AACR, Author Interviews, Cancer Research / 18.04.2023

MedicalResearch.com Interview with: Matthew H. Taylor, MD Earle A. Chiles Research Institute Providence Cancer Institute Portland, OR MedicalResearch.com: What is the background for this study? What is the importance of ILT4 or LILRB2 in tumor growth?
  1. ILT4, also known as LILRB2, is expressed on myeloid cells, including monocytes, DCs, macrophages and neutrophils. LILRB2 expressing myeloid cells promote tumor immune evasion and contribute to anti-PD1 resistance, making this a promising target to reverse myeloid-mediated immune suppression in the TME.
  2. IO-108 is a fully human IgG4 therapeutic antibody that binds to LILRB2 with high affinity and specificity, and blocks binding of LILRB2 to multiple cancer-relevant ligands. This blockade causes re-programming of immune suppressive myeloid cells to pro-inflammatory in the tumor microenvironment leading to the activation of T cells.
  3. This first-in-human, open-label Phase 1 study of IO-108 as monotherapy or in combination with pembrolizumab was designed to learn about safety, tolerability and preliminary efficacy of IO-108 as monotherapy or in combination with a PD-1 inhibitor in patients with advanced, metastatic solid tumors. The study was also designed to find a dose of IO-108 that is safe and efficacious to be tested in patients with various solid tumors.
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AACR, Author Interviews, Brigham & Women's - Harvard, Cancer Research / 18.04.2022

MedicalResearch.com Interview with: Ajit Johnson Nirmal PhD Instructor of Medicine, DFCI, HMS Laboratory of systems pharmacology Harvard Medical School MedicalResearch.com:  What is the background for this study?  Response: Like many other types of cancers, melanoma arises from gene mutations within cells that impact cell growth and division. These abnormal cells should be rapidly eliminated by our immune system, however, the failure to do so leads to the development of cancer. Hence researchers have long been interested to study the tumor environment that nurtures and sustains these dangerous cells. In the past, researchers have used single-cell technologies to delineate the cell types and cell states that make up the tumor microenvironment. However, the spatial relationships between these cell types and how they organize themselves such as to provide a favorable environment for the tumor to develop remains unknown. In the last couple of years, researchers have developed a new suite of new technologies called spatial omics which includes CYCIF a method that was developed at Sorger lab. Using this method, we can not only measure the molecular information of cells at a single cell level but also their spatial context. This allows us to build a google map like view of the skin with melanoma and study what is exactly happening that allows the tumors to develop. (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, NIH / 23.04.2021

MedicalResearch.com Interview with: Nishanth Ulhas Nair, Ph.D. Affiliation: Staff Scientist at Cancer Data Science Laboratory, Center for Cancer Research National Cancer Institute (NCI), National Institutes of Health (NIH) Bethesda, Maryland, USA. Date: April 22, 2021 Dr. Raffit Hassan and Dr. Eytan Ruppin at the National Cancer Institute (NCI) are the senior authors of this study.  MedicalResearch.com: What is the background for this study? Response: Malignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. An in-depth knowledge of genetic, transcriptomic and immunogenic events involved in mesothelioma is critical for successful development of prognostics and therapeutic modalities. In this study we aim to address this by exploring a new large scale patient tumor dataset of 122 mesothelioma patients, called NCI mesothelioma patient data, along with their genomic, transcriptomic, and phenotypic information. Unlike previous large-scale studies which have been focused on malignant pleural mesothelioma patients, our dataset contains an approximately equal representation of malignant pleural and peritoneal mesothelioma patients which allows to identify any differences between them. (more…)
AACR, Author Interviews, Cancer Research, MD Anderson / 12.04.2021

MedicalResearch.com Interview with: Vivek Subbiah, MD Department of Investigational Cancer Therapeutics Division of Cancer Medicine The University of Texas MD Anderson Cancer Center MedicalResearch.com: What is the background for this study? Response: RET fusions occur predominantly in 2% of lung cancers and 10-20% of thyroid cancers, and in low frequency in an increasing number of diverse cancers, including pancreatic cancer, salivary gland cancer, and colorectal cancer. The therapeutic relevance of RET fusions occurring outside of lung and thyroid cancers has not been well established.. (more…)
AACR, Baylor College of Medicine Houston, Cancer Research, Genetic Research, Prostate Cancer, Race/Ethnic Diversity, Social Issues / 10.04.2021

