy agents capecitabine and gemcitabine did not.

“We need more research focusing on patient biology and tumor differences to understand why Avastin works for some but not others. We hope to gain insight by analyzing tumor biopsies and blood samples from patients in the B-40 trial and other recent Avastin studies,” says Bear. “In addition, since the patients who received Avastin preoperatively also received it after surgery, it is possible the drug may improve long-term outcomes. We will follow these patients for many years to come to determine whether Avastin increased cure rates.”

Researcher awarded NCI grant to investigate novel anti-tumor vaccine

WANG_XIANG-YANG_160x240_092211.jpgXiang-Yang (Shawn) Wang, Ph.D., was recently awarded a $310,213 grant from the National Cancer Institute to support his research involving large stress proteins (LSPs) in immune regulation and cancer immunotherapy. Wang is a VCU Massey Cancer Center Harrison Scholar, member of the VCU Institute of Molecular Medicine and associate professor of human and molecular genetics at the VCU School of Medicine.

The NCI grant will fund Wang and his team as they investigate the immunologic effects and therapeutic potential of LSPs. Specifically, they will work to determine the mechanisms that allow or prevent LSPs from presenting tumor antigens, to understand how LSPs modify immune responses by interacting with molecules associated with specific pathogens and also to evaluate the therapeutic activity of an improved vaccine utilizing LSPs loaded with tumor antigens, also known as a chaperone vaccine.

LSPs act as molecular chaperones for other proteins, assisting with a process known as protein folding as well as transportation across membranes within a cell. LSPs are produced as a response to cellular stressors ranging from heat and inflammation to invading pathogens. They are thought to be a link between the body’s innate and adaptive immune systems by first responding to the initial stress and then presenting certain antigens, or molecules, on their surface for immune cells to target. Prior research from Wang’s laboratory found that LSPs carrying a melanoma protein antigen demonstrated a highly potent anti-tumor immune response in animal models.

Cancer immunotherapy is a fairly young field. Using the body’s own protective mechanism is attractive for several reasons, including low toxicity, a high degree of specificity and a long-lasting immunity.

Wang’s research will shed light on the biological and immunological mechanisms at play in chaperone vaccines, and facilitate the development of novel immunotherapies for the treatment of cancer and other diseases.