All these technologies show amazing promise and some of them are already in use. The scientific community in India is constantly pushing their limits to get to a stage where the diagnosis of cancer will not be a life-altering event for patients
In the last few decades, cancer has become a leading cause of mortality worldwide. According to the WHO, currently, around 10 million new cancers are diagnosed each year worldwide, but unless there is an effective prevention campaign, the number will rise to 20 million in the next 17 years’ time. Therefore, the global scientific and healthcare community are turning to novel approaches in an attempt to make sure those grim projections don’t continue to haunt us. Stronger and effective cancer treatments are certainly part of the development goals, but a premium is also being put on early diagnosis to ensure better medical outcomes and assured prevention.
Today, more focus is given to precision medicine-quantitation, multiplexing and highly precise identification of markers. Precise tools which were once utilised in research settings are now applied in clinical practice with just one goal in mind- faster and more efficient cancer testing.
In this article, we examine top technologies that will improve efficiencies and precision in cancer diagnostics and prevention in India.
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Fluid biopsies: Many scientific publications have documented that liquid or fluid biopsies are informative regarding response to a given therapy, are capable of detecting relapse with lead time compared to standard measures, and reveal mechanisms of resistance. According to Dr BS Ajaikumar, Chairman and CEO, HCG Global, liquid biopsy plays a significant role in those cases where it is difficult to establish a tissue diagnosis in a recurrent or metastatic setting. It is a simple minimally invasive procedure done on blood, plasma or urine sample to identify the genetic material of tumour cells either as ctDNA (Circulating tumour DNA) or CTC (Circulating Tumour cells) or cfDNA (Cell-free DNA) by identification of cancer-associated DNA / RNA / exosomes.
He further lists down some benefits of the same:
- It predicts response to targeted therapy with mutational load and by identifying specific, existing as well as new mutations. It is already in use for choosing targeted drug therapies in advanced stages of malignancies as in non-small-cell lung carcinoma (NSCLC). The US FDA approved the first liquid biopsy test in 2016 in NSCLC as a companion diagnostics test for exon 19 and exon 21 in EGFR, which is seen in 10-20 per cent of patients. About 60 per cent of these patients with known mutations (deletions), when followed up, are likely to develop additional mutations such as EGFR T790M indicative of resistance to the targeted drug therapy. So, the treatment can be modified accordingly with Osimertinib, even before the clinical evidence of failure to respond is evidence. Such detection is possible by liquid biopsy.
- It indicates prognosis through quantification of the ctDNA and residual mutational load as well as the type of mutation. It helps in detecting residual or recurrence or relapse of disease even in radiologically negative cases.
- Trials are underway to apply this technology for identification of mutations and targeted drug therapies in KRAS/NRAS in colon cancer, PIK3CA and resistant ALK in NSCLC. It has a role in the detection of clonal evolution and drug responses to targeted agents, especially by following mutations such as KRAS, NRAS, BRAF, TP53 and PIK3CA.
- Liquid biopsy using ctDNA is very useful for targeted therapy, follow up of these patients while on treatment and for early detection of recurrence/metastasis.
- Some trials have also confirmed the prognostic significance of CTCs in metastatic breast cancer. Studies are underway to evaluate the role of CTCs in identifying hormone-positive metastatic breast cancer patients who would benefit from early chemotherapy in comparison to hormonal therapy.
Real-time cancer diagnostics: With the need to need to translate recent discoveries in oncology research into clinical practice, cancer experts believe that objective, robust and cost-effective molecular techniques for clinical trials and, eventually, routine use is a must. Real-time PCR has become a useful and cost-effective technique for tumour profiling among clinical laboratories.
Dr Kirti Chadha, Head of Laboratory at Metropolis Healthcare expounds, “The pathogenesis of tumours is complex making the surgical management more difficult. Here comes the role of real-time diagnostics which will give an on-table diagnosis to make the treatment successful. A lot of research is going on it like an intelligent surgical knife has been developed by using an old technology where an electrical current heats tissue to make incisions with minimal blood loss, but with this technology, the vapourised smoke is analysed by a mass spectrometer to detect the chemicals in the biological sample allowing identification of malignant tissue. Also, a robotic platform has been developed in treating lung cancer. It combines robotics, software, data science and endoscope innovation to help diagnose lung cancer at an early stage with more accuracy and a lower risk of complications. Similarly, real‐time detection of breast cancer at the cellular level by a multispectral confocal scanning system has been developed. These are at research levels or some of them are being approved for use. Introducing advanced technology to traditional methods can also give us better real-time solutions like using digital pathology.”
Digital PCR: Digital PCR is the latest and advanced iteration of a conventional quantitative RT-PCR for sensitive and accurate measurement of DNA/RNA from samples. The primary principle behind the technique is similar to q-PCR but differs in the way the sample target is analysed.
Dr Dheeraj Gautam, Head of Department – Department of Histopathology, Associate Director- Department of Pathology and Lab Medicine, Medanta- The Medicity says, “PCR is a common test used to make many copies (millions or billions) of a particular region of DNA. With best systems, we have the capability to detect as few as ~10 copies of DNA templates. It is routinely used in DNA cloning, cancer diagnostics, and forensic analysis of DNA. For example, it might be a DNA sequence (gene) from a crime scene to match crime suspect, by forensic scientists. Typically, the goal of PCR is to amplify enough of the target DNA region, so that it can be analysed to deliver useful scientific information. Presently, Coronavirus is being tested by this method.”
Adding to this, Dr Ajaikumar informs, “Digital PCR is a simple and reproducible technique that does not rely on a calibration curve for sample target quantification. Digital PCR works by partitioning a sample of DNA into many individual, parallel PCR reactions. Following PCR amplification, the number of positive vs negative reactions is determined and the absolute quantification of target calculated using Poisson statistics. The benefits are, high precision, better signal to noise ratio, removal of PCR efficiency bias and simplified quantification.”
Speaking about the areas in which Digital PCR is currently applied, Dr Chadha reveals, “dPCR is currently being applied for absolute allele quantification, rare mutation detection, analysis of copy number variations, DNA methylation, and gene rearrangements in different kinds of clinical samples. The form of digital PCR ie. Digital droplet PCR(ddPCR) is performed in Metropolis for circulating tumour DNA(ctDNA), EGFR/KRAS/NRAS/BRAF mutations in lung and colorectal cancer.”
Source: Express Healthcare