AACR, Author Interviews, Duke, Immunotherapy / 14.11.2015

MedicalResearch.com Interview with: Jiayuh Lin, Ph.D. Associate Professor, College of Medicine, The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Jiayuh Lin: Pancreatic cancer is one of the most serious forms of cancer.  Because of the poor response to chemotherapy as conventionally used, patients with any stage of pancreatic cancer may appropriately be considered candidates for clinical trials using novel agents. IL-6 signaling plays an important role in oncogenesis and high serum IL-6 levels is a poor prognostic factor for overall survival in pancreatic cancer. Therefore, IL-6 is considered as a viable target for pancreatic cancer therapy.  We utilized a drug discovery method with Multiple Ligand Simultaneous Docking and drug repositioning to identify an existing FDA-approved drug Bazedoxifene with previously unknown biological function as an IL-6/GP130 inhibitor.  Bazedoxifene can inhibit cell viability of pancreatic cancer cells expressing IL-6 and suppressed pancreatic tumor growth in vivo. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.11.2015

MedicalResearch.com Interview with: Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868  Medical Research: What is the background for this study? What are the main findings? Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options.  This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types.  Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes. In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain.  This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth.  However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient.  Thus, finding this change is important and may be able to guide a more personalized therapy choice.  Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers.  A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer. (more…)
Author Interviews, Breast Cancer, Chemotherapy, MRI / 14.11.2015

MedicalResearch.com Interview with: Dr. Franca Podo, Dr Sci Former Director of the Molecular and Cellular Imaging Unit Department of Cell Biology and Neurosciences Istituto Superiore di Sanità Rome, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Podo: Population-based studies showed that triple negative breast cancers (TNBCs), i.e. those which are negative for estrogen and progesterone receptors without HER-2/neu overexpression, have a more aggressive clinical course and a 2-to-3 fold higher likelihood of distant recurrence and death from breast cancer within 5 years from diagnosis, compared with non-TNBCs. In a study published in Clinical Cancer Research (Online First 26 October 2015) Dr. F. Podo and Dr. F. Santoro (Istituto Superiore di Sanità, Rome) and Prof. F. Sardanelli (Università degli Studi di Milano, IRCCS Policlinico San Donato) in collaboration with other Italian co-authors, compared phenotype features and survival rates of invasive TNBCs versus non-TNBCs detected during the HIBCRIT-1 screening study of 501 asymptomatic women at high genetic-familial risk for breast cancer. The screening included BRCA1 and BRCA2 mutation carriers, as well as women with a strong family history of breast and/or ovarian cancer, enrolled between 2000 and 2008 in 18 centers. Data analysis from a median 9.7-year follow-up until June 2015 showed that, combining an annual screening including magnetic resonance imaging (MRI) with adequate treatment options, the mean 5-year overall survival of triple negative breast cancers was not significantly different from that of non-TNBCs (86% vs 93%), in spite of a 3-fold higher rate of cases of grade 3 invasive ductal carcinoma in the former subgroup (71% in TNBCs vs 23% in non-TNBCs). The mean disease-free survival rates were also very similar (77% vs 76%, respectively). (more…)
AACR, Author Interviews, NIH, Nutrition, Ovarian Cancer, Race/Ethnic Diversity / 13.11.2015

MedicalResearch.com Interview with: Bo (Bonnie) Qin, PhD Postdoctoral associate at Rutgers Cancer Institute of New Jersey Medical Research: What is the background for this study? What are the main findings? Response:  Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments. We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women. (more…)
Author Interviews, Dermatology, Melanoma, NEJM, UCSF / 13.11.2015

MedicalResearch.com Interview with: Boris C. Bastian, MD, PhD Professor of Dermatology and Pathology Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Bastian:  The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers. Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case. Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma. (more…)
AACR, Author Interviews, Lymphoma, MD Anderson / 12.11.2015

MedicalResearch.com Interview with: Dr. Jatin J. Shah, MD Associate Professor, Department of Lymphoma/Myeloma Assistant Professor, Lymphoma/Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Houston, TX  Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells. The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, PNAS / 12.11.2015

