Jun 14, 2017 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
New discoveries about the genetics of prostate cancer could lead to better tools for diagnosing the disease and selecting effective therapies based on each patient’s specific physiology
In recent decades, the biggest challenge for urologists, and for the pathologists who diagnosed the prostate tissue specimens they referred, has been how to accurately differentiate between non-aggressive prostate cancer, which can exist for decades with no apparent symptoms, and aggressive prostate cancer that kills quickly.
Thus, a research study that has identified unique genetic features within prostate cancer that can help determine if the cancer is aggressive or not, and whether certain drugs may be effective, is good news for men, for urologists, and for the clinical laboratories that will be called upon to perform testing.
These types of breakthroughs bring precision medicine ever closer to having viable tools for effective diagnosis of different types of cancer.
Genetic Fingerprints of Cancer Tumor Types
One such study into the genetic pathways of prostate cancer is bringing precision medicine ever-closer to the anatomic pathology laboratory. Researchers from the Princess Margaret Cancer Centre, which is associated with the University of Toronto Faculty of Medicine, have discovered that some tumors in prostate cancer have a genetic fingerprint that may indicate whether or not the disease will become more aggressive and less responsive to treatment.
Robert Bristow, MD, PhD, and Paul Boutros, PhD, conducted a study of nearly 500 Canadian men who had prostate cancer. Published in the journal Nature, the researchers examined the genetic sequences of those tumors, looking for differences between those that responded to surgery or radiation and those that did not.
In the video above, Dr. Robert Bristow, clinician-scientist at Princess Margaret Cancer Centre, discusses the findings of a key piece in the genetic puzzle that explains why men born with a BRCA2 mutation develop aggressive prostate cancer. (Caption and photo copyright: University Health Network/Princess Margaret Cancer Centre.)
According to a FierceBiotech article, approximately 30% of men who have a type of prostate cancer thought to be curable eventually develop an aggressive metastatic type of the disease. About half of the men who developed a metastatic form of cancer had mutations to three specific genes:
“This information gives us new precision about the treatment response of men with prostate cancer and important clues about how to better treat one set of men versus the other to improve cure rates overall,” stated Bristow in a University Health Network (UHN) press release.
In another study, researchers looked at 15 patients with BRCA2-inheritied prostate cancer and compared the genomic sequences of those tumors to a large group of sequences from tumors in less-aggressive cancer cases. According to a ScienceDaily news release, they found that only 2% of men with prostate cancer have the BRCA2-inherited type.
Knowing what type of cancer a man has could be critically important for clinicians tasked with prescribing the most efficient therapies.
“The pathways that we discovered to be abnormal in the localized BRCA2-associated cancers are usually only found in general population cancers when they become resistant to hormone therapy and spread through the body,” noted Bristow in the ScienceDaily release. If clinicians knew from diagnosis that the cancer is likely to become aggressive, they could choose a more appropriate therapy from the beginning of treatment.
Genetic Mutations Also Could Lead to Breast and Brain Cancer Treatments
BRCA mutations have also been implicated in breast, ovarian, and pancreatic cancers, among some other types. The knowledge that BRCA1 and BRACA2 mutations could indicate a more aggressive cancer is likely to spark investigation into whether poly ADP ribose polymerase (PARP) inhibitors could be used as an effective therapy.
PARP inhibitors are increasingly of interest to scientists. In addition to being used to treat some BRCA1/BRCA2-implicated cancers, two recent studies show that it could be effective in treating brain cancer with low-grade gliomas that involve a mutation to the gene isocitrate dehydrogenase (IDH), according to an article published by the National Cancer Institute and the National Institutes of Health (NIH).
Researchers of the study published in the journal Clinical Cancer Research investigated how PARP inhibitors impact DNA repair in gliomas.
Researchers of the study published in the journal Science Translational Medicine stated that they “demonstrate mutant IDH1-dependent PARP inhibitor sensitivity in a range of clinically relevant models, including primary patient-derived glioma cells in culture and genetically matched tumor xenografts in vivo.”
According to the UHN press release, the next step in using the knowledge that BRCA1 and BRCA2 may indicate a more aggressive prostate cancer is for researchers to create a diagnostic tool that can be used to determine what type of prostate cancer a man has. They expect the process to take several years. “This work really gives us a map to what is going on inside a prostate cancer cell, and will become the scaffold on which precision therapy will be built,” Boutros stated in a Prostate Cancer Canada news release.
Unlocking Knowledge That Leads to Accurate Diagnoses and Treatments
Research that furthers precision medicine and allows clinicians to choose the most appropriate treatment for individuals shows how quickly scientists are applying new discoveries. Every new understanding of metabolic pathways that leads to a new diagnostic tool gives clinicians and the patients they treat more information about the best therapies to select.
For the anatomic pathology profession, this shows how ongoing research into the genetic makeup of prostate cancer is unlocking knowledge about the genetic and metabolic pathways involved in this type of cancer. Not only does this help in diagnosis, but it can guide the selection of appropriate therapies.
On the wider picture, the research at the Princess Margaret Cancer Centre is one more example of how scientists are rapidly applying new knowledge about molecular and genetic processes in the human body to identify new ways to more accurately diagnose disease and select therapies.
