Q&A With Dr. Scott Hiebert at Vanderbilt-Ingram Cancer Center

hiebert_scott_croppedThank you for attending our recent scientific research meeting. What was your top takeaway? One of the things that struck me was the success of using three drugs to combat HIV and how successful this approach has been. We use combination therapy in cancer, but rarely can we apply three drugs at once due to toxicity. This has to be our goal as using multiple drugs at once makes resistance less likely to occur.

Please tell us a little about your research funded by the T.J. Martell Foundation. The work funded at Vanderbilt spans most of the critical cancer types from breast cancer to lung cancer to leukemia. This work is aimed at not only making new drugs, but using the drugs we have in a smarter way.

Why and how did you begin doing this type of work? I got hooked in graduate school. I had a mentor in college who suggested graduate school and once I started discovering new information never before uncovered, I was hooked. We do “hypothesis” based research where we test our best guesses, so its a little like gambling and its easy to get hooked.

Why is the T.J. Martell Foundation’s continued support so important to your research? The support of the T. J. Martell Foundation supports every aspect of our work in that it allows us to try risky new experiments and develop new veins of discovery that would not be funded by the NIH.

What are some of the most important things people can do to decrease their cancer risk? Don’t smoke, eat a healthy diet, exercise, and screen, screen, screen—colonoscopy when you are 50, prostate and breast exams, and make sure that your kids and grandchildren get the HPV vaccine. This vaccine will prevent cervical cancer and half of head and neck cancers in men and women.

Dr. Scott Hiebert is Associate Director for Basic Science Research and Shared Resources, Hortense B. Ingram Professor of Cancer Research, Professor of Biochemistry, Associate Professor of Medicine, and Researcher at Vanderbilt-Ingram Cancer Center in Nashville.

Cancer and Collaboration

Levy_MiaOne of the bedrocks of our organization is encouraging collaboration between scientists and institutions. We feel strongly that we will find a cure faster when great minds work together. That is why we are so excited about this news from our partners at Vanderbilt-Ingram Cancer Center, who have joined an international consortium of leading cancer centers to share genomic data from patients in an effort to accelerate the pace of cancer research and improve precision medicine.

The American Association for Cancer Research (AACR) launched the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) to facilitate data sharing among major cancer centers and researchers.

VICC’s participation in AACR Project GENIE has been spearheaded by Mia Levy, M.D., Ph.D., Ingram Assistant Professor of Cancer Research and director of Cancer Health Informatics and Strategy, pictured here.

“As physicians we are all generating massive amounts of data about patients and the genetic mutations in their tumors, along with patient response to medications and other treatments. But much of that data is kept in silos and has not been shared. AACR Project GENIE is one of the first efforts to make some of this data available for cancer researchers so that we can accelerate the pace of discovery,” Levy said.

Click here to read more.

Helping Cancer Patients Through Psycho-Oncology, by CEO Laura Heatherly

AAEAAQAAAAAAAAQvAAAAJDc2Nzc3ZWRmLWFjZTItNDRhNS1hYmUxLWE0YWMxOTg1YWE2ZgRecently in the New York Times, I read an article written by Susan Gubar regarding her bout with cancer and dealing with occupational therapy.  Basically, after eight years of physical therapy, she felt that she had not received any professional assistance for many of the issues that come with being diagnosed with cancer such as fear, weakness, fatigue, insomnia, etc.

Each year 12.7 million people discover they have cancer which is one of the most mysterious and terrifying diseases in our lifetime.  Thanks to research, scientists work round the clock to find new discoveries that will turn into clinical trials and new drug discoveries that will save lives.  However, patients are living daily with fear – the fear of dying, fear of coping with the disease while taking care of their families, fear of the unknown and more.

