List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
Scientists reported positive Phase 1 trial results of their “intratumoral microdevice” in patients with glioma tumors
Here is an example of new microtechnology which has the potential to greatly shorten the time and improve the ability of physicians to determine which anti-cancer drug is most effective for an individual patient’s glioblastoma. As it is further developed, this technology could give anatomic pathologists and clinical laboratories an increased role in assessing the data produced by microdevices and helping physicians determine the most appropriate anti-cancer drug for specific patients.
In a news release, researchers at Brigham and Women’s Hospital (BWH) in Boston said they have developed an implantable “intratumoral microdevice” (IMD) that functions as a “lab in a patient,” capable of gauging the effectiveness of multiple drugs that target brain tumors. In a Phase 1 clinical trial, they tested the IMD on six patients with glioma tumors.
“In order to make the greatest impact on how we treat these tumors, we need to be able to understand, early on, which drug works best for any given patient,” study co-author Pier Paolo Peruzzi, MD, PhD, told the Harvard Gazette. “The problem is that the tools that are currently available to answer this question are just not good enough. So, we came up with the idea of making each patient their own lab, by using a device which can directly interrogate the living tumor and give us the information that we need.”
Peruzzi is Principal Investigator at the Harvey Cushing Neuro-Oncology Laboratories and Assistant Professor of Neurosurgery at Harvard Medical School.
“Our goal is for the placement of these devices to become an integral part of tumor surgery,” said Pier Paolo Peruzzi, MD PhD (above) of Brigham and Women’s Hospital and Harvard Medical School in an article he co-wrote for Healio. “Then, with the data that we have from these microdevices, we can choose the best systemic chemotherapy to give to that patient.” Pathologists and clinical laboratories may soon play a role in helping doctors interpret data gathered by implantable microdevices and choose the best therapies for their patients. (Photo copyright: Dana-Farber Cancer Institute.)
New Perspective on Tumor Treatments
In a news story he co-wrote for Healio, Peruzzi explained that the microdevice—about the size and shape of a grain of rice—contains up to 30 tiny reservoirs that the researchers fill with the drugs they want to test. Surgeons implant the device during a procedure to remove the tumors.
The surgery takes two to three hours to perform, and during that time, the device releases “nanodoses” of the drugs into confined areas of the tumor. Near the end of the procedure, the device is removed along with tissue specimens. The researchers can then analyze the tissue to determine the effectiveness of each drug.
“This is not in the lab, and not in a petri dish,” Peruzzi told Harvard Gazette. “It’s actually in real patients in real time, which gives us a whole new perspective on how these tumors respond to treatment.”
The Healio story notes that gliomas are “among the deadliest brain cancers and are notoriously difficult to treat.” With current approaches, testing different therapies has posed a challenge, Peruzzi wrote.
“Right now, the only way these drugs are tested in patients is through what are called window-of-opportunity studies, where we give one drug to the patient before we resect the tumor and analyze the effect of the drug,” he said. “We can only do this with one drug at a time.”
Determining Safety of Procedure
The primary goal of the Phase 1 trial was to determine the safety of the procedure, Peruzzi noted. “To be in compliance with standard clinical practice and minimize risks to the patients, we needed to integrate the placement and retrieval of the device during an otherwise standard operation.”
The trial consisted of three men and three women ranging from 27 to 86 years old, with a median age of 76. Five were diagnosed with glioblastoma and one with grade 4 astrocytoma.
“None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens,” the researchers wrote in Science Translational Medicine. They noted that application of the IMD added about 32 minutes to the time required for the surgery, equating to a cost increase of $7,800.
One drug they tested was temozolomide (TMZ), “the most widely used agent in this patient population,” they wrote. “Several patients in our trial received it systemically, either before or after IMD insertion, as part of the standard of care. Thus, although our trial was not designed to choose chemotherapy agents based on IMD data, we still could compare the observed clinical-radiological response to systemic TMZ with the patient-specific response to TMZ in the IMD-exposed tissue.”
One patient, the researchers noted, had not benefited from the drug “in concordance with the poor tissue response observed in the IMD analysis.” But in another patient, a 72-year-old woman, “IMD analysis showed a marked response to TMZ,” and she survived for 20 months after receiving the treatment “with radiological evidence of tumor response. This was despite having a subtotal tumor resection, in itself an unfavorable prognostic factor. The patient expired because of an unrelated cardiovascular event, although she had remained neurologically stable.”
Drug Duration Limitation
One limitation of the study was that testing the device during the tumor removal procedure limited the duration of the drug treatments, Peruzzi said. The Harvard Gazette noted that following their initial study, the researchers were testing a variation of the procedure in which the device is implanted three days before the main surgery in a minimally invasive technique. This gives the drugs more time to work.