MedicalResearch.com Interview with: Nicholas Mitsiades MD Associate Professor of Medicine - Hematology and Oncology Baylor College of Medicine Oncologist at the Dan L Duncan Comprehensive Cancer Center  MedicalResearch.com: What is the background for this study? Response: African American men have higher risk of developing prostate cancer and up to 2.2-times higher mortality rate from prostate cancer relative to men of other ancestries. This is the largest health disparity across all cancers in the US. Socioeconomic factors, especially access to healthcare, definitely contribute to this disparity. African American men are diagnosed with prostate cancer at a more advanced stage than other races, and this is unfortunately very common at Ben Taub Hospital, our safety-net hospital in the Houston area, where we serve large racial and ethnic minority populations and patients who lack commercial insurance. (more…)
AACR, Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Pediatrics / 10.04.2021

MedicalResearch.com Interview with: Gregory K. Friedman, MD Associate Professor Director, Developmental Therapeutics Associate Scientist, O'Neal Comprehensive Cancer Center at UAB Neuro-Oncology Program Division of Pediatric Hematology-Oncology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? Response: This was a first-in-children trial to test the safety of an immunotherapy using an altered cold-sore virus (herpes virus or HSV-1), G207, infused directly via catheters into progressive or recurrent malignant brain tumors. Due to modifications in G207, the virus does not harm normal cells but can infect and directly kill tumor cells while also stimulating the patient’s own immune system to attack the tumor. We tested G207 at two dose levels alone and when combined with a single low dose of radiation, which was used to increase virus replication and spread throughout the tumor. The research is important because outcomes are very poor for children with progressive malignant brain tumors, and the toxicities caused by current standard therapies are unacceptably high. Therefore, we greatly need effective and less-toxic targeted therapies for children. (more…)
AACR, Author Interviews, Brigham & Women's - Harvard, Cancer Research, Nutrition, Prostate Cancer / 10.04.2021

MedicalResearch.com Interview with: Dr. Anna Plym PhD Postdoctoral Research Fellow Brigham and Women's Hospital Harvard T.H. Chan School of Public Health  MedicalResearch.com: What is the background for this study? What are the main elements of the healthy lifestyle? Response: Prostate cancer is the most heritable of all cancers, with genetic factors accounting for a large proportion of cases. Although we do not currently know about all the genetic factors contributing, a recent study identified 269 genetic markers for prostate cancer, validated in multiple independent populations (Conti et al., Nature Genetics 2021, Plym et al, JNCI, 2021: https://academic.oup.com/jnci/advance-article-abstract/doi/10.1093/jnci/djab058/6207974). Based on a polygenic risk score derived from these 269 markers, we observed that men with a high polygenic risk score have over a 50% risk of developing prostate cancer within their lifetime. With this excess risk in mind, we were interested in possible ways in which the genetic risk of prostate could be attenuated. An increasing number of studies have suggested that lifestyle factors can affect the risk of lethal prostate cancer – however, these studies have seldom incorporated genetic factors. We know from other diseases that a healthy lifestyle is of benefit for individuals at high genetic risk, and we hypothesized that this would be the case for prostate cancer as well. In this study, we examined a healthy lifestyle score for lethal prostate cancer consisting of six components: healthy weight (BMI < 30), not smoking (never smoked or quit > 10 years ago), vigorous physical exercise (3 or more hours per week), high intake of tomatoes or tomato-based products (7 servings or more per week), high intake of fatty fish (1 or more serving per week) and low intake of processed meat (less than 3 servings/week of beef or pork hot dogs, bacon, salami, bologna, or other processed meat sandwiches) (Kenfield et al, JCO, 2016).  (more…)
AACR, Author Interviews, Cancer Research / 16.07.2020