MedicalResearch.com Interview with: Lei Xu, MD, PhD Steele Laboratory of Tumor Biology Radiation Oncology Department Massachusetts General Hospital Medical Research: What is the background for this study? Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing. Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves. (more…)
AACR, Author Interviews, Biomarkers, Chemotherapy, Colon Cancer, MD Anderson / 10.11.2015

MedicalResearch.com Interview with: Van K. Morris,  M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030  Medical Research: What is the background for this study? What are the main findings? Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy. For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples. (more…)
AACR, Author Interviews, Breast Cancer / 10.11.2015

MedicalResearch.com Interview with: Aditya Bardia MD, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School, Boston, MA 02114  Medical Research: What is the background for this study? What are the main findings? Dr. Bardia: Triple negative breast cancer (TNBC) represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20% of all invasive breast cancers and is more prevalent in young and African-American women.Triple negative breast cancer characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. Trop-2 is a protein present in limited amounts in normal human tissues but widely found in many human cancers. It is expressed in more than 80 percent of Triple negative breast cancer, making it an attractive therapeutic target. Sacituzumab govitecan (IMMU-132) is a first-in-class ADC developed by Immunomedics, Inc. by linking moderately-toxic drug, SN-38, to an antibody that binds to the Trop-2 target found in many solid cancers. We conducted a clinical trial with this drug for patients with advanced tumors, including patients with TNBC who either had failed their previous treatments for Triple negative breast cancer or their cancer had returned. We have found that even though patients who participated in this trial had very advanced stages of the disease, approximately 30% of these patients responded with 30% or more tumor shrinkage. The response rate to standard agents is usually 10 to 20 percent, while the response rate with IMMU-132 was approximately 30 percent. If you include patients with stable disease, the clinical disease control rate, which is complete response [CR] + partial response [PR] + stable disease, was about 75 percent. (more…)
AACR, Author Interviews, Cancer, Cancer Research, University Texas / 10.11.2015

MedicalResearch.com Interview with: Xifeng Wu, M.D., Ph.D, Professor, Epidemiology Stephanie Melkonian, Ph.D University of Texas M. D. Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Response: This study examines dietary intake of meat-cooking mutagens and genetic risk factors associated with kidney cancer in a population of 659 kidney cancer patients and 699 matched healthy control subjects from the community. We calculated the intake of several cancer-causing carcinogens that are produced when certain types of meat are cooked over an open flame and at high temperatures resulting in the burning, smoking or charring of the meat (for example, during barbequing or pan-frying). We found that kidney cancer patients consumed more red and white meat when compared to the healthy individuals, and also had higher intake of these cancer-causing chemicals created through the meat cooking process. These results suggest that meat intake, and the way we cook our meat, may potentially be linked to risk of kidney cancer. Additionally, we found that individuals with certain genetic variants were more likely to be susceptible to the harmful effects of the cancer-causing mutagens created during the process of cooking meat. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research / 10.11.2015

Dr. Priscilla Kaliopi Brastianos MD Instructor, Medicine, Harvard Medical School Assistant Physician in Medicine Hematology/Oncology, Massachusetts General HospitalMedicalResearch.com Interview with: Dr. Priscilla Kaliopi Brastianos MD Instructor, Medicine, Harvard Medical School Assistant Physician in Medicine Hematology/Oncology, Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Response: Craniopharyngiomas are rare brain tumors that can cause serious problems because of their location near critical structures in the brain, such as optic and other cranial nerves, the pituitary gland and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues. In addition, since the tumor adheres to these nearby critical structures, complete removal is difficult, which can lead rapid recurrence. Medical therapies have not been effective for craniopharyngiomas, namely because we did not understand the molecular underpinnings of these tumors. Last year, we performed genomic characterization of craniopharyngiomas, with the goal to identify potential therapeutic targets. We were surprised to find that nearly all papillary craniopharyngiomas have BRAF mutations, which are the same mutations that have been found in melanoma. We recently had the opportunity to translate our results to the clinic. A 38 year old patient presented to our institution, requiring 4 urgent neurosurgeries in 2 months for his papillary craniopharyngioma. When we presented a fifth time, we treated him with a therapy that targets his BRAF mutation. After just 4 days of therapy, his tumor had shrunk by nearly 25%. Similar to what is done in BRAF mutant melanoma, we added a MEK inhibitor to his treatment. By day 34 of therapy, his tumor was more than 80% smaller. We  also detected the BRAF mutation in this patient’s blood. (more…)
Author Interviews, Cancer Research, Endocrinology, Journal Clinical Oncology, Menopause, NIH / 07.11.2015

