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.

 

Rest In Peace

This weekend, longtime beloved ESPN anchor Stuart Scott lost his third bout with cancer, leaving behind two beautiful daughters and countless friends, family members, colleagues and fans across the country. He faced cancer with bravery and inspired many who also face the disease.

So today we choose to honor him by sharing what we think is his most touching quote about cancer and life: ”When you die, it does not mean that you lose to cancer. You beat cancer by how you live, why you live and the manner in which you live.”

Stuart Scott was 49, and his journey through cancer treatment was detailed in The New York Times. “Over the years, he entertained us, and in the end, he inspired us — with courage and love. Michelle and I offer our thoughts and prayers to his family, friends, and colleagues,” said President Obama.

Congratulations are in Order!

Every year Billboard releases its prestigious list of Women In Music: The Most Powerful Executives in the Industry, and every year several of our board members are included for being “ground-breakers and game changers.” This year our board members Jody Gerson, Julie Swidler, Jennifer Breithaupt and Sharon Dastur as well as our New York Honors Gala honoree Marsha Vlasik were all listed. We are so honored to work with these incredibly hard-working women to continue our vital leukemia, cancer and AIDS research.

To read the full list, please visit billboard.com.

Guest Blog Post: Important Advice if You’re Considering Mastectomy

Ingrid Meszoely, M.D. is Associate Professor of Surgical Oncology and Clinical Director, Vanderbilt Breast Center at Vanderbilt-Ingram Cancer Center.

Following the completion of several large studies in the late 1980s and early 1990s involving thousands of women, it was clearly determined that the number of years a woman lived following breast cancer surgery was exactly the same whether she underwent mastectomy (removing the whole breast) or lumpectomy (just removing the part  of the breast with the cancer). This was a big breakthrough for breast cancer treatment with the realization that more surgery doesn’t result in better outcomes.  Initially this resulted in a trend of women choosing lumpectomy over mastectomy in order to preserve their breasts.

However in recent years, as Dr. Kummerow and many other researchers have found, there is a nationwide trend in choosing mastectomy over lumpectomy despite there being no clear survival advantage.  In addition, many women choose to undergo mastectomy of the non -affected breast despite the fact that the risk of developing cancer in this breast is very low and that it does not have any effect on survival from their current breast cancer.

As a breast cancer surgeon, I see this same phenomenon in my own practice.  The choice of mastectomy on one or both sides is often driven by multiple factors including the fear of cancer coming back or a new cancer on the other side and the wish to do everything one can to prevent this.  This often provides some sense of control and peace of mind in the setting of an overwhelming diagnosis.

When a woman is diagnosed with early breast cancer and given the choice of mastectomy or lumpectomy because she is a candidate for either procedure, the options should be considered carefully.

It should be clearly recognized that mastectomy does not provide 100 percent protection from cancers coming back. Cancers often come back at other sites outside of the breast before they return in the area of the removed breast tissue.  Because mammograms or other imaging studies are not routinely used after mastectomy, the finding of recurrences along the chest depends on continued routine self -exam and clinical exam by their doctor when the tumor is large enough to feel as opposed to being detected on mammogram when it is very small.

Mastectomy is also associated with increased complications compared to lumpectomy and these are often related to the reconstruction, which can be discouraging.  It is even more devastating when there are complications related to the unaffected breast when women choose mastectomies on both sides.

Lymph node surgery often is performed in the setting of mastectomy.  If just a single lymph node is found to be involved with breast cancer, removal of additional lymph nodes is recommended which can result in added complications. However if a lumpectomy is chosen, generally 3 or more lymph nodes need to be involved with cancer before more lymph nodes are removed.

When a woman presents with newly diagnosed early breast cancer and is put in the position of making a decision between lumpectomy and mastectomy, a thoughtful discussion should be initiated with her treating physicians.  Ultimately, the decision is very personal and she should choose the procedure that suits her lifestyle and provides her with the greatest sense of wellbeing.

 

The Power of Philanthropy: Reducing the Burden of Breast Cancer

The longstanding history between the T.J. Martell Foundation and Vanderbilt-Ingram Cancer Center underscores the power of philanthropy in reducing the burden of cancer. While we celebrate the many advances that result from these powerful partnerships, we know that continued support will position us to make new discoveries that change the course of cancer for patients and families throughout the world.

Increases in cancer cure and survivorship over the past 30 years showcase the impact of discovery on cancer care. In 1971, one in 69 people was a cancer survivor, and a total of three million survivors lived in the United States. In 2012, one in 23 people is a cancer survivor, accounting for a national total of 13.7 million survivors. The collective efforts of all who fight cancer are responsible for these life-saving victories.

While these snapshots of progress are encouraging, malignant disease will continue to be common—and in need of directed treatment—for many years to come. Currently, between 35 percent and 40 percent of oncology treatment is genetically directed. While this represents an enormous increase over the last several decades, this figure also shows the potential and need for continued research and therapeutic discovery. This year alone, 1.6 million Americans will receive a new cancer diagnosis. The pace of discovery impacts the type of care each of these individuals will receive.

As we look to the future, to our ability to contribute to prevention, to develop new therapies and to use existing therapies in new ways, we are mindful of the enduring support we receive from our philanthropic partners. Without the strategic investments made by the T.J. Martell Foundation, Vanderbilt-Ingram’s ability to advance our understanding of cancer and impact patients’ lives would be distinctly different.

Dr. Jennifer Pietenpol of the Vanderbilt-Ingram Cancer Center

A major focus of research in the laboratory of Jennifer A. Pietenpol, Ph.D., is to define molecular changes that are frequent in breast cancer cells and to use bench-based discoveries to advance patient care.  Treatment of patients with triple negative breast cancer (TNBC) has been challenging due to the heterogeneity of the disease and the absence of well-defined molecular drivers amenable to targeted therapies. Thus, identification of predictive biomarkers is critical to select patients for more precise therapies against TNBC.  For the past several years, Dr. Pietenpol’s group has been integrating their expertise in molecular genetics, with bioinformatic analyses of high dimensional genomic data sets, to molecularly sub-classify difficult-to-treat TNBC.   They have  been identifying and validating molecular ‘drivers’ involved in different types of TNBC as well as using the information gained to benefit patients and to generate the next set of hypotheses that  they are testing at the bench.

Dr. Vandana Abramson of the Vanderbilt-Ingram Cancer Center

The laboratory will continue to investigate novel therapeutic approaches based on the genetic and biological underpinnings of TNBC.  They are very grateful for the T.J. Martell Foundation support and, in particular the recent support through the Martina McBride Cancer Research Fund as it has enabled a highly productive collaboration with Dr. Vandana Abramson, a leading medical oncologist specializing in breast cancer at Vanderbilt-Ingram.  The cross-disciplinary collaboration is allowing for more rapid advancement of pre-clinical data from the bench to the clinic and thus, alignment of patients to molecularly targeted therapy.

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.