—Dava Stewart
Related Information:
Genomic Hallmarks of Localized, Non-Indolent Prostate Cancer
Newly Discovered Genetic Fingerprint for Prostate Cancer Promises to Personalize Treatment
Prostate Cancer Team Cracks Genetic Code to Show Why Inherited Disease Can Turn Lethal
PARP Inhibitors May Be Effective in Brain, Other Caners with IDH Mutations
Chemosensitivity of IDH1-Mutated Gliomas Due to an Impairment in PARP1-Mediated DNA Repair
2-Hydroxyglutarate Produced by Neomorphic IDH Mutations Suppresses Homologous Recombination and Induces PARP Inhibitor Sensitivity
Prostate Cancer Researchers Find Genetic Fingerprint Identifying How, When Disease Spreads
Scientists Identify DNA Signature Linked to Prostate Cancer Severity
May 30, 2017 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Laboratory Testing
Few anatomical tools hold more potential to revolutionize the science of diagnostics than biomarkers, and pathologists and medical laboratories will be first in line to put these powerful tools to use helping patients with chronic diseases
There’s good news for both anatomic pathology laboratories and medical laboratories worldwide. Large numbers of clinically-useful new biomarkers continue to be validated and are in development for use in diagnostic tests and therapeutic drugs.
Clinical laboratories rely on biomarkers for pathology tests and procedures that track and identify infections and disease during the diagnostic process. Thus, trends that highlight the critical role biomarkers play in medical research are particularly relevant to pathology groups and medical laboratories.
Here’s an overview of critical trends in biomarker research and development that promise to improve diagnosis and treatment of chronic disease.
Emerging Use of Predictive Biomarkers in Precision Medicine
Recent advances in whole genome sequencing are aiding the development of highly accurate diagnostics and treatment plans that involve the development and use of Predictive Biomarkers that improve Precision Medicine (PM).
PM involves an approach to healthcare that is fine-tuned to each patient’s unique condition and physiology. As opposed to the conventional one-size-fits-all approach, which looks at the best options for the average person without examining variations in individual patients.
Predictive biomarkers identify individuals who will most likely respond either favorably or unfavorably to a drug or course of treatment. This improves a patient’s chance to receive benefit or avoid harm and goes to the root of Precision Medicine. (Image copyright: Pennside Partners.)
The National Institutes of Health (NIH) defines PM as “an emerging approach for disease treatment and prevention that considers individual variability in genes, environment, and lifestyle for each person.” It gives physicians and researchers the ability to more accurately forecast which prevention tactics and treatments will be optimal for certain patients.
Combining Drugs for Specific Outcomes
Cancer treatment will be complimented by the utilization of combination drugs that include two or more active pharmaceutical ingredients. Many drug trials are currently being performed to determine which combination of drugs will be the most favorable for specific cancers.
Combination drugs should become crucial in the treatment of different cancers treatments, such as immunotherapy, which involves treating disease by inducing, enhancing, or suppressing an immune response.
Biomarkers associated with certain cancers may enable physicians and researchers to determine which combination drugs will work best for each individual patient.
Developing More Effective Diagnostics
In Vitro diagnostics (IVDs) are poised for massive growth in market share. A report by Allied Market Research, states the worldwide IVD market will reach $81.3 billion by 2022. It noted that IVD techniques in which bodily fluids, such as blood, urine, stool, and sputum are tested to detect disease, conditions, and infections include important technologies such as:
Allied Market Research expects growth of the IVD market to result from these factors:
- Increases in chronic and infectious diseases;
- An aging population;
- Growing knowledge of rare diseases; and
- Increasing use of personalized medicines.
The capability to sequence the human genome is further adding to improvements in diagnostic development. Pharmaceutical companies can generate diagnostic counterparts alongside related drugs.
Biopsies from Fluid Sources
Millions of dollars have been spent on developing liquid biopsies that detect cancer from simple blood draws. The National Cancer Institute Dictionary of Cancer Terms defines a liquid biopsy as “a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood.”
At present, liquid biopsies are typically used only in the treatment and monitoring of cancers already diagnosed. Companies such as Grail, a spinoff of Illumina, and Guardant Health are striving to develop ways to make liquid biopsies a crucial part of cancer detection in the early stages, increasing long-term survival rates.
“The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage,” said Dr. Richard Klausner, Senior Vice President and Chief Medical Officer at Grail.
Grail hopes to market a pan-cancer screening test that will measure circulating nucleic acids in the blood to detect the presence of cancer in patients who are experiencing no symptoms of the disease.
Clinical Trials and Precision Medicine
The Precision Medicine Initiative (PMI), launched by the federal government in 2015, investigates ways to create tailor-made treatments and prevention strategies for patients based on their distinctive attributes.
Two ongoing studies involved in PMI research are MATCH and TAPUR:
- MATCH (Molecular Analysis for Therapy Choice) is a clinical trial run by The National Cancer Institute. The researchers are studying tumors to learn if they possess gene abnormalities that are treatable by known drugs.