MedicalResearch.com Interview with: Elizabeth K. Cahoon, PhD Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Cahoon: Although basal cell carcinoma (BCC) is the most common cancer in the United States, there is relatively little research on risk factors since few population-based cancer registries do not capture information on this malignancy. Sun exposure (in particular ultraviolet radiation) is the primary risk factor for basal cell carcinoma, but less is known about other factors that may affect this risk. A previous study found a relationship between menopausal hormone therapy (MHT) use and increased risk of BCC in a population of Danish women. In our study we looked to see if factors related to estrogen exposure from multiple sources was associated with basal cell carcinoma risk in a large, nationwide, prospective study. These included use of oral contraceptives or menopausal hormone therapy, but also reproductive factors (like age at menarche and menopause). We observed that women who experienced natural menopause later in life were more likely to develop basal cell carcinoma compared to women who had natural menopause at a younger age. In addition, women who reported using menopausal hormone therapy for one year or longer were more likely to develop basal cell carcinoma compared to women who did not report MHT use. Women who reported natural menopause and menopausal hormone therapy use for 10 or more years had the highest risk of basal cell carcinoma, compared to women with no menopausal hormone therapy use. (more…)
Author Interviews, Breast Cancer, Education, NYU, Radiology / 06.11.2015

MedicalResearch.com Interview with: Jiyon Lee, M.D. Assistant Professor of Radiology, NYU School of Medicine NYU Cancer Institute, Breast Imaging Center New York, New York 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Lee:   Even before the USPSTF changed their breast screening guidelines in 2009, I conducted community outreach to help educate others on my area of expertise, breast imaging and breast screening. I presented lay friendly, illustrated, and practical explanations in a structured talk, about the big picture and the salient details, in a way that I would want if I were not a breast radiologist. As is customary for such community outreach, we solicited feedback from attendees. It was gratifying to hear the positive responses. That they wished for such education for others served as a clarion call that is understandable. Education should be objective and noncoercive.  “Knowledge is power,” but only if complete and accurate. Breast cancer is still a common disease, we are all at least at average risk, and screening is still standard of care.  Much of the debate surrounding screening mammography centers on the age of onset of screening and the optimal screening interval. The USPSTF states that shared-decision making between women and their providers may occur, especially for women in 40-49 year group.  But the TF does not stipulate when or how or by whom this talk will ensue, and notice that their guidelines refer to film mammography, and “biennial” mammography. Since the time of this manuscript, the American Cancer Society issued new guidelines on 10/20/2015 that among its bullet points emphasized annual mammography for women 45-54 years and deemphasized clinical breast exam, while supporting option to start annually at age 40 with shared decision making to weigh what are referred to as “risks” and benefits. Although the fine print does reaffirm that annually starting at age 40 is the screening model that saves the most lives, the ACS is encouraging deliberate value judgment regarding “risks” and “harms.” Their fine print is also intimating that women 55 and over have nondense tissue and that their cancers are indolent. The ensued publicity and mixed messaging have caused another cycle of confusion regarding breast cancer screening. As the experts in this field of image-based screening, radiologists have opportunity to clarify and contextualize the issues and details of the screening discussion, and can do so with objectivity, respect for all sides of the debate, and compassion. All responsible ways to continually educate both women and all providers will enable both sides to engage in the discussion fairly. Because as we discourage paternalistic medicine and promote shared decision making, it’s not fair play if all responsible sides do not get fair say. Do realize that not all women see providers regularly, and depending on the medical subspeciality, not all providers are mentioning screening til women reach a certain age and may not relay importance of the physical exam components that complement imaging. This article specifically highlights how such direct and interactive public education can effect potential benefit in two ways.
  • First, directly reduce one of the core criticisms about screening: the “anxiety” that women may experience, which is heavily weighed as a “harm” of screening.  Most women do not experience high anxiety, and are glad to have a test that may help them. And education can help demystify much of the process and protocol, and explain up to what may be that patient’s next test results if she engages in screening at all. No one can tell that.
  • Two, education can directly increase one of the necessary components of shared decision making that is presumed in implementing breast screening: informing women. The pre- and post-lecture questionnaire, along with fact-based quiz questions, provided insight and enabled learning opportunity for the audience that are not usual for community outreach.  Education that keeps on going—and is shareable!-- after the lecture is done.
Author Interviews, Melanoma, OBGYNE / 06.11.2015