MedicalResearch.com Interview with: Radek Spisek MD PhD Charles University in Prague  MedicalResearch.com: What is the background for this study? Response: Immune cytokine IL-15 is a highly promising immuno-oncology target that mobilizes the two most important cell types driving anti-cancer immune responses: cytotoxic T cells and natural killer (NK) cells. Stimulating IL-15 receptors on these cells represents a potent and complementary mechanism to existing cancer treatments, such as PD-1 checkpoint inhibitors or monoclonal antibodies. Sotio is developing an IL-15 superagonist, SO-C101, as a potent immunotherapy for patients with cancer. This study examined SO-C101 in multiple tumor mouse models alone and in combination with PD-1 inhibition.  (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Colon Cancer / 26.06.2020

MedicalResearch.com Interview with: Guardant HealthVan Morris, M.D. Department of Gastrointestinal Medical Oncology Division of Cancer Medicine MD Anderson Center MedicalResearch.com: What is the background for this study? Response: Stage II colon cancer is diagnosed in approximately 25% of all colon cancer cases.  Oncologists do not have a reliable biomarker to identify patients who do or do benefit from adjuvant chemotherapy for this population of patients.  Circulating tumor DNA is shed by tumor cells as they die and harbors somatic mutations which distinguish its DNA from that of normal cells. Recently, circulating tumor DNA has shown great promise in distinguishing patients with colon cancer (as well as other solid tumors) that do or do not recur after surgery.  Here, patients who have detectable circulating tumor DNA - a surrogate for the presence of microscopic, minimal residual disease – inevitably recur, whereas the likelihood of recurrence is much lower for patients who do not have detectable ctDNA. (more…)
AACR, Author Interviews, Boehringer Ingelheim, Cancer Research / 13.05.2020

MedicalResearch.com Interview with: Dr. Udai Banerji, MD The Institute of Cancer Research and The Royal Marsden MedicalResearch.com: What is the background for this study? Response: Not only have I been working in the RAS mutations oncology world for a while, but I also have prior preclinical experience working with VS-6766 (RAF/MEK inhibitor) and defactinib (FAK inhibitor), the two drugs in the Phase 1 study that was presented at the American Association for Cancer Research (AACR) annual medical meeting on April 27th. It is important to know that there is a great significant medical need for novel treatments for KRAS mutant tumors, which are difficult to treat, aggressive, and quite common across advanced solid tumors, including low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), resulting in the need for novel treatments in an area of significant medical need. I felt that early signals in preclinical research warranted a clinical trial; so that, combined with my RAS experience, made pursuing the Phase 1 study a clear fit. A clinical trial setting allowed us to explore RAF and RAS inhibitor combinations in multiple tumor trials, which was our aim. The data presented at AACR convey safety and dose response results from the dose-escalation portion and expansion cohorts from an open-label, investigator-initiated Phase 1 study evaluating the combination of VS-6766 (RAF/MEK inhibitor) and defactinib (FAK inhibitor) therapy in patients with LGSOC and KRAS mutant NSCLC. The introductory data described in the study suggest that a novel intermittent dosing schedule of RAF/MEK and FAK inhibitor combination therapy has promising clinical activity in patients with KRAS mutant LGSOC and KRASG12V mutant NSCLC, including patients formerly treated with a MEK inhibitor. Expansion cohorts remain ongoing.  (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, MD Anderson, Pharmaceutical Companies / 09.05.2020

MedicalResearch.com Interview with: David S Hong, M.D MD Anderson Department of Investigational Cancer Therapeutics Division of Cancer Medicine University of Texas MedicalResearch.com: What is the background for this study? Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets. In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated robust tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%. In this analysis presented at AACR 2020, we sought to evaluate the outcomes in patients from the integrated data set based on different baseline characteristics, including prior lines of therapy and Eastern Cooperative Oncology Group (ECOG) performance status. ECOG measures how the disease impacts a patient. ECOG describes a patient’s level of functioning with a numbering scale (0-5) so physicians can uniformly describe a patient’s ability to care for themselves, daily activity and physical activity (selfcare, walking, working, etc). (more…)
AACR, Author Interviews, Bayer, Cancer Research / 08.05.2020