- TAPUR (Targeted Agent and Profiling Utilization Registry), is a non-randomized clinical trial being conducted by the American Society of Clinical Oncology (ASCO). The researchers are chronicling the safety and efficacy of available cancer drugs currently on the market.
New Tools for Pathologists and Clinical Laboratories
The attention and funds given to these types of projects expand the possibilities of being able to develop targeted therapies and treatments for patients. Such technological advancements could someday enable physicians to view and treat cancer as a product of specific gene mutations and not just a disease.
These trends will be crucial and favorable for clinical laboratories in the future. As tests and treatments become unique to individual patients, pathologists and clinical laboratories will be on the frontlines of providing advanced services to healthcare professionals.
—JP Schlingman
Related Information:
5 Trends Being Impacted by Biomarkers
Immuno-Oncology Stories of 2016
Bristol-Myers Leads Immune-Oncology Race but Merck, Astrazeneca and Roche Still Have Contenders
Five Companies to Watch in the Liquid Biopsy Field
Illumina Spinoff GRAIL to Trial Liquid Biopsies for Early Detection of Cancer
Illumina Forms New Company to Enable Early Cancer Detection via Blood-Based Screening
A to Z List of Cancer Drugs
Personalized Medicine and the Role of Predictive vs. Prognostic Markers
Understanding Prognostic versus Predictive Biomarkers
NCI-MATCH Trial (Molecular Analysis for Therapy Choice)
Six Months of Progress on the Precision Medicine Initiative
Mar 8, 2017 | Compliance, Legal, and Malpractice, Digital Pathology, Laboratory Pathology, Laboratory Testing
Pathologists in medical laboratories creating laboratory-developed tests (LDTs) should be aware that some in the scientific community want more transparency about technology and methods
Developers of clinical laboratory tests and medical diagnostic technologies might soon be feeling the pressure to increase their push for transparency and standards that ultimately would make replication easier.
That’s thanks to a review project’s inability to reproduce results from three of five high-profile cancer studies.
The review project is called the Reproducibility Project: Cancer Biology and is a collaboration between network provider Science Exchange of Palo Alto, Calif., and the Center for Open Science in Charlottesville, Va. They attempted to independently replicate selected results from high-profile cancer biology papers in an open fashion. (more…)
Aug 31, 2016 | Laboratory Management and Operations, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Use of these new technologies creates opportunities for clinical laboratories and pathologists to add more value when collaborating with physicians to advance patient care
Ongoing improvements in point-of-care testing are encouraging one major academic medical center to apply this mode of testing to the diagnosis of hospital-acquired infections (HAIs). This development should be of interest to clinical laboratory professionals and pathologists, since it has the potential to create a different way to identify patients with HAIs than medical lab tests done in the central laboratory.
Massachusetts General Hospital (MGH), Harvard Medical School’s (HMS’) largest teaching hospital, has developed a prototype diagnostic system that works with doctors’ smartphones or mobile computers. The hand-held system can identify pathogens responsible for specific healthcare-acquired infections (HAIs) at the point of care within two hours, according to an MGH statement.
The researchers noted that 600,000 patients develop HAIs each year, 10% of which die, and that costs related to HAIs can reach $100 to $150 billion per year. However, as Dark Daily reported, the Centers for Medicare and Medicaid Services (CMS) does not reimburse hospitals for certain HAIs. (See Dark Daily, “Consumer Reports Ranks Smaller and Non-Teaching Hospitals Highest in Infection Prevention,” October, 30, 2015.) Thus, the critical need to identify from where the infection originated, which generates a significant proportion of samples tested at the clinical laboratories of the nation’s hospitals and health systems.
Therefore, pathologists and medical laboratory scientists will understand that shifting some of that specimen volume to point-of-care testing will change the overall economics of hospital laboratories.
Smartphone-based Genetic Test for HIAs
The MGH research team created a way to do accurate genetic testing in a simple device powered by a system they call Polarization Anisotropy Diagnostics (PAD). The system measures changes in fluorescence anisotropy through a detection probe’s recognition of bacterial nucleic acid, reported Medscape Medical News. More than 35 probes for detecting bacterial species and virulence factors are available.
Optical test cubes are placed on an electronic base station that transmits data to a smartphone or computer, where results are displayed. “In a pilot clinical test, PAD accuracy was comparable to that of bacterial culture. In contrast to the culture, the PAD assay was fast (under two hours), multiplexed, and cost effective (under $2 per assay), wrote the MGH researchers in the journal Science Advances. (more…)
Mar 28, 2016 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Federal agency hopes its open-source precisionFDA web portal will aid in development of laboratory-developed tests and inform regulatory decision-making
One recent initiative launched by the Food and Drug Administration (FDA) to foster the greater sharing of genetic information may be of some value to pathologists and clinical laboratory scientists who are developing laboratory-developed tests (LDTs) that incorporate molecular and genetic technologies.
The FDA unveiled an open-source platform for community sharing of genetic information. It is called precisionFDA, and the FDA describes its new web platform as an “online, cloud-based portal that will allow scientist from industry, academia, government, and other partners to come together to foster innovation and develop the science” of next-generation DNA sequencing processing. (more…)