MedicalResearch.com Interview with: Pedram Gerami, MD Department of Dermatology Northwestern University Chicago, IL Medical Research: What is the background for this study? What are the main findings?   Dr. Gerami: The influence of pregnancy on the prognosis of melanoma has been debated for decades. Even in the last ten years, population-based and cohort studies have given us mixed results, with some suggesting no adverse influence of pregnancy, and others reporting poorer outcomes and increased cause-specific mortality. The conflicting data leave many clinicians uncertain of how to advise patients to proceed with family planning after a diagnosis of melanoma. Since one-third of all new cases of melanoma diagnosed in women will occur during childbearing age, this represents a fairly common clinical dilemma for physicians and their patients. We suspected that the different results from different investigators maybe related to the melanoma stage of the patients being studied. We investigated the impact of pregnancy on tumor proliferation in women with primarily early stage melanoma. In comparing melanomas from a group of women with pregnancy-associated melanoma (PAM) and a non-PAM group, we found that women with pregnancy-associated melanoma  actually had a significantly greater proportion of in situ disease, and for cases of invasive melanoma there was no significant difference in proliferative activity, as assessed by mitotic count or two immunohistochemical markers of cell proliferation. In a comparison of additional prognostic features such as Breslow depth and ulceration, we found no significant differences between groups to suggest more aggressive tumor behavior in association with pregnancy. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Immunotherapy, NEJM / 05.11.2015

MedicalResearch.com Interview with: Toni Choueiri, MD Clinical Director, Lank Center for Genitourinary Oncology Director, Kidney Cancer Center Senior Physician Dana Farber Cancer Institute Associate Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Choueiri: In the METEOR trial, we aimed to compare cabozantinib, a novel VEGFR, MET, AXL inhibitor to everolimus, a standard 2nd line option in advanced RCC. There is an unmet in this setting. Cabozantinib resulted in a median PFS of 7.4 months compared to 3.8 months with everolimus. Responses also were 4-times higher with cabozantinib-treated patients. At the interim OS analysis, there was a strong trend favoring cabozantinib.  (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson / 05.11.2015

MedicalResearch.com Interview with: William N. William Jr., MD Associate Professor Chief, Head and Neck Section Department of Thoracic / Head and Neck Medical Oncology The University of Texas M. D. Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. William: Oral pre-malignant lesions are often characterized as white and/or red patches in the mouth and are considered risk factors for oral cancer. This is why it might be best for people to go get oral cancer screening done if they suspect that there might be a problem. However, not all oral pre-malignant lesions will turn into cancer, but when this happens, surgery is usually recommended, many times leading to serious speech and swallowing dysfunction. Chemoprevention is the use of compounds to prevent cancers from happening before they occur. One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk. The Erlotinib Prevention of Oral Cancer (EPOC) trial involved 379 patients at five sites across the country. All had premalignant lesions in their mouths. Following study enrollment, participants were evaluated for LOH, a chromosomal abnormality characterized by the loss of chromosomal regions, which include tumor suppressor genes. Patients who tested positive for LOH were considered to be at high risk for oral cancer and were randomized to receive either erlotinib (an EGFR inhibitor drug) or a placebo for one year. The study’s primary endpoint was to determine if fewer patients treated with erlotinib would develop oral cancer, compared to those that received placebo. The EPOC study demonstrated that LOH predicted a higher oral cancer risk. LOH-negative patients had a three-year cancer-free survival rate of 87 percent compared to 74 percent for the LOH-positive group. However, patients who took erlotinib showed no statistical difference in terms of cancer-free survival rates after three years: 74 percent for participants given erlotinib compared to 70 percent for those taking placebo. Patients with both LOH and EGFR copy number gains had the highest incidence of cancer, but still did not benefit from erlotinib. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA / 05.11.2015

