Cancer Research / 01.03.2021

liver-metastases-cancer-chemoebolization.jpegOne of the main dangers of cancer is metastasizing. This process can affect any organ in the human body. The most frequent causes of liver metastases are tumors of the gastrointestinal tract, mammary glands, lungs, and pancreas. One of the modern methods of liver metastases treatment today is chemoembolization procedure. Its use allows doctors to fight cancer liver metastases with minimal harm to the patient. Statistics shows that this method is 30% more effective than traditional treatment of metastases with systemic chemotherapy. Symptoms As a rule, secondary liver cancer has no symptoms for a long time. This makes it difficult to diagnose this type of oncology. However, with regular medical check-ups, you can avoid this. To know when you should see a doctor, you need to know the symptoms of liver metastases that are most commonly seen:
  • Abdominal bloating
  • Nausea and vomiting
  • Constipation or diarrhea
  • Decreased appetite
  • Severe weight loss
  • Persistent low-grade increase in body temperature
  • General weakness and fatigue
If you have one or more of these symptoms, it is better to see your doctor. This will allow the tumor to be diagnosed at an early stage, so you can improve your prognosis for treatment and also make it less harmful to your health. (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research / 05.06.2018 Interview with: Dr. Giuseppe Del Priore, MD, MPH Chief Medical Officer of Tyme Inc. What is the background for this study? What are the main findings? Response: Metastatic breast cancer, sometimes also called “stage IV” or “advanced breast cancer,” is the most extensive stage of breast cancer. It is an invasive cancer that has spread to other parts of the body, most often bones, lungs, liver, and brain. The current standard of care for metastatic breast cancer is systemic drug therapies, such as hormone therapy, chemotherapy, targeted drugs or a combination of these.  Because they reach every cell in the body, they have side effects that can worsen the patient’s quality of life. Existing treatments cannot cure metastatic breast cancer and are palliative in intent. This presents a great unmet need and challenge in treating patients with metastatic breast cancer. SM-88 is a novel relatively non-toxic combination therapy that harnesses cancer’s unique cell metabolism and oxidative stress to selectively drive cancer cell death. Earlier studies with SM-88 therapy demonstrated its potential efficacy in breast and other metastatic cancers. In this current report, we assessed the efficacy of SM-88 in patients with metastatic breast cancer from the first in human “Phase 1” and compassionate use programs from 2012 to 2017. Data demonstrated the potential efficacy of SM-88 in metastatic breast cancer with favorable safety and quality of life profiles. In addition, there were no indications of cross-resistance based on hormone profile, previous treatments or metastatic site. This is an extremely important finding since most cancer deaths are due to resistance to subsequent therapies.  As predicted by the SM-88 mechanism of action, we could not detect this problem with SM-88 use. (more…)
ASCO, Author Interviews, Cancer Research, Journal Clinical Oncology, Kidney Disease, UT Southwestern / 01.01.2018 Interview with: Kevin D. Courtney, M.D., Ph.D.  Assistant Professor UT Southwestern Medical Center What is the background for this study? What are the main findings? Response: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Metastatic ccRCC does not respond to traditional chemotherapy. Current standard treatments for metastatic ccRCC include drugs called vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) that block the growth of new blood vessels that feed the cancer, as well as drugs that inhibit an enzyme called mTOR that is involved in ccRCC growth and immune therapies that rev up the body’s immune response to try to fight the cancer. Each of these treatments can have significant side effects for patients that can make them difficult to tolerate. Metastatic ccRCC is largely incurable, and we need novel and better-tolerated treatments. A central driver of ccRCC is a protein called hypoxia inducible factor 2alpha (HIF-2alpha). This protein has been very difficult to try to target with a drug. This study is the first to test a drug that targets HIF-2alpha in patients with metastatic ccRCC. The study results showed that the HIF-2alpha inhibitor, PT2385 (Peloton Therapeutics) was active in fighting metastatic ccRCC and was well-tolerated. (more…)
Author Interviews, Cancer Research, Orthopedics, Pharmacology / 13.11.2017 Interview with: Charles L.Shapiro MD Professor of Medicine Director of Translational Breast Cancer Research Director of Cancer Survivorship Division of Hematology/Oncology Tisch Cancer Institute New York, NY What is the background for this study? What are the main findings? Response: The new 2017 ASCO guidelines for the use bone-modifying in individuals with bone metastases recently endorsed every 3-month zoledronic, because of high level evidence from three randomized trials, including our trial (published in Jama in Jan 2017, first author Himelstein et al) that giving zoledronic acid every 3-months was non-inferior to the standard of monthly zoledronic. The guidelines also concluded that there was not one preferred bone modifying agent of the other, despite the fact the comparing monthly zoledronic to monthly denosumab in women with bone metastases, denosumab delayed the time to first skeletal-related event (pathological fractures, necessity for radiation or surgery, and spinal cord compression) and subsequent events by 23% (or in absolute terms about 3 months) . Zoledronic acid became generic in 2013, whereas monthly denosumab is still patented until 2022-25. (more…)
