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|NEWS IN BRIEF
|Year : 2019 | Volume
| Issue : 2 | Page : 192-194
News in brief
|Date of Web Publication||2-May-2019|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. News in brief. Indian J Cancer 2019;56:192-4
| » Artificial Intelligence: the Next Big Strategy in Breast Cancer Screening|| |
The National Health Services (NHS), United Kingdom, has started looking at artificial intelligence (AI) solutions to tackle the critical and dangerous shortage of radiologists across the country.
With the advent of deep learning and its success in image classification tasks, there has been a tremendous interest in applying this technology in analysis of medical images, especially radiology scans. Many companies around the world claim to have developed deep learning–based AI algorithms that can detect early cancer on X-ray mammograms.
The UKs NHS Breast Screening Programme provides free breast cancer screening mammography every 3 years for all women in the United Kingdom from 50 and 71 years of age. All these mammograms are read by two radiologists. The shortage of radiologists is compromising the efficient delivery of this program. To address this, NHS is turning toward AI and conducting retrospective trials across the hospitals in its network.
Kheiron Medical, a London-based AI start-up, was the first UK company to receive the CE (Conformité Européene) mark for deep learning software in radiology. The company's algorithm will be retrospectively tested at NHS centers in Leeds and East Midlands. Dutch company ScreenPoint Medical and Google's DeepMind have also started similar trials with the NHS on mammography scans. These algorithms are developed by training convolutional neural networks (popularly referred to as CNN) on millions of mammograms along with their biopsy results. There have been accurate results on the limited validation studies done by these companies. Now, all these companies are testing their algorithms on tens of thousands of mammograms in NHS trust hospitals to determine whether they can be used to detect early signs of breast cancer with the same accuracy as a human radiologist.
The research team lead by Dr. Vasantha Kumar Venugopal [lead medical imaging researcher, Centre for Advanced Research in Imaging, Neuroscience and Genomics (CARING), the R&D division of Mahajan Imaging, a high-end diagnostic chain in New Delhi] is helping several groups in developing, validating, and even deploying AI algorithms. “Some of the AI solutions that we are validating both retrospectively and in controlled prospective conditions are showing immensely promising results. At our institute, we are convinced that in next couple of years, the way medical images are read will be radically transformed by AI. It is important that government agencies in our country take [the] cue from NHS and are proactive in bringing such solutions to improve healthcare services at our public hospitals.”
Mehvash Haider, New Delhi
| » FDA Approves first Immunotherapy Regimen for Breast Cancer|| |
Based on the IMpassion130 trial by Peter Schmid (Barts Cancer Institute, Queens Mary University of London) and colleagues which is published in the New England Journal of Medicine, the Food and Drug Administration (FDA) has granted accelerated approval to a combination of chemotherapy and antibody medications that train the patient's own immune system to attack cancer cells in PD-L1-positive, metastatic, triple-negative breast cancer (TNBC).
Breast cancer is a heterogeneous disease and has various subtypes. Clinically, these subtypes are characterized based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is an aggressive subtype which is defined by the lack of expression of ER, PR, and HER2. TNBC may account for up to 20% of all invasive breast cancer types. TNBC is encountered frequently in younger women of Hispanic and African-American descent and those with a BRCA1 gene mutation and is often associated with advanced disease.
Normally, the immune system does not attack cancer cells because they are viewed as a part of the body. Atezolizumab is a monoclonal antibody that attaches to the cancer cell and inactivates a protein called Programmed Death Ligand 1 (PD-L1) which is responsible for making the immune system identify the cancer cells as “self.” In this phase III trial sponsored by Roche, 902 patients with untreated TNBC received nab-paclitaxel with or without atezolizumab, a monoclonal antibody that targets PD-L1 and prevents interaction with Programmed Death 1 (PD-1) and B7-1 (also known as CD80), a costimulatory cell surface protein. Through this mechanism, T-cell suppression is reversed, leading to an antitumor effect [Figure 1].
|Figure 1: Blocking the PD1/PDL1 interaction allows the T cell to destroy cancer cell|
Click here to view
FDA's decision to grant the treatment accelerated approval was based on extended progression-free survival which is the time interval in which a patient's cancer does not worsen.
In the opinion of Dr. Jamal A. Khan (Director, Denvax Clinic and Lab), who is a pioneer in dendritic cell immunotherapy in India, “PD-L1 receptor blockers are thriving [in] the market and they show marginal improvement as compared to standard line of care in triple negative breast cancer patients with M1 pathological status.”
Commenting on the challenges, he said “I have yet to see patients who are on this drug and responding to it according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. The cost of this therapy is again a big challenge in Indian context.”
Drug companies are under the stipulation to undertake phase 4 confirmatory trials to confirm the anticipated clinical benefits. Thus far, FDA has only granted approval for a drug only when the confirmatory trial shows that the drug actually provides a clinical benefit.
| » Circadian Rhythm Disruption: a New Risk Factor for Cancer|| |
The age-old advice of “early to bed, early to rise” may just have been proven to be correct. In an article published in Cancer Medicine in January 2019, by Zekun Liu and colleagues titled “Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers,” the researchers attempted to decipher the “circadian-cancer interplay” on a large number of human cancer samples.