Cancer researchers have theorized that common treatments for tumors can impair the immune system, Peruzzi wrote in Healio. “One thing we want to look at is which drugs can kill the tumor without killing the immune system as well,” he noted.
Future studies will determine the effectiveness of implanting microdevices into tumors to test therapies in vivo. Should they become viable, clinical laboratories and anatomic pathologists will likely be involved in receiving, interpreting, storing, and transmitting the data gathered by these devices to the patient’s doctors.
MicroRNAs in urine could prove to be promising biomarkers in clinical laboratory tests designed to diagnose brain tumors regardless of the tumor’s size or malignancy, paving the way for early detection and treatment
Researchers at Nagoya University in Japan have developed a liquid biopsy test for brain cancer screening that, they claim, can identify brain tumors in patients with 100% sensitivity and 97% specificity, regardless of the tumor’s size or malignancy. Pathologists will be interested to learn that the research team developing this technology says it is simple and inexpensive enough to make it feasible for use in mass screening for brain tumors.
Neurologists, anatomic pathologists, and histopathologists know that brain tumors are one of the most challenging cancers to diagnose. This is partly due to the invasive nature of biopsying tissue in the brain. It’s also because—until recently—clinical laboratory tests based on liquid blood or urine biopsies were in the earliest stages of study and research and are still in development.
Thus, a non-invasive urine test with this level of accuracy that achieves clinical status would be a boon for the diagnosis of brain cancer.
Researchers at Japan’s Nagoya University believe they have developed just such a liquid biopsy test. In a recent study, they showed that microRNAs (tiny molecules of nucleic acid) in urine could be a promising biomarker for diagnosing brain tumors. Their novel microRNA-based liquid biopsy correctly identified 100% of patients with brain tumors.
Atsushi Natsume, MD, PhD (above), Associate Professor at Nagoya University, led the research team that created the simple, liquid biomarker urine test for central nervous system tumors that achieved 100% sensitivity and 97% specificity, regardless of the tumor’s size or malignancy. Such a non-invasive clinical laboratory test used clinically would be a boon to brain cancer diagnosis worldwide. (Photo copyright: Nagoya University.)
Well-fitted for Mass Screenings of Brain Cancer Patients
According to the National Cancer Institute (NCI), brain and other central nervous system (CNS) cancers represent 1.3% of all new cancer cases and have a five-year survival rate of only 32.6%.
In their published study, the Nagoya University scientists wrote, “There are no accurate mass screening methods for early detection of central nervous system (CNS) tumors. Recently, liquid biopsy has received a lot of attention for less-invasive cancer screening. Unlike other cancers, CNS tumors require efforts to find biomarkers due to the blood–brain barrier, which restricts molecular exchange between the parenchyma and blood.
“Additionally, because a satisfactory way to collect urinary biomarkers is lacking, urine-based liquid biopsy has not been fully investigated despite the fact that it has some advantages compared to blood or cerebrospinal fluid-based biopsy.
“Here, we have developed a mass-producible and sterilizable nanowire-based device that can extract urinary microRNAs efficiently. … Our findings demonstrate that urinary microRNAs extracted with the nanowire device offer a well-fitted strategy for mass screening of CNS tumors.”
The Nagoya University researchers focused on microRNA in urine as a biomarker for brain tumors because “urine can be collected easily without putting a burden on the human body,” said Atsushi Natsume, MD, PhD, Associate Professor in the Department of Neurosurgery at Nagoya University and a corresponding author of the study, in a news release.
A total of 119 urine and tumor samples were collected from patients admitted to 14 hospitals in Japan with CNS cancers between March 2017 and July 2020. The researchers used 100 urine samples from people without cancer to serve as a control for their test.
To extract the microRNA from the urine and acquire gene expression profiles, the research team designed an assembly-type microfluidic nanowire device using nanowire scaffolds containing 100 million zinc oxide nanowires. According to the scientists, the device can be sterilized and mass-produced, making it suitable for medical use. The instrument can extract a significantly greater variety and quantity of microRNAs from only a milliliter of urine compared to traditional methods, such as ultracentrifugation, the news release explained.
Simple Liquid-biopsy Test Could Save Thousands of Lives Each Year
While further studies and clinical trials will be necessary to affirm the noninvasive test’s accuracy, the Nagoya University researchers believe that, with the inclusion of additional technologies, a urine-based microRNA test could become a reliable biomarker for detecting brain tumors.
“In the future, by a combination of artificial intelligence and telemedicine, people will be able to know the presence of cancer, whereas doctors will be able to know the status of cancer patients just with a small amount of their daily urine,” Natsume said in the news release.
Biomarkers found in urine or blood samples that provide clinical laboratories with a simple, non-invasive procedure for early diagnosis of brain tumors could greatly increase the five-year survival rate for thousands of patients diagnosed with brain cancer each year. Such diagnostic technologies are also appropriate for hospitals and physicians interested in advancing patient-centered care.