MedicalResearch.com Interview with: Dr. Brad A. Bryan Ph.D Assistant Professor Biomedical Sciences Texas A&M University Health Science Center, Houston, TX Department of Biomedical Sciences Texas Tech University Health Sciences Center Medical Research: What is the background for this study? What are the main findings? Dr. Bryan: In 2008 it was serendipitously discovered that the beta blocker propranolol was effective in treating a common benign pediatric vascular tumor called infantile hemangioma.  Over the past few years, my lab has been working on elucidating the molecular mechanisms underlying this pediatric tumor and part of this research involved uncovering how propranolol selectively inhibited these tumors.  At the same time these studies were taking place, other members of my lab were working on pre-clinical drug development for a malignant vascular tumor called angiosarcoma.  Patients with angiosarcoma are faced with very few effective treatment options and abysmal survival rates, so we decided to see if the efficacy of beta blockade observed in infantile hemangiomas transferred to angiosarcomas.  Using preclinical in vitro and in vivo assays, we demonstrated that propranolol was very effective at inducing cell death, blocking migration, and inhibiting tumor growth in our angiosarcoma models.  This work was subsequently published in Plos One (Stiles et al., 2013).  I then collaborated with Dr. William Chow from San Francisco to test propranolol off-label (propranolol is FDA approved to treat high blood pressure, heart dysrhythmias, thyrotoxicosis, and essential tremors) in a patient suffering from a rapidly expanding angiosarcoma covering a large portion of his face.  In the window between diagnosis of the tumor and the start of chemotherapy, we placed the patient on oral propranolol.  The redness of the tumor very rapidly lessened and remarkably by only one week of treatment the tumor margins appeared to significantly shrink.  We examined biospies of the tumor before and after only one week of propranolol and found that the proliferation of the tumor cells was markedly decreased following beta blockade.  After a combination of propranolol, chemotherapy, and radiation that lasted several months, the patient had no detectable metabolically active tumor or distant metastases. We published these findings in JAMA Dermatology (Chow et al., 2015). (more…)
Author Interviews, Breast Cancer / 05.11.2015

MedicalResearch.com Interview with: Shirley Mertz President of the US Metastatic Breast Cancer Network (Ms. Mertz has been living with metastatic breast cancer since 2003) Medical Research: What do you mean by the term, "Long Term Responders"? How is this different than "Survivor"? Shirley Mertz: For many years, especially in the month of October in the U.S., the media and breast cancer organizations have written stories and celebrated women who have received an early stage breast cancer diagnosis, gone through treatment and now see breast cancer in their "rear view mirror." For these women (Stage I, II or III disease), treatment has an end and they can get on with their lives. In contrast, for patients diagnosed with Stage IV disease, also called metastatic breast cancer, treatment never ends and they will ultimately succumb to the disease. Long term responders are those metastatic breast cancer patients who have responded well to a treatment--experiencing perhaps a complete remission (not a cure) or stable disease. While that treatment may continue to keep their disease under control for 5 or more years, such patients must continue with treatment. Ultimately, their disease will progress and they will die of the disease. This can be immensely traumatic for the patient and the family if they were failed to be diagnosed by a doctor. If the cancer was found sooner then there would be a better chance of survival. If this has ever happened to you then you may want to contact a failure to diagnose attorney. (more…)
Author Interviews, Breast Cancer, Diabetes / 05.11.2015