Thanks to Dr. Jimmie C. Holland who is the Wayne E. Chapman Chair in Psychiatric Oncology at Memorial Sloan Kettering Cancer Center in New York, she pioneered ways in which counseling, psychosocial interventions, and medications can reduce the distress experienced by cancer patients and their families.  As a psychiatrist for more than 30 years, Dr. Holland has devoted her career to helping patients, their families, and medical staff as they cope with the psychological burden of cancer and its treatment.

The T.J. Martell Foundation has been supporting psychiatric oncology at Memorial Sloan Kettering Cancer Center for many years and has navigated patients to getting the help they need to be able to deal with their disease.  Our goal is to create positive energy in hopes that patients can overcome their fear and anxiety and tackle their disease.

Believe me, Dr. Jimmie Holland is a pioneer – she is from my home state of Texas and she is one of the best people that I know who are helping to change the world in the way we deal with cancer .

We are Proud of our Commitment to Excellence

BlogThe T.J. Martell Foundation has contributed to many scientific achievements in leukemia, cancer and AIDS research over the past forty years. We are also focused on funding the brightest minds that will be the leaders in scientific research of tomorrow.

To read more about the life-saving research we are funding with your support, please click here.

New Blood Test Shows Promise in Cancer Fight

In the usual cancer biopsy, a surgeon cuts out a piece of the patient’s tumor, but researchers in labs across the country are now testing a potentially transformative innovation. They call it the liquid biopsy, and it is a blood test that has only recently become feasible with the latest exquisitely sensitive techniques. It is showing promise in finding tiny snippets of cancer DNA in a patient’s blood.

“Liquid biopsies offer real promise. Sometimes even the tissue biopsy obtained by the surgeon can fail to show the mutation which will predict that a patient will have a good response to a targeted agent. Indeed, liquid biopsies may allow oncologists to predict the emergence of drug resistance even before a tumor grows on x-rays. A formidable new technology,” says Dr. Gregory Curt, Chairman of the T.J. Martell Foundation’s Scientific Advisory Committee.

For the full article in The New York Times, please click here.

Gene Mutations May Predict Melanoma Response to Immunotherapies

Douglas Johnson, M.D.

Christine Lovly, M.D., Ph.D.

Melanoma patients whose tumors test positive for mutations in the NRAS gene were more likely to benefit from new immunotherapy drugs, according to a new study led by Vanderbilt-Ingram Cancer Center (VICC) investigators.

Douglas Johnson, M.D., assistant professor of Medicine, and Christine Lovly, M.D., Ph.D., assistant professor of Medicine and Cancer Biology, are co-first authors of the study, conducted in conjunction with colleagues from Memorial Sloan Kettering Cancer Center (MSKCC), New York, and Massachusetts General Hospital (MGH), Boston. The study was funded in part by the T.J. Martell Foundation and published in Cancer Immunology Research.

“We studied a small group of patients but the results were quite suggestive,” Johnson said. “This study highlights the need to find predictive markers that can help us understand which patients will respond to therapy.”

To read more, please click here.

Prostate Cancer Breakthrough at Mount Sinai Hospital

T.J. Martell Foundation-supported scientists have identified a “master regulator” gene driving aggressiveness in prostate cancer.

Scientists at Mount Sinai Hospital in New York, with the support of the T.J. Martell Foundation, have discovered a gene that acts as a switch and activates the aggressiveness of tumor cells. The discovery could have a major impact on the development of treatments for prostate cancer.

Prostate cancer is the most common tumor and one of the leading causes of cancer death in men. In about 10-15% of patients prostate cancer has an aggressive disease course characterized by the appearance of tumors in distant organs (metastasis) and the acquisition of resistance to anticancer drugs, which contributes to the death of most patients with prostate cancer.

The study, led by Dr. Josep Domingo-Domenech published and highlighted in the cover of the prestigious scientific journal Cancer Cell, describes a mechanism by which prostate cancer cells become aggressive and survive standard treatment. The key is a gene called GATA2, which encodes a transcription factor capable of reprogramming and activating aggressive cells through activation of multiple signaling pathways.