MedicalResearch.com Interview with: David S Hong, M.D Department of Investigational Cancer Therapeutics Division of Cancer Medicine MD Anderson, University of Texas MedicalResearch.com: What is the background for this study? Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets. In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%. A variety of NTRK genes have been identified in various tumor types including fusions and non-fusions (e.g., amplifications, rearrangements, deletions, slice variants). In the analysis presented at AACR 2020, we sought to evaluate this pooled data to determine the efficacy of larotrectinib in patients with non-fusion alterations in NTRK genes.  (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, Yale / 27.02.2020

MedicalResearch.com Interview with: Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director, Breast Cancer Translational Research Co-Director, Yale Cancer Center Genetics and Genomics Program Yale Cancer Center Yale School of Medicine New Haven, CT 05620  MedicalResearch.com: What is the background for this study? Response: We analyzed breast cancer tissues obtained before any therapy and the same cancers after 20 weeks of chemotherapy. This setting is ideal to find out what genomic changes have occurred in cancers that survived therapy. Due to the paucity of such specimens few other studies exist in this space. (more…)
AACR, Author Interviews, Cancer Research, Ovarian Cancer / 23.12.2019

MedicalResearch.com Interview with: Rugang Zhang, Ph.D Professor & Co-Leader, Gene Expression & Regulation Program Deputy Director, The Wistar Institute Cancer Center MedicalResearch.com: What is the background for this study? Response: Although the majority of epithelial ovarian cancer (EOC) patients initially respond well to platinum therapy, relapse ultimately occurs, which remains a major challenge in the clinical management of EOC. Substantial evidence suggests that cancer stem-like cells (CSC) contribute to chemotherapy resistance and elimination of CSC prevents the therapeutic relapse including in EOCs. Thus, therapeutic elimination of EOC CSCs represents a promising approach to achieve a durable therapeutic outcome by preventing chemotherapy resistance. Platinum-based chemotherapies are known to induce senescence that limits the propagation of cells subjected to insults such as cancer chemotherapeutics. In contrast to apoptosis, senescent cells remain viable. Senescent cells secrete a plethora of pro-inflammatory cytokines and chemokines, which is termed senescence-associated secretory phenotype (SASP). Therapy-induced inflammation promotes tumor progression and therapy resistance, and the SASP is known to promote cancer stem-like cells. However, clinically applicable approaches to target stemness associated with therapy-induced senescence remain to be explored.  (more…)
AACR, Author Interviews, Cancer Research / 19.12.2019

MedicalResearch.com Interview with: Dr. Samir Parekh, MBBS Associate Professor Medicine, Hematology and Medical Oncology Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Would you briefly describe what is meant by 'neoantigens'? How might they be used to stimulate immunity in a multiple myeloma patients?  Response: Myeloma is considered a “cold” tumor for immunotherapy (as compared to some solid tumors such as melanoma) given the relatively fewer DNA mutations in an average myeloma patient. Our clinical experience suggests that this may not be totally correct.  Our findings focus on mutations that can become antigens (neo-antigens) and challenges the stereotype. We can create vaccines based on peptides resulting from these mutations to stimulate immune responses. (more…)
AACR, Author Interviews, Melanoma / 20.10.2019

MedicalResearch.com Interview with: Qing Chen, M.D., Ph.D. Assistant Professor, Immunology, Microenvironment & Metastasis Program Scientific Director, Imaging Facility The Wistar Institute MedicalResearch.com: What is the background for this study? Response: We are focusing on how a specific type of brain cells, astrocytes, helps the cancer cells from melanoma and breast cancer to form metastatic lesions.  (more…)
AACR, Author Interviews, Pancreatic / 24.09.2019