MedicalResearch.com Interview with: Dr Nicoletta Provinciali, MD Oncologist from the E.O. Ospedali Galliera Genoa, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Provinciali: We know that higher insulin levels have been associated with a worse prognosis in early breast cancer patients. In this study we wanted to evaluate the impact of insulin resistance on metastatic breast cancer patients receiving first line chemotherapy. We found that insulin resistance status together with the endocrine status had an adverse prognostic effect. (more…)
Author Interviews, Chemotherapy, Lymphoma, NEJM / 04.11.2015

Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021MedicalResearch.com Interview with: Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021   Medical Research: What is the background for this study? What are the main findings? Dr. Ruan: Mantle cell lymphoma is an uncommon subtype of non-Hodgkin lymphoma that primarily affects elderly populations. Conventional chemotherapy regimens are generally not curative, and may not be tolerated by many patients, underscoring the need for treatment alternatives.  Previous experience with immunomodulatory compound lenalidomide has shown favorable activity and was well tolerated in patients with relapsedMantle cell lymphoma.  We evaluated the efficacy and safety of the biologic combination with lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma (MCL). The main findings of the study showed that the combination was effective and generally well tolerated when given as induction and maintenance treatment. The overall response rate was 92%, with complete response rate of 64% in the 36 evaluable patients. Median duration of response has not been reached at a median follow up of 30 months.   Treatment was outpatient-based and quality-of-life was preserved for most patients. (more…)
Author Interviews, Cancer Research, Personalized Medicine / 04.11.2015

Timothy Humphrey DPhil. CRUK/MRC Oxford institute for Radiation Oncology University of Oxford, UKMedicalResearch.com Interview with Timothy Humphrey DPhil. CRUK/MRC Oxford institute for Radiation Oncology University of Oxford, UK Medical Research: What is the background for this study? What are the main findings? Response: Multiple mutations resulting in loss of a particular histone mark (H3K36me3) are frequently found in a number of cancer types. These include mutations resulting in loss of the tumour suppressor SETD2 (which trimethylates H3K36) and over-expression of the oncogene KDM4A (which demethylates H3K36me3), which together are observed in more than 10% of a number of cancer types. Notably, loss of H3K36me3 has been reported in more than 50% of pediatric high-grade gliomas. While loss of this histone mark is associated with poor prognosis, there is no targeted therapy yet. Following observations made in fission yeast, we have found a new way to selectively target H3K36me3-deficient cancers using the WEE1 inhibitor, AZD1775. Surprisingly, treatment of H3K36me3-deficient cancer cells with the WEE1 inhibitor resulted in S-phase arrest. Further analysis revealed ribonucleotide reductase to be the target of this synthetic lethal interaction, thereby leading to dNTP starvation, replication fork collapse and cell death. (more…)
Author Interviews, Cancer Research, Microbiome / 04.11.2015

MedicalResearch.com Interview with: Simba Gill Ph.D CEO, Evelo Therapeutics MedicalResearch: Evelo Therapeutics, a new company focuses on leveraging the power of the microbiome to develop novel therapies for cancer. Evelo is pioneering Oncobiotic™ therapeutics, a new modality in cancer therapy based on the cancer microbiome. Dr. Gill, CEO of  Evelo Therapeutics began his career at Celltech, focused on antibody research. Dr. Gill earned his Ph.D. from King’s College, London, and his MBA from INSEAD. Medical Research:  What is a microbiome? How do microbiomes play a role in health and disease? Dr. Gill: The microbiome is the collection of trillions of bacteria, funguses, viruses and other microbes that live on and within the human body. There are different clusters of microbes in different parts of the body, including the skin, mouth, large intestine, and vagina. Recently we have learned that our microbial populations shift depending on changes to an individual’s health and wellness. The makeup of one’s microbiome has a strong influence on one’s health, immune response, and metabolic state. (more…)
Author Interviews, Biomarkers, Brigham & Women's - Harvard, Cancer Research / 03.11.2015