Author Interviews, Cancer Research, JAMA / 02.08.2017 Interview with: Benjamin Weixler, MD Department of Surgery University Hospital Basel, Basel, Switzerland and Leiden University Medical Center, Leiden, the Netherlands What is the background for this study? What are the main findings? Response: For most patients with lymph node negative colon cancer (stage I and II) surgery is regarded to be the curative treatment. Despite the curative attempt up to thirty percent of these patients will develop disease recurrence, most likely due to missed micro-metastatic disease at initial tumor staging. Pathological standard processing with hematoxylin and eosin (H&E) entails a considerable risk of missing micro-metastatic deposits in the lymph nodes. Mounting evidence indicates that micro-metastatic tumor deposits in the lymph nodes as well as in the bone marrow might be associated with an increased risk of disease recurrence and death in node negative patients. With our study we wanted to examine the correlation between the occurrence of micro-metastatic deposits in the lymph nodes and the bone marrow as well as their prognostic significance. As a main finding, the study provides compelling evidence that tumor cell dissemination to the lymph nodes and to the bone marrow are independent events in patients with colon cancer. Most importantly did the study demonstrate that micro-metastatic deposits in the lymph nodes as well as in the bone marrow are independent negative prognostic factors regarding  disease-free and overall survival. The combined occurrence is associated with significantly worse prognosis compared to either one of them. (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson, Orthopedics / 12.02.2017 Interview with: Gabriel N. Hortobagyi, MD, FACP, FASCO Professor, Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX 77230-1439 What is the background for this study? What are the main findings? Response: Bisphosphonates have been commercially available for several decades as supportive care for patients with bone metastases. They reduce the frequency and severity of bone-related complications. While the optimal dose and short-term scheduling of zoledronic acid (and previously, pamidronate) have been determined, there has been no research to determine how long these drugs need to be maintained nor the optimal dose and schedule beyond the first year of therapy. These questions are particularly important for this family of drugs, since they are incorporated into bone and not excreted from the body for many years. We set out to determine whether a reduction in the frequency of administration of zoledronic acid (every 12 weeks) was able to maintain the therapeutic efficacy of this intervention when compared to the “standard” schedule of administration (every 4 weeks). It was a prospective, randomized, non-inferiority trial that recruited patients with metastatic breast cancer with bone metastases and who had previously received 9 or more doses of zoledronic acid or pamidronate. The primary endpoint was the proportion of patients with one or more skeletal-related events. Four hundred and sixteen patients were randomized in a 1:1 ratio. The two groups were comparable at baseline. After the first year of follow-up, there was no statistically significant difference in SRE rate between the two arms, confirming the non-inferiority fo the every-12-week schedule of zoledronic acid. (more…)
Author Interviews, Cancer Research, JAMA, Orthopedics / 06.01.2017 Interview with: Charles L. Shapiro, MD Professor of Medicine Co-Director of Dubin Breast Center Director of Translational Breast Cancer Research Director of Cancer Survivorship, Tisch Cancer Institute Mount Sinai Health System Division of Hematology / Medical Oncology: Tisch Cancer Institute New York, NY 10029 What is the background for this study? What are the main findings? Response: Metastases to bone are frequent in many cancers and cause pain, pathological fractures, necessitate surgical and/or radiation treatments, cause spinal chord compression that can lead to paralysis, and significantly increase health care costs. Zoledronic acid, a bisphosphonate that inhibits bone resorption, is used in standard practice because it reduces the risks skeletal-related events including cancer-related pathological fractures, the need for surgery and/or radiation to bone metastases, and spinal chord compression in patients with breast cancer, prostate cancer and multiple myeloma. However, the optimal dosing interval for zoledronic acid is unknown and based on prior studies and empiricism it is administered monthly along with anti-cancer treatments. In this trial, over 1800 breast cancer, prostate cancer and multiple myeloma patients with bone metastases were randomized to the standard dosing interval of monthly zoledronic acid versus every 3-months zoledronic acid for a duration of two years. The results overall, and in each specific disease site, show that giving zoledronic acid once every 3-months as opposed to monthly did not result in any increase in skeletal-related events. (more…)