MedicalResearch.com Interview with: Hadas Reuveni, PhD VP of Research and Development Kitov Pharma MedicalResearch.com: What is the background for this study? Response: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide. Current treatments fail to provide patients with an effective and long-lasting response, mostly given to the nature of the tumor microenvironment which hinders drug accessibility, the late stage on diagnosis and the rapid upregulation of compensatory alternative signaling pathways by the tumor cells that lead to cancer drug resistance. Two of the major parallel pathways regulating tumor survival and metastasis as well as the crosstalk of the tumor and its microenvironment are mediated by insulin receptor substrate (IRS) 1 and 2, and by the signal transducer and activator of transcription 3 (STAT3). Both IRS1 and STAT3 have been shown to play a significant role in development of drug resistance by tumor cells. NT219, the focus of the current study, is a small molecule that presents a new concept in cancer therapy. NT219 represents a new family of novel compounds acting as a dual inhibitor of both IRS1/2 and STAT3 signaling both directly in the tumor and its microenvironment. We have previously shown that simultaneous inhibition of these two pathways is crucial to overcome drug resistance, and to prolong the positive response of the anti-cancer activity of approved cancer drugs. NT219 targets IRS1/2 for degradation using a unique mechanism, supported by a feed-forward decrease in IRS gene expression. A long-term suppression of both IRS and STAT3 by NT-219 has been demonstrated in previous preclinical studies, which lasted days following removal of NT219 from the cancer cells, assuring a strong and prolonged anti-cancer activity. This study was designed to investigate the efficacy of NT219 at overcoming drug resistance to several approved oncology therapies using patient-derived xenograft (PDX) models of KRAS mutant pancreatic cancer, as well as to validate NT219's mechanism of action and optimal dose regimen.  (more…)
AACR, Author Interviews, CT Scanning, Lung Cancer / 28.06.2019

MedicalResearch.com Interview with: Barbara Nemesure, PhD Professor, Department of Family, Population and Preventive Medicine Division Head, Epidemiology and Biostatistics Director, Cancer Prevention and Control Program Director, Lung Cancer Program, Stony Brook Cancer Center Renaissance School of Medicine Stony Brook University    MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lung cancer is the most common cause of cancer death, claiming the lives of more than 150,000 people in the United States each year. While lung nodules are not uncommon, it has remained a challenge to differentiate those that will progress to cancer and those that will remain benign. Although numerous risk prediction models for lung cancer have been developed over the past 2 decades, the majority have been based on retrospective analyses or high risk groups with a strong history of tobacco use. To date, there have been a limited number of large-scale, prospective studies evaluating risk that a nodule will convert to cancer in the general population. This investigation aimed to construct a population-based risk prediction model of incident lung cancer for patients found to have a lung nodule on initial CT scan. The derived model was determined to have high accuracy for predicting nodule progression to cancer and identified a combination of clinical and radiologic predictors including age, smoking history (pack-years), a personal history of cancer, the presence of chronic obstructive pulmonary disease (COPD), and nodule features such as size, presence of spiculation and ground glass opacity type. When compared to patients in the low risk category, those defined as high risk had more than 14 times the risk of developing lung cancer. Quantification of reliable risk scores has high clinical utility, enabling physicians to better stratify treatment plans for their patients.      (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Surgical Research / 08.04.2019

MedicalResearch.com Interview with: Sharon S. Lum, MD, FACS, Professor Department of Surgery-Division of Surgical Oncology Medical Director of the Breast Health Center Loma Linda University Health Loma Linda University School of Medicine  MedicalResearch.com: What is the background for this study?   Response: Anecdotally, we observed that many patients with advanced HER2+ breast cancer have had tremendous responses to the new targeted therapies and the oncologists were referring them back to surgeons for consideration of local regional therapy. While traditionally surgeons have avoided operating on metastatic breast cancer patients due to the patient’s likelihood of dying from their metastatic disease, these HER2+ patients seemed to be doing so well that surgery might make sense. In our surgical oncology clinic, we seemed to be operating more on these patients. Since these patients seemed to be living longer, they might survive long enough for their primary tumor to become a problem for them. However, we did not have any data to support doing surgery in these cases. Prior studies have demonstrated mixed results regarding the survival benefit from surgery for stage IV breast cancer patients, but these were completed prior to routine use of anti-HER targeted therapies, so we wanted to further examine the role of surgery in HER2+ stage IV breast cancer patients. (more…)
AACR, Author Interviews, Cancer Research, HPV, University of Michigan, Vaccine Studies / 05.04.2019