MedicalResearch.com Interview with: Bakhos A. Tannous, Ph.D Associate Professor of Neurology Harvard Medical School Director, Experimental Therapeutics and Molecular Imaging Lab Director, Interdepartmental Neuroscience Center Director, MGH Viral Vector Development Facility Massachusetts General Hospital Charlestown, MA 02129 Medical Research: What is the background for this study? What are the main findings? Dr. Tannous: In recent years, it has become apparent that, in addition to their role in promoting blood clotting, platelets take up protein and RNA molecules from tumors, possibly playing a role in tumor growth and metastasis. Working with our collaborators Dr. Thomas Wurdinger and Pieter Wesseling at the VU Medical Center, Amsterdam, the Netherlands, we found that the RNA profiles of tumor-educated platelets – those that have taken up molecules shed by tumors – can (1) distinguish healthy individuals and patients with six different types of cancer, (2) determine the location of the primary tumor and (3) identify tumors carrying mutations that can guide therapeutic decision making and personalized medicine. (more…)
Author Interviews, Cancer Research, Cognitive Issues, Journal Clinical Oncology, Memory / 03.11.2015

MedicalResearch.com Interview with: Dr Janette Vardy  BMed (Hons), PhD, FRACP A.Prof of Cancer Medicine University of Sydney Medical Oncologist ,Concord Cancer Centre Concord Repatriation & General Hospital Concord, Australia  Medical Research: What is the background for this study? Dr. Vardy: Many patients complain that their memory and concentration is not as good after chemotherapy.  Most of the studies have been in younger women with breast cancer, and are often limited by small sample sizes and short term follow up.    This is the largest longitudinal cohort study assessing impacts of cancer and its treatment on cognitive function. We evaluated changes in cognitive function in 289 men and women with localized colorectal cancer (CRC), comparing those who received chemotherapy to those who did not require chemotherapy, 73 with metastatic disease, and a group of 72 healthy controls.?The localized CRC patients were assessed at baseline (soon after diagnosis and prior to any chemotherapy), 6, 12 and 24 months.  The healthy controls and metastatic group were assessed at baseline, 6 and 12 months.  We also examined underlying mechanisms. (more…)
Author Interviews, Colon Cancer, Genetic Research, Journal Clinical Oncology / 03.11.2015

MedicalResearch.com Interview with: Hans F.A. Vasen, MD Department of Gastroenterology Leiden University Medical Center and Netherlands Foundation for the Detection of Hereditary Tumours Leiden, the Netherlands Medical Research: What is the background for this study? Dr. Vasen: People with familial colorectal cancer (CRC) have a 3-6 fold increased risk of colorectal cancer. It has been estimated that about 2% of the population have familial CRC (about 2.7 million people in the US). Previous studies showed that colonoscopic surveillance reduces the CRC-mortality by >80%. In people with hereditary CRC, i.e., Lynch syndrome (10 fold increased risk of CRC), an intensive screening program with colonoscopy 1x/1-2 years, is recommended. In familialcolorectal cancer, the optimal screening program  is unknown. Medical Research: What are the main findings? Dr. Vasen: In this randomized trial with 528 individuals at risk for familial CRC, we compared screening intervals of 3 and 6 years. We found that patients had significant more high-risk adenomas (precursor lesions of CRC) at 6-years-follow-up compared to at 3-years-follow-up. However, because of the relatively low rate of high-risk adenomas at 6 years (7%) and the absence of colorectal cancer in the 6-years group, we consider a 6-year-interval safe. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Cognitive Issues / 03.11.2015