Author Interviews, Cancer Research, JAMA, Prostate Cancer / 03.01.2017 Interview with: Dr. Jim C. Hu MD MPH Professor of Urology Weill Cornell Medicine What is the background for this study? What are the main findings? Response: The most significant finding from our population based study is that after years of decline following the introduction of PSA screening, we see a rise in the incidence of metastatic prostate cancer at diagnosis among men aged 75 years and older. This is concerning in light of recent criticisms and guidelines against PSA testing. For instance, in 2008, the US Preventative Services Task Force recommended against PSA testing in this age group, and in our study, we see the incidence of metastasis at diagnosis rising in 2012 and 2013. This is significant because there is no cure for men with metastatic prostate cancer of their disease. The traditional argument against PSA screening is that it leads to over-diagnosis and over-treatment of prostate cancer. However, we currently do not have a better test for diagnosing prostate cancers before it has spread beyond the prostate and metastasized. Remarkably, when Ben Stiller shared his personal use of PSA testing in his mid to late 40's and how this led to a detection of intermediate risk prostate cancer that led him to surgery and cure, others criticized him for sharing his story. (more…)
Author Interviews, Biomarkers, Cancer Research, Prostate Cancer, Science / 27.09.2016 Interview with: Iryna Saranchova MD PhD candidate Michael Smith Laboratories Vancouver, BC What is the background for this study? • The immune system is efficient at identifying and halting the tumour emergence at early stages. However, when metastatic (sufficient to cause death) tumour appears, the immune system is no longer able to recognize the cancer cells and control their growth and spread. • Recent studies of solid cancers have shown considerable heterogeneity between different tumour types and several lines of evidence suggest that tumours are not only heterogeneous, but they constantly evolve during the disease progression and this often hampers the existing treatment methods. • It means that it is important to consider each patient’s mutational changes accumulated over time in antecedent primary, metastatic lesions and/or local recurrences. This approach will help to understand the mechanism of tumour development, create a background for specific treatment modality and prevent therapeutic failure with consequent systemic relapse of the disease • Therefore, in our project we were aiming to find possible immune markers of tumour transition from the primary stage to its metastatic form. For this purpose, we selected a special study model: two pairs of separate mouse tumour cell lines, where metastatic cells arose from the initial primary tumour. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Nature, Technology / 23.09.2016 Interview with: Natalie Artzi PhD principal research scientist MIT's Institute for Medical Engineering and Science and Assistant professor of medicine Brigham and Women's Hospital With co-authors: Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Noam Shomron What is the background for this study? What are the main findings? Response: Metastases are the primary cause for mortality in breast cancer, the most common cancer in women regardless of ethnicity. Recent studies show that germline sequence variants, such as single-nucleotide polymorphisms (SNPs) in miRNA-binding sites, can disrupt the downregulation by miRNAs, with a profound effect on gene expression levels and consequentially on the phenotype, including increased risk for cancer. In the current study, we aimed to determine the potential effect of SNPs within miRNA-binding sites on metastatic breast cancer progression and their potential use as suppression targets to prevent metastasis. Our collaborators at Tel-Aviv Universityin a research led by Dr. Noam Shomron found that the SNP, rs1071738, located in a target site for miR-96 and miR-182 on the 3’-UTR of the PALLD gene, encodes the Palladin actin-associated protein, which is a documented player in breast cancer motility. In vitro experiments revealed a functional downregulation of Palladin levels by miR-96 and miR-182, which subsequently reduces migration and invasion abilities of breast cancer cells. My lab then showed in an in vivo experiment that the use of nanoparticles embedded in a hydrogel scaffold as a miRNA delivery vehicle enables an efficient and specific delivery of miR-96/miR-182 directly to breast tumours, which results in marked reduction of breast cancer metastasis. We then proceeded to study the effect of combination therapy in which we will use a chemotherapy drug to shrink the primary tumor and the miRNAs to prevent metastasis. The intercalation of a chemotherapy drug, cisplatin, to the miR-conjugated nanoparticles further improved the effect, leading to significant reduction in both primary tumour growth and metastasis. Our study highlights the therapeutic potential of miRNAs, and specifically miR-96 and miR-182, and support the importance of Palladin regulation in breast cancer metastasis. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, JNCI / 30.06.2015

Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts Interview with: Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114 MedicalResearch: What is the background for this study? What are the main findings? Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting. We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical models of spontaneous lymphatic metastasis, however there were no mechanistic data to explain these observations. Here, we developed a novel chronic lymph node window model to facilitate new discoveries in the mechanisms of growth and spread of lymph node metastases. Our new data provide pre-clinical evidence along with supporting clinical evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in adjuvant setting, particularly those involving lymph node metastases. (more…)