MedicalResearch.com Interview with: Diane Harper, M.D., M.P.H., M.S. Professor of Family Medicine and Obstetrics and Gynecology Senior Associate Director, Michigan Institute for Clinical and Health Research Physician Director for Community Outreach, Engagement and Health Disparities, Rogel Cancer Center Michigan Medicine  MedicalResearch.com: What is the background for this study? Response: There is no current cure for women with HPV infection that has progressed to CIN 2/3 disease. The only treatment is for the diseased cervix, and does not eliminate the risk of another CIN 2/3 from the HPV infection 15-20 years later. This vaccine is made from a live virus that has 3 genes inserted:  human cytokine IL-2, and modified forms of HPV 16 E6 and E7 proteins. When the vaccine is injected subcutaneously, the proteins for HPV 16/E6 and E7 and the cytokine LI-2 proteins are made. These proteins trigger the immune response.  This is very different form imiquimod which is topical and not specific for HPV. (more…)
AACR, Author Interviews, Cancer Research, Dental Research, Pancreatic, Race/Ethnic Diversity / 28.03.2019

MedicalResearch.com Interview with: Julie R. Palmer, ScD Professor, Boston University School of Medicine Associate Director, Slone Epidemiology Center at Boston University Boston, MA 02118  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since 1995, 59,000 African American women from all regions of the U.S. have participated in a Boston University research study of the health of Black women.  Study participants complete mailed or online questionnaires every two years. Our major goal is to identify modifiable risk factors for cancers and nonmalignant conditions that disproportionately affect African Americans (e.g., pancreatic cancer, early-onset breast cancer, type 2 diabetes, uterine fibroids).  The reasons for the higher incidence of pancreatic cancer in African Americans relative to non-Hispanic White women in the U.S. are unknown. I was aware that several recent studies in predominantly White populations had observed a higher incidence of pancreatic cancer in those who had reported poor oral health and wondered whether the higher prevalence of poor oral health among African Americans could play a role in their higher incidence of pancreatic cancer.  We had already asked about gum disease, periodontal disease, and adult tooth loss in several rounds of data collection. After rigorous analysis, we found that women who reported any adult tooth loss had about two times the risk of future development of pancreatic cancer compared with those who had no tooth loss and had never reported periodontal disease. The estimated risk was even greater for those who had lost five or more teeth. A similar association was observed for reports of periodontal disease, but the association was not statistically significant. (more…)
AACR, Author Interviews, Biomarkers, MD Anderson / 05.03.2019

MedicalResearch.com Interview with: Vassiliki Papadimitrakopoulou, MD Professor of Medicine Department of Thoracic/Head and Neck Medical Oncology MD Anderson Cancer Center in Houston MedicalResearch.com: What is the background for this study? What are the main findings? Response: 30% of patients with newly diagnosed advanced NSCLC can be treated successfully with targeted therapies, often yielding higher response rates than chemotherapy or immune checkpoint inhibitors. Selecting first-line therapy for patients with NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET amplification and exon 14 skipping, and ERBB2, with NTRK newly added) Standard-of-care (SOC) testing relies on tissue, which is limited by biopsy-related risks, specimen insufficiency, and lab processing duration, which hamper timely optimal treatment selection -          NILE is a large, prospective, multicenter, head-to-head study of SOC tissue-based genomic testing to plasma-based comprehensive cfDNA genomic testing (Guardant360®). For the four biomarkers with FDA approved therapies, up to 34% of patients were tested by SOC tissue testing versus 95% with cfDNA testing. NILE met its primary endpoint - cfDNA performed similar to tissue in the detection of guideline-recommended biomarkers and cfDNA results were delivered significantly faster than SOC tissue testing (median 9 days vs. 15 days).Using cfDNA testing first, 87% of patients with a guideline-recommended biomarker would have been detected, compared to 67% if SOC tissue testing was first. (more…)
AACR, Author Interviews, Colon Cancer / 04.03.2019

MedicalResearch.com Interview with: Ronit Yarden, PhD, MHSA Director of Medical Affairs Colorectal Cancer Alliance, a patient advocacy organization Washington, D.C.  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The colorectal Cancer Alliance is a patient advocacy group (the largest advocacy group for colorectal cancer) and its mission is to provide support to patients, survivors, their caregivers and family members as well as advocate on their behalf for.  The organization is also committed to raise awareness for screening and early detection of colorectal cancer to help save lives and to provide funding for innovative colorectal cancer research. As part of our support we sought to identify some of the clinical, emotional and financial experiences and unmet needs of patients under 50 years old.  We conducted an online survey that was promoted through social media and 1195 patients and survivors completed our survey.  (more…)
AACR, Author Interviews, Cancer Research, MD Anderson, University Texas / 01.10.2018