“Circa diem” in Latin means “about a day.” A master time keeper in the hypothalamus controls rhythmicity of mammalian body at organ, cellular, and genetic level. The periodicity of menstrual cycles, dusk–dawn phenomenon, and sleep–wake cycles are indubitable instances of the biological clock. With the advent of electricity, the escape from sunlight dependency has altered human behavior, predominantly by increasing the duration of exposure to light. In fact, the discovery of the molecular mechanisms controlling circadian rhythm had resulted in researchers Jeffrey C. Hall, Michael Rosbash, and Michael W. Young receiving the Nobel Prize in Physiology or Medicine in 2017.
For decades, the relationship between biological clock disruption (e.g., night shift, jet lag) and carcinogenesis had been postulated. Many genes (e.g., PER1/2/3, CLOCK, CRY1/2, and ARNTL) are found to be linked with circadian rhythm. Liu et al. analyzed 1350 circadian genes for 20 different cancers, for genetic aberrations and expression profiles. They found that circadian genes have important roles in not only tumor suppression but also alterations in these genes and their expression may alter the cancer behavior. The core clock genetic expression was measured by “circadian clock index (CCI).” This study revealed that the number of alterations in clock genes was low, but that the expression levels, measured as CCI, were downregulated by the higher levels of DNA methylation in most tumors.
The circadian rhythm has been proposed to have tumor-suppressive action that is disrupted in cancers. Circadian rhythm disruption has been implicated in cancers of prostate, breast, endometrium, liver, lung, colon, rectum, and in leukemias. This study also showed it as an important immune regulator. For example, transendothelial leucocyte migration, cytokine receptor interaction, and chemokine signaling cascades were more upregulated in high CCI samples than lower ones. CCIs of the core clock genes were corroborative to the immune phenotypes and survival, although the correlation was not consistently positive or negative among cancer types. The authors concluded that further investigations are needed to elucidate the mechanisms and functions of the circadian disruption in various cancer types.
International Agency for Research on Cancer (Lyon, France) has listed “shift work involving circadian disruption” as probably (category 2A) carcinogenic. Circadian clock genetics may play a crucial role in advancing the development of potential preventive and therapeutic oncological strategies. The results of a multitude of studies in this exciting and potential field will shed more light on this “light-circadian-cancer” story.
HS Darling, New Delhi
| » Oversupply of Energy Proven to Be the Unifying Mechanism of Many Cancer Risk Factors|| |
A study published by Daniel Wu [Figure 2], Athena Atipis, and John Pepper in Evolution, Medicine, and Public Health in January 2019 suggests that the single unifying mechanism behind many cancer risk factors is “oversupply of energy.” A computer-based simulation model to track every single cell and their properties was designed for this study. The hypothesis behind the study, called as the “metabolic cancer suppression hypothesis” states that normally organisms suppress oncogenesis by strict regulation of energy supply to the somatic cells. Senior researcher and a coauthor of the study, John W Pepper from the National Cancer Institute, Bethesda, USA, explained the hypothesis in a mail to this correspondent, as follows: “Somatic (body) cells can't proliferate abnormally, and so can't evolve into cancer, unless they have access to abnormally high levels of energy resources to support abnormally rapid proliferation. The human body is 'designed' to deny somatic cells access to abnormally high levels of energetic resources, which helps to suppress cancer. When any pathological condition provides cells with access to abnormally high levels of energetic resources, cancer risk is greatly increased in the affected tissues.”
|Figure 2: Daniel Wu, the chief investigator of the article.|
Credit: John W Pepper, PhD, NCI
Click here to view
Besides somatic mutations and clonal selection, another important factor that plays in oncogenesis is selective micro-environment. It must be noted that the difference in normal and cancer cells lies in what mutations are selected after they occur. Since selection of micro-environment is difficult to quantify, its evolution with regard to role in oncogenesis has been slower than other factors. Both hyperglycemia and vasodilation lead to energy oversupply and trigger oncogenesis by inhibiting the cancer suppression mechanisms [Figure 3].
|Figure 3: The mechanism of action of multiple risk factors of cancer.|
Credit: John W Pepper, PhD, NCI
Click here to view
Dr. Pepper also mentioned that the study unifies the mechanisms underlying many cancer risk factors. He added, “Many superficially different cancer risk factors may converge on this causal mechanism, so understanding it may unify our approach to cancer prevention.” For example, alcohol, one of the important risk factors for cancers, causes vasodilation, thereby causing energy oversupply. Similarly, increased calorie intake, hyperglycemia, obesity, and chronic inflammation which are the risk factors for many cancers act by the common mechanism of “energy oversupply” encouraging oncogenesis [Figure 4]. Like this, many other risk factors could in future be brought down to the unifying mechanism of “energy oversupply.”
He summarized the significance of the study as follows: “The most important implications are probably of cancer prevention, rather than cancer therapy. That's good, because cancer prevention is much to be preferred over cancer therapy. If this 'metabolic cancer suppression hypothesis' hypothesis is supported by empirical testing, it can serve as a guide the design and evaluation of interventions to reduce the risk of many different cancers.”
The study concluded that dietary restriction could be a powerful tool in cancer prevention as it causes the cells to preserve energy by halting cell proliferation which is an energy expending activity and using the available energy for maintenance only thereby decreasing the incidence of oncogenesis.
Neha Chauhan, Bangalore
[Figure 1], [Figure 2], [Figure 3], [Figure 4]