Author Interviews, Nature / 18.03.2015 Interview with: Dr. Pak Kin Wong Ph.D. Aerospace& Mechanical Engineering Department Biomedical Engineering and Bio5 Institute The University of Arizona Medical Research: What is the background for this study? What are the main findings? Response: Collective cell migration is central to various (patho)physiological processes, such as tissue development, regeneration, and cancer metastasis. At the onset of the process, a subset of cells acquires distinct leader cell phenotypes in the initially homogeneous population and leads the migration. However, how leader cells are initiated among the initial homogeneous population and how leader cell density is regulated during collective migration remain unknown. In this study, we demonstrate the formation of leader cells is regulated dynamically by Dll4 signaling through Notch1 and cellular stress near the leading edge. Our finding provides a molecular basis for the stochastic emergence of leader cells, a process originally considered random. (more…)
Author Interviews, Baylor College of Medicine Houston, Breast Cancer / 10.02.2015

Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, Interview with: Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, Texas   Medical Research: What is the background for this study? What are the main findings? Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they  the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process. In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones. We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases. (more…)
Author Interviews, Biomarkers, Electronic Records, JNCI, Prostate Cancer / 14.03.2014

Primo N. Lara, Jr, MD, Professor of Medicine, University of California Davis School of Medicine Associate Director for Translational Research UC Davis Comprehensive Cancer Center Sacramento, CA Interview with: Primo N. Lara, Jr, MD, Professor of Medicine, University of California Davis School of Medicine Associate Director for Translational Research UC Davis Comprehensive Cancer Center Sacramento, CA 95817 What are the main findings of the study: Dr. Lara:  “We found that blood markers of bone turnover can be used to predict outcomes in men with advanced prostate cancer with spread to bone. We also found that a small proportion of men could be predicted to benefit from an investigational drug based on these same markers.” (more…)
Author Interviews, Lung Cancer, University of Pennsylvania / 20.08.2013

Sandra Ryeom, PhD, Assistant professor of Cancer Biology, Perelman School of Medicine, University of Pennsylvania Interview with: Sandra Ryeom, PhD, Assistant professor of Cancer Biology, Perelman School of Medicine, University of Pennsylvania What are the main findings of the study? Answer: We identified an important pathway (calcineurin-NFAT-Angiopoeitin2) in the vasculature of early metastatic lung lesions that is critical for promoting lung metastases. Were any of the findings unexpected? Answer: Since there is limited understanding of regulation of tumor angiogenesis at metastatic sites, identification of the calcineurin pathway and a newly identified target of calcineurin-NFAT signaling  was all unexpected. (more…)
Author Interviews, Cancer Research, Stanford / 30.05.2013 eInterview with Ronald Levy, M.D. Professor and Chief Division of Oncology Stanford University, 269 Campus Drive Stanford, California 94305, USA What are the main findings of the study? Dr. Levy: Injection of antibodies that deplete Treg cells directly into a tumor can evoke an immune response that cures  the animal of distant, untreated tumors. This effect eliminates cancer even in the brain. The dose of antibodies locally injected can be as low as 1/100 the dose used for systemic injection and therefore should avoid the usual autoimmune side effects of these antibodies. The antibodies used are directed against CTLA4 and OX40 antigens. (more…)
Author Interviews, Cancer Research, Genetic Research, Lung Cancer / 26.05.2013 Authors’ Interview: Sophie Rousseaux and Saadi Khochbin INSERM, U823; Université Joseph Fourier, Grenoble 1; Institut Albert Bonniot, Grenoble F-38700, France. What are the main findings of the study? Answer: We first discovered that all cancer cells lose the ability to maintain gene silencing and therefore activate genes that should normally remain silent. Although present in all cells, some genes are normally expressed (or “active”) only in one cell type. For example, normal lung cells do not express genes that are only active in germ cells (i. e., cells that will become spermatozoa), but lung cancerous cells activate some of these germ cells-specific genes. In this work we designed a specific approach to detect these aberrant gene expressions and found that they occur in all cancers of all origins. We then decided to exploit this phenomenon to help the detection of cancers and predict their evolution. For this purpose, we chose to focus on lung cancer to establish “a proof of principle”. We found that, among all the genes wrongly expressed in the tumour cells, the activation of 26 of them enabled us to identify the most aggressive lung cancers. Compared with the existing information currently available for doctors (i.e.; tumour size, its pathological subtype…), our approach brings much more precision in predicting the evolution of the tumours and the prognosis of the patients. (more…)