MedicalResearch.com Interview with: Filip Janku, MD, PhD Associate Professor, Investigational Cancer Therapeutics (Phase I Clinical Trials Program) Center Medical Director, Clinical and Translational Research Center The University of Texas MD Anderson Cancer Center Houston, TX 77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clostridium novyi-NT is an attenuated strain of bacteria Clostridium, which induced a microscopically precise, tumor-localized response in a rat brain tumor model and in companion dogs bearing spontaneous cancers. Clostridium novyi-NT can only grow in hypoxic (low-oxygen) tumor environment and destroys cancer cells by secreting lipases, proteases, and other hydrolytic enzymes; recruiting inflammatory cells to tumors eliciting anti-tumor immune responses in animals. Furthermore, intratumoral injection can plausibly induce an immune mediated abscopal effect in non-injected tumor sites. Therefore, we designed a phase I dose-finding study to test for safety and tolerability of the single intratumoral injection of Clostridium novyi-NT in 24 patients with advanced cancers with no available standard therapies. We also designed experiments to study activation of antitumor immune response in blood and tumor samples from patients undergoing the therapy. We demonstrated that single dose of intratumoral injection of Clostridium novyi-NT is feasible and has led to significant destruction of injected tumor masses. Adverse events, which were often related to the tumor destruction at the infected site, could have been significant but mostly manageable. Correlative studies of pre-treatment and post-treatment tumor and blood samples suggested immune response to therapy. (more…)
AACR, Author Interviews, Biomarkers, Colon Cancer / 05.09.2018

MedicalResearch.com Interview with: Dr. Andrea Sottoriva, PhD Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by a liquid biopsy? Response: Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug. We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse. (more…)
AACR, Author Interviews, Cancer Research, Imperial College, Kidney Disease / 20.08.2018

MedicalResearch.com Interview with: Dr. David C. Muller PhD Faculty of Medicine, School of Public Health Research Fellow in Epidemiology and Biostatistics Imperial College, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our colleagues in the U.S. have been working on KIM-1 for years, particularly in the context of chronic kidney disease. Recently they found that KIM-1 is also elevated at the time of diagnosis of kidney cancer. We wanted to see if KIM-1 concentrations could predict the chances of a future diagnosis of kidney cancer. We found that KIM-1 was a strong predictor of being diagnosis with kidney cancer in the next 5 years. We also found that higher pre-diagnostic KIM-1 was associated with worse survival after diagnosis.  (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Lung Cancer / 01.08.2018

MedicalResearch.com Interview with: “smoking” by shira gal is licensed under CC BY 2.0Dr. Jose M. Martín-Sánchez IP of this study Grupo de Evaluación de Determinantes de Salud y Políticas Sanitarias Universitat Internacional de Catalunya Sant Cugat del Vallès Spain MedicalResearch.com: What is the background for this study? Response: Breast cancer has been the first cause of death from cancer among women. However, the mortality rates of breast cancer have been decreased in the last years. This downward trend can be attributed to treatment and screening programs. On the other hand, smoking has been increased among women during the last century and the main cause of lung cancer is smoking behavior. Based on this data, we hypothesized that the lung cancer mortality could outweigh the breast cancer mortality in the next years and the main purpose of this study was to project the mortality rates of lung cancer and breast cancer in women worldwide, based in previous data and using Bayesian methods, in order to identify potential strategies of public health to reduce the impact of lung cancer. Moreover, previous works described the lung and breast cancer mortality or projected one of them in a single country. For example, we have published two articles with data of Spain one of them with the description of lung cancer mortality trend in men and women and other with the projection of lung and breast cancer among women. The information of this study provides an overall point view around the word of this problem of public health. (more…)
AACR, Author Interviews, Cancer Research, Pancreatic / 02.07.2018

