Innovative technologies for new methods of cancer detection
Anywhere, from 15% to 28% of cancer diagnoses are misleading. This was the alarming conclusion of an Exploring Diagnostic Accuracy in Cancer survey conducted at late 2012 by the US National Coalition of Health Care and Best Doctors .
The traditional methods of cancer diagnostics such as, e.g., mammography (for breast cancer), CT scans, X-ray, ultrasound imaging, MRI and PET (for various other types of cancer) or endoscopy, followed by biopsy of suspicious tissue (in case of gastrological cancer) could be traumatic and still are not 100% reliable. The US National Cancer Institute study revealed that of all breast cancer cases detected by screening the mammograms, up to 54% are estimated to be the result of overdiagnostics. Overdiagnosis can expose a woman to such risks as surgical deformity or toxicities from radiation therapy, hormone therapy or chemotherapy and late effects of therapeutic radiation (new cancers, scarring, or cardiac toxicity).
Obviously, new methods of precise and early cancer diagnostics and treatment without exposing patients to the danger of radiation, chemotherapy or surgical interventions are badly required. The evolution of nanotechnologies is promising to generate ones.
Nanoparticles, those tiny functional systems less than 100 nanometers, were first envisioned as early as in 1959 by the famous US physicist Richard Feynman. Encapsulated into biosensors (nanotubes, smart pills or patches) implanted into the human body, nanoparticles are able to “recognize” the so called “biomarkers”, those early indicators of the diseased cells, such as fragments of a protein, DNA or RNA-based. Upon receiving biological signals produced by damaged cells (e.g. fluorescent, heat, oxygen or other manifestations of metabolic changes associated with a disease) these sensors can transmit information wirelessly to respective physicians.
Thus, the researchers from the Massachusetts Institute of Technology (MIT) have designed a carbon nanotube sensor that can be implanted under the skin for over 1 year to detect a molecule of nitric oxide (NO), a signaling molecule within living cells that carries messages between the brain and immune system functions. In case of cancerous cells, the ordinary levels of NO are disturbed.
Carbon nanotubes can have a natural fluorescence, and when they attach themselves to a certain target, brighten or dim. Short term nanosensors are injected into the blood stream and when injectable on mice are passing through the lungs and heart or gather in the liver, without causing damage on the way. Once in the liver, the sensors are able to monitor NO. The other sensor is covered by alginate gel and implanted under the skin for a period of 400 days or potentially even longer. When both sensors are in the body, they produce a near-infrared fluorescent signal by shining a tiny laser on them. This information is then passed to an instrument that detects the difference between the nanotubes and other areas that may give off fluorescence.
Millions of women are taking annual mammogram screening for a fear of breast cancer. During the procedure the breast tissue is squeezed firmly between two plates. This is not only painful, but can damage small blood vessels resulting in existing cancerous cells spreading to other areas of the body.
To make breast cancer test easier Reno, a Nevada-based company, has designed a wearable sensor that could be inserted into the women’s bra. The sensor detects tiny metabolic temperature changes caused by cancerous cells in a tumor. The temperature readings are sent back to a global library where they’re run through a proprietary algorithm. A woman can wear the garment for a few hours, and the information will be automatically communicated to her physician. Researchers claim that the breast sensor bra may work even better than a mammogram for patients in the early stages of cancer or with dense breast tissue, a condition affecting over half of all women.
El Camino Hospital in Bay Area is currently running clinical trials with Cyrcadia Health iTBra. A tiny patch inserted in the bra tracks temperature changes within two hours sending information to a physician via a smart phone. Women can perform breast cancer diagnostics in their home not being subjected to an unpleasant mammogram test. If trials proved to be successful the Cyrcadia Health hopes to have the iTBra on the market later this year.
Blood test can already alert us on many potential disorder such as liver damages with Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) enzyme concentration analysis or creatinine level to spot kidney disorders. Why not cancer? Unfortunately due to the impact of multiple ingredients contained in the blood such as proteins and ions, the detection of a specific cancer biomarkers is not easy. Usually such analysis are carried in the controlled laboratory environments.
The first attempt to detect cancer biomarkers in the whole blood was done by the team led by Mark Reed, Yale’s Harold Hodgkinson Professor of Engineering & Applied Science, and Tarek Fahmy, an associate professor of biomedical and chemical engineering. The researchers used nanowire sensors to measure concentrations of two specific biomarkers: antigens specific to prostate and breast cancer. The sensor works as a filter: catching the biomarkers on a chip while washing away the rest of the blood.
With this method researchers are able to detect extremely small concentration of antigens at the range of picograms per milliliter, equivalent to something like a single grain of salt dissolved in a large swimming pool. Should such methods be successful, we would be able in the near future to receive a preliminary alert of oncological disorders by a familiar blood test.
Nanosensors may allow not only to detect, but to treat the disease. Researchers from the Tel Aviv University under supervision of Prof. Dan Peer invented a novel method of treating aggressive forms of blood cancer such as Mantle Cell Lymphoma (MCL). The researchers noticed that MCL is associated with the intensified activity of a certain gene, namely the gene CCND1. When over-expressed, the CCND1 gene produces too much of a Cyclin D1 protein, sometimes 3,000 – 15,000 times too many. To reduce and regulate protein production the scientists have invented the CCND1 blocker: the synthetic strand of RNA molecules (siRNA). By targeting RNA molecules that convey genetic information from the DNA to the ribosomes, the inner-cell structures where new protein chain are assembled (translated) from amino acids, siRNA disables its ability to express a specific gene. To deliver siRNA precisely to CCMD1 gene, it is loaded into the lipid-based nanoparticles (LNPs) coated with antibodies. Scientists believe that such method could be applied not only for MCL but also for other malicious forms of cancer. The results of the study were published in the journal Proceedings of the National Academy of Sciences of the USA.
Another form of cancer that is developing almost unnoticeably is a lung cancer. Traditional methods to diagnose lung cancer such as bronchoscopies, computer-guided biopsies or surgery are invasive and may cause additional harm to patients. Breath analyzers provide a method of detecting lung and other form of cancer (e.g., gastroenterological types of cancer) by simply “sniffing” cancer in the breath. Coated with tiny nanowires, these sensors can identify miniscule amounts of chemical compounds exhaled with the breath thus measuring the concentration of cancer biomarkers contained in those components.
The Israel Institute of Technology of researchers under Prof. Hossam Haick can analyze more than 1,000 different gases contained in the breath that may indicate various illnesses. For example, by analyzing the concentrations of eight specific substances (out of 130) in the oral cavity, the technology allowed the researchers to distinguish between the patients suffering from gastric cancer and the healthy individuals with 92% accuracy.
Will such technologies finally reach people who are anxiously waiting for more reliable and accessible methods of cancer diagnostics and treatment? The success and acceptance of such methods depend on manifold skills of computer scientists, biochemical engineers, physicist, biologists and physicians thus requiring tight cooperation across multiple professional organizations. When such cooperation has been achieved, it can lead to stunning discoveries that potentially will save millions of lives.