Using computational biology techniques that integrate genetic information from prostate cancer cells in humans and experimental models it has been possible to identify the master regulator gene GATA2. It was observed that experimental prostate cancer tumor cells with high levels of GATA2 initiated aggressive tumors that were resistant to chemotherapy. GATA2 gene acts as a master gene, controlling the activation and expression of many other genes. It activates other genes, putting them to work invading healthy tissue and initiating metastasis. Other genes are set to activate survival pathways that help initiate tumors and make cells resistant to anticancer drugs. This is the case for the gene coding the growth factor IGF2, which is activated directly by GATA2 triggering a signaling cascade that increases tumor cell survival under adverse conditions.

Importantly the discovery of the master gene, GATA2, that regulates expression of IGF2 led to the identification of a new therapeutic strategy for patients with prostate cancer. The new treatment strategy combines chemotherapy with IGF2 pathway inhibitors which improves the results of chemotherapy and allows more durable responses. Dr. Domingo- Domenech explains, ‘the combination of chemotherapy with IGF2 pathway inhibitors helps enhance the antitumor effect of chemotherapy and was well tolerated in animal models. Now we are looking forward to translate these studies into patients.”

“This important finding is a clear example of the excellent science with important clinical implications for cancer patients that the T.J. Martell Foundation is currently funding,” says Dr. James Holland, the founding research scientist for the T.J. Martell Foundation. The support that the T.J. Martell Foundation has given Dr. Domingo- Domenech during the last years is helping enormously to uncover new therapeutic targets against this devastating disease.

 

PALB2 Gene Mutation Affects Breast Cancer Risk

Having a family history of breast cancer nearly doubles a woman’s risk of developing the disease and genetic factors are known to play a major role in the origin of breast cancer.

The BRCA1 and BRCA2 genes were identified as major breast cancer susceptibility genes nearly 30 years ago and it is estimated that these gene mutations explain about 50 percent of familial breast cancer cases.  BRCA1 and BRCA2 mutation tests have been widely used in high risk women (e.g., women with a strong family history of breast cancer) for risk assessment and management which may include prophylactic surgical and drug therapy intervention.

However, a significant fraction of familial breast cancer cases remain unexplained. A recent study identified the PALB2 gene as another major breast cancer predisposition gene. The PALB2 (Partner and localizer of BRCA2) gene produces a protein that is crucial for key BRCA2 functions. Mutation carriers of this gene were found to have a 35 percent risk of developing breast cancer by the age of 70, triple the risk seen in the general population.  For breast cancer diagnosed before age 40, having PALB2 mutations was related to an 8 to 9-fold increased risk.  It is estimated the PALB2 mutations explain about 2 to 3 percent of familial breast cancer risk. This study expanded our knowledge of genetic contributions to the familial profile of breast cancer.

Currently, the benefit and risk of deploying preemptive measures like surgery or drug therapy based on PALB2 mutation status is unknown. While the utility of applying PALB2 mutation information for risk management of high risk populations needs to be further investigated, individuals with known mutations of this gene are encouraged to seek genetic counseling because PALB2 mutations are also known to increase the risk of pancreatic cancer and may increase the risk of ovarian cancers. Mutations in PALB2 are very rare in the general population. Thus, screening for PALB2 in the general population appears to be unnecessary.

Xiao Ou Shu, M.D., Ph.D., MPH
Ingram Professor of Cancer Research
Vanderbilt-Ingram Cancer Center

HPV-Positive Head and Neck Cancer Patients May be Safely Treated with Lower Radiation Dose

A new study suggests that lowering the dose of radiation therapy for some head and neck cancer patients may improve outcomes and cause fewer long-term side effects.

The research was presented by lead author Anthony Cmelak, M.D., professor of Radiation Oncology at Vanderbilt-Ingram Cancer Center (VICC), during the 50th annual meeting of the American Society of Clinical Oncology (ASCO), held recently in Chicago.