MedicalResearch.com Interview with: Michael J. Pishvaian, MD, PhD Phase I Program Director Assistant Professor Lombardi Comprehensive Cancer Center Washington, DC 20007 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Pancreatic cancer is a deadly disease and will soon be the second leading cause of cancer-related death. We have made some progress in the last few years....but despite this, patients with advanced, inoperable pancreatic cancer (which represents about 80% of pancreatic cancer patients) still only live 12 months, on average. We desperately need new therapies, AND to think "outside the box" for the treatment of pancreatic cancer. In that context, we have been learning that there are subgroups of patients with cancer whose tumors are particularly susceptible to certain therapies - either new therapies, or in some cases, approved therapies that would have not normally been used for that disease.  These specific patient subgroups with "actionable" findings have been identified through extensive genetic and molecular characterization of a patient's tumor. In the past there was a cynical perspective that pancreatic cancer did not harbor any "actionable" molecular abnormalities. We have now demonstrated that: 1) There are clearly and undeniably patients with pancreatic cancer whose tumors do indeed harbor "actionable" findings.  This represents at least 27% of pancreatic cancer patients, but may represent up to 50% as new therapies evolve.  These percentages are also highly consistent with similar publications in the pancreatic cancer field over the last few years; and 2) Importantly, we have been following our patients longitudinally for outcomes, and while it is still early, there is a statistically significant improvement in progression-free survival when a patient with a specific actionable molecular abnormality is treated with the appropriately "targeted" therapy.  This finding is also consistent with findings that have been observed in other cancer types.   (more…)
AACR, Aging, Author Interviews, Cancer Research, Immunotherapy, Melanoma / 21.06.2018

MedicalResearch.com Interview with: Ashani Weeraratna, Ph.D. The Ira Brind professor and Co-program leader of the Immunology, Microenvironment and Metastasis Program The Wistar Institute Member of Wistar’s Melanoma Research Center Philadelphia  MedicalResearch.com: What is the background for this study? What are the main findings?  Response:  This study shows for the first time that older patients, especially those who have had prior MAPKi therapy fare better than younger patients when treated with anti-PD1. We found that tumors in younger patients and younger mice have higher levels of Tregulatory cells, the cells that regulate other immune cells. This is not true systemically, only within the tumor microenvironment. We were surprised because we expected that, as with targeted therapy, older patients would have a poorer response to immunotherapy, given what we perceive as a poorer immune system in older patients.  (more…)
AACR, Author Interviews, Genetic Research / 18.04.2018

MedicalResearch.com Interview with: Ed Liu, M.D President and CEO The Jackson Laboratory (JAX) MedicalResearch.com: What is the background for this study? What are the main findings? Response: A few years ago we and others identified a complex genomic instability profile commonly found in the genomes of breast, ovarian and endometrial carcinomas, which is characterized by hundreds of isolated head-to-tail duplications of DNA segments, called tandem duplications. We refer to this configuration as the tandem duplicator phenotype, or TDP. In this study, we perform a meta-analysis of over 2,700 cancer genomes from over 30 different tumor types and provide a detailed description of six different types of TDP, distinguished by the presence of tandem duplications of different sizes. Collectively, these profiles are found in ~50% of breast, ovarian and endometrial carcinomas as well as 10-30% of adrenocortical, esophageal, stomach and lung adeno-carcinomas. We show that distinct genetic abnormalities associate with the distinct TDPs, clearly suggesting that distinct molecular mechanisms are driving TDP formation. In particular, we provide strong evidence of a casual relationship between joint abrogation of the BRCA1 and TP53 tumor suppressor genes and the emergence of a short-span (~11 Kb) TDP profile. We also observe a significant association between hyper-activation of the CCNE1 pathway and TDP with medium-span (~230 Kb) tandem duplications, and between mutation of the CDK12 gene and medium- and large-span TDP (coexisting 230 Kb and 1.7 Kb tandem duplications). Importantly, we find that different forms of TDP result in the perturbation of alternative sets of cancer genes, with short-span TDP profiles leading to the loss of tumor suppressor genes via double transections, and larger-span TDP profiles resulting in the duplication (i.e. copy number gain) of oncogenes and gene regulatory elements, such as super-enhancers and disease-associated SNPs.  (more…)