MedicalResearch.com Interview with: Kelly N. H. Nudelman, Ph.D. Department of Radiology and Imaging Sciences Indiana University-Purdue University Indianapolis (IUPUI) Indianapolis, IN 46202 Medical Research: What is the background for this study? Dr. Nudelman: Varying levels of cognitive problems and related changes in brain structure and function have been reported in breast cancer patients treated with chemotherapy. Pain has also been associated with altered brain structure and function. However, the association of chemotherapy-induced peripheral neuropathy (CIPN), a side-effect of chemotherapy treatment characterized by nerve damage primarily in the extremities, has not been specifically investigated for association with cognitive symptoms in breast cancer. We used data from a prospective, longitudinal breast cancer cohort to investigate the relationship of CIPN and neuroimaging measures of cognitive dysfunction.  Medical Research: What are the main findings? Dr. Nudelman: We found that increased chemotherapy-induced peripheral neuropathy symptoms were associated with resting brain blood flow increase in regions known to be involved in pain processing. We also found that decreased frontal lobe gray matter density was correlated with these changes, suggesting a link between chemotherapy-induced peripheral neuropathy and cognitive dysfunction. (more…)
Author Interviews, Breast Cancer, Technology / 31.10.2015

MedicalResearch.com Interview with: Anuradha Godavarty PhD and Dr. Sarah J Erickson-Bhatt PhD Dept of Biomedical Engineering, Florida International University Miami, FL Medical Research: What is the background for this study? What are the main findings? Response: It is well known that early detection and staging of breast cancer is crucial in order to save lives. While the current gold standard for breast cancer screening is x-ray mammography, this method still misses many cancers especially in younger women with denser tissue. Our group and others have explored diffuse optical tomography using near-infrared light to image breast tumors. We have developed a unique optical imager with a hand-held probe that can contour to breast curvature in order to image the tissue without painful compression and without ionizing radiation (like x-rays). This study demonstrated the ability of the device to detect lesions in breast cancer patients due to elevated levels of total hemoglobin concentration in tumor vasculature. The hand-held has a potential to not only image the breast contours, but the probe was flexible to image the surrounding chest wall regions, thus expanding its application to image lymphatic spread as well. (more…)
Author Interviews, Cancer Research, End of Life Care, Nursing / 30.10.2015

Dr-Hsien-SeowMedicalResearch.com Interview with: Dr. Hsien Seow, PhD Associate Professor Department of Oncology Cancer Care Ontario Research Chair in Health Services Research Associate Member, Department of Clinical Epidemiology & Biostatistics McMaster University Canadian Institutes of Health Research Young Investigator Hamilton, Ontario Medical Research: What is the background for this study? What are the main findings? Dr. Seow: Despite being commonplace in healthcare systems, little research has described the effectiveness of publicly-provided generalist homecare nursing to reduce unnecessary acute care use at end-of-life, such as emergency department (ED) visits. It is also unclear how homecare nursing intent, which varies by standard care or end-of-life, affects this relationship. Our study examined a population-based cohort of cancer decedents in Ontario, Canada who used homecare nursing in their last six months of life. Specifically, we examined the relationship between homecare nursing rate in a given week on the ED visit rate in the subsequent week. In our cohort of 54,576 decedents, there was a temporal association between receiving end-of-life nursing in a given week during the last six months of life, and of more standard nursing in the last month of life, with a reduced ED rate in the subsequent week. Homecare nursing for those who are receving end of life care will find that it can provide immediate assistance when needed. (more…)
Author Interviews, Cancer, Cancer Research, JAMA / 29.10.2015

Jiemin Ma, PhD, MHS Director of Surveillance and Health Services Research American Cancer SocietyMedicalResearch.com Interview with: Jiemin Ma, PhD, MHS Director of Surveillance and Health Services Research American Cancer Society Medical Research: What is the background for this study? What are the main findings? Dr. Ma: This study is an analysis of long-term trends in mortality for all causes combined and for 6 leading causes of death, including heart disease, cancer, stroke, chronic obstructive pulmonary disease (COPD), unintentional injuries, and diabetes, in the United States from 1969 through 2013. We found that death rates for all causes and for five of these 6 leading causes (except COPD) decreased during this time period, although the rate of decrease appears to have slowed for heart disease, stroke, and diabetes. COPD death rates doubled during this time period, although the rate began to decrease in men since 1999. (more…)