Columbia University Irving Medical Center (CUIMC) and NewYork-Presbyterian researchers have created patient-specific bladder cancer organoids that mimic many of the characteristics of actual tumors. The use of organoids, tiny 3-D spheres derived from a patient’s own tumor, may be useful in the future to guide treatment of patients.
The study was published today in the online edition of Cell.
In precision medicine, molecular profiling of an individual patient’s tumor is used to identify genetic mutations that drive that individual’s cancer. That knowledge may help physicians select the best drug to fight the cancer, but the analysis does not always predict how a patient will respond to specific therapies.
Bladder cancer is a frequent disease affecting approximately 1,900 persons in Denmark annually. A high number of these patients only have superficial tumors in the bladder when the disease is diagnosed. For many years, this patient group will be examined frequently and during this time many get new tumors; some cases develop aggressively making it necessary to remove the bladder or receive chemotherapy.
A research team from Aarhus University Hospital and Aarhus University headed by professor Torben Ørntoft and professor Lars Dyrskjøt has been in charge of a larger European research project mapping the molecular mechanisms of early stages of bladder cancer in 460 patients in Denmark, Sweden, The Netherlands, Germany, Spain and Serbia. The researchers found that tumors can be divided into three primary classes with very different molecular and disease-developing characteristics. These findings may be important in risk assessment and subsequent choice of treatment.
Scientists have found that heating the chemotherapy drug mitomycin-C prior to using it for treating bladder cancer may radically improve its efficacy. The findings, published in the International Journal of Hyperthermia, are the result of a four-and-a-half-year study by medics based at Comarcal Hospital, Monforte, Spain.
The ‘Recirculant hyperthermic IntraVEsical chemotherapy (HIVECä)’ treatment devised by the researchers involved heating a solution of mitomycin-C and diluted water to a target temperature of 43 °C prior to delivery into the bladder. The drugs were recirculated at 200 mL per minute at a stable pressure, and the temperature inside the bladder was maintained for 60 minutes.
40 patients took part in the study, split into two groups — one which received the HIVECä treatment prior to a resection of the bladder, and another which received HIVEC after resection of the bladder.
Noguchi explained that immunotherapy has emerged recently as a viable and attractive strategy for the treatment of advanced cancer. “In this study, we assessed whether a novel immunotherapeutic approach that we have devised, called personalized peptide vaccination, could improve outcomes for patients who have advanced bladder cancer that has progressed after platinum-based chemotherapy,” he continued. “This is a disease for which the prognosis is poor; median survival is just 13 to 15 months from the time of starting platinum-based chemotherapy.”
Noguchi and colleagues enrolled 80 patients with bladder cancer that had progressed after platinum-based chemotherapy in the phase II clinical trial. Thirty-nine patients were randomly assigned to personalized peptide vaccine and best-supportive care and 41 to best-supportive care. Best-supportive care included palliative radiotherapy, antibiotics, and pain relief. Noguchi explained that personalized peptide vaccination involved patients receiving two to four peptides once a week for eight weeks and then once every two weeks for four doses. The peptides were selected from a pool of 31 peptides, and the identity of the peptides selected for each patient was determined by which form of a marker called human leukocyte antigen (HLA) class IA was expressed by the patient and whether there were signs of an existing immune response to the peptides in the patient’s blood.
Universitat Autònoma de Barcelona researchers have found a mycobacterium that is more effective in treating superficial bladder cancer and does not cause infections, unlike those used up to now.
Mycobacteria are the only bacteria used in cancer treatment. The administration of the bacterium Mycobacterium bovis (BCG), is the current treatment for superficial bladder cancer. It is inserted directly into the bladder through a catheter. BCG prevents new tumours from appearing, but despite its efficacy it has many adverse side effects, the most serious being BCG infections that need to be treated with antituberculous drugs.
A study on the characteristics of a wide group of mycobacteria begun seven years ago by the Mycobacteria Research Group, led by Dr Esther Julián, of the Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, has discovered that one of these, Mycobacterium brumae (M.brumae), is able to reduce the growth of tumour cells in the bladder and activate an immune response.
Scientists from Queen Mary University of London have made a breakthrough in developing a new therapy for advanced bladder cancer — for which there have been no major treatment advances in the past 30 years.
Published today in Nature, the study examined an antibody (MPDL3280A) which blocks a protein (PD-L1) thought to help cancer cells evade immune detection.
In a phase one, multi-centre international clinical trial, 68 patients with advanced bladder cancer (who had failed all other standard treatments such as chemotherapy) received MPDL3280A, a cancer immunotherapy medicine being developed by Roche. In addition, patients were all tested for the protein PD-L1 and around 30 were identified as having PD-L1 positive tumours.
New research which finds that invisible blood in urine may be an early warning sign of bladder cancer is likely to shape guidelines for clinicians.
Scientists at the University of Exeter Medical School found that one in 60 people over the age of 60 who had invisible blood in their urine (identified by their GP testing their urine) transpired to have bladder cancer. The figure was around half those who had visible blood in their urine — the best known indicator of bladder cancer. However, it was still higher than figures for other potential symptoms of bladder cancer that warrant further investigation.
Lead author Sarah Price, a PhD student at the University of Exeter Medical School, led the first robust study to investigate whether invisible blood in urine can indicate bladder cancer. Speaking as the study is published in the British Journal of General Practice on September 1 2014, she said: “It is well known that if you see blood in your urine you should contact your GP, who is likely to refer you for tests. But there is no clear guidance for GPs on what to do if they detect blood that is not visible during routine tests. We are hopeful that our findings will now lead to robust guidance that it warrants further investigation. Early diagnosis is crucial to have the best chance of successfully treating bladder cancer. The three-quarters of patients who are diagnosed early have much better outcomes than those whose disease is diagnosed late. Anything we can do to boost early detection is crucial to help save lives.”
A multi-center phase I study using an investigational drug for advanced bladder cancer patients who did not respond to other treatments has shown promising results in patients with certain tumor types, researchers report. Yale Cancer Center played a key role in the study, the results of which will be presented Saturday, May 31 at the 2014 annual conference of the American Society of Clinical Oncology (ASCO) in Chicago.
The trial included 68 people with previously treated advanced bladder cancer, including 30 patients identified as PD-L1 positive. PD-L1 is a protein expressed by many tumor types that can render the cancer invulnerable to immune attack. The patients in the study were treated with MPDL3280A, a drug being developed by Genentech, a member of the Roche group.
Researchers at Lund University have developed a classification system to determine the prognosis for bladder cancer. It is hoped that this will prove useful for future bladder cancer research and drug development.
“With this new classification system we can better predict which patients have a poor prognosis compared to current methods,” said Gottfrid Sjödahl, a doctoral student at the Division of Oncology, Lund University.
Bladder cancer is the fifth most common type of cancer in the Western world. The treatment offered to those with bladder cancer has not changed in the past 20 years. Many cancer researchers believe one of the reasons for this is the absence of a method to distinguish molecular differences in bladder cancer tumors.