The study focused on patients with newly-diagnosed oropharyngeal cancers related to the human papilloma virus (HPV). More than two-thirds of new head and neck cancer patients have HPV-positive tumors and the number of these patients is on the rise. Cmelak’s prior cooperative group study found that patients with HPV-positive oropharyngeal cancer have significantly longer survival rates than patients whose tumors are HPV negative.

For the new study, 80 HPV-positive patients with stage III, or IVa,b squamous cell cancer of the oropharynx received induction chemotherapy, including paclitaxel, cisplatin and cetuximab.

After chemotherapy, 62 of the patients showed no sign of cancer and were assigned to receive a 25 percent lower dose of intensity-modulated radiation therapy – an advanced technology that targets the radiation beam more accurately to treat the tumor without harming surrounding tissue. The rest of the patients received a standard IMRT dose. The drug cetuximab was also given to both groups of patients along with the IMRT treatment.

Two years after treatment, the survival for the low-dose IMRT patients was 93 percent.  Those who did not have complete resolution of cancer following induction and went on to get full-dose radiation had an 87 percent two-year survival. Eighty percent of the low-dose patients and 65 percent of standard IMRT patients also showed no evidence of tumor recurrence.  Ninety-six percent of those who had minimal or no smoking history had no evidence of tumor recurrence after two years following treatment, and long-term side effects were minimal.

The investigators concluded that patients with HPV-positive cancer who had excellent responses to induction chemotherapy followed by a reduced dose IMRT and cetuximab experienced high rates of tumor control and very low side effects particularly for those with a minimal smoking history.

Treating tumors in the delicate head and neck region often causes side effects that can be troublesome and long-lasting, including difficulty swallowing, speech impairment, dry mouth, problems with taste and thyroid issues, so any therapy option that reduces these side effects can have an impact on patient quality of life.

“Treatment for head and neck cancer can be quite grueling, so it’s very encouraging to see we can safely dial back treatment for patients with less aggressive disease and an overall good prognosis, particularly for young patients who have many years to deal with long-term side effects,” said Cmelak.

He noted that lower-dose IMRT is not recommended for patients with HPV-negative cancer or larger tumors.

The authors note that further studies of reduced-dose IMRT in HPV-positive patients are warranted.

Other investigators include Jill Gilbert, M.D., VICC; Shuli Li, Ph.D., Dana Farber Cancer Institute, Boston, Massachusetts; Shanthi Marur, M.D., William Westra, M.D., Christine Chung, M.D., The Johns Hopkins University School of Medicine, Baltimore, Maryland;  Weiqiang Zhao, M.D., Ph.D., Maura Gillison, M.D., Ph.D., The Ohio State University, Columbus, Ohio; Julie Bauman, M.D., Robert Ferris, M.D., University of Pittsburgh Cancer Institute; Lynne Wagner, Ph.D., Feinberg School of Medicine, Northwestern University, Chicago, Illinois; David Trevarthen, M.D., Colorado Cancer Research Program, Denver;  A. Demetrios Colevas, M.D., Stanford University, California; Balkrishna Jahagirdar, M.D., HealthPartners and Regions Cancer Care Center, St. Paul, Minnesota;  Barbara Burtness, M.D., Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Funding was provided by The National Cancer Institute, a division of the National Institutes of Health (CDR0000665170).

 

Excerpt: Colon Cancer Screening Saves Lives

Widespread screening for colorectal cancer has helped prevent an estimated half-million cases of the disease since the mid- 1970s, a new study suggests.

At a time when screening for many kinds of cancer is being questioned, the findings underscore the importance of screening for colorectal cancer in saving lives, said the senior author of the study, Dr. James Yu, an assistant professor of therapeutic radiology at Yale School of Medicine.

Colonoscopies, beginning at age 50, are considered the gold standard in colon cancer screening, although other techniques, like fecal occult blood testing, can detect some cancers.

 To read the full article in The New York Times, please click here.