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Manisit Das
Pancreatic Cancer remains one of the few cancers against which we haven’t found a treatment that offers long-term benefit. Currently, less than one in ten patients will survive five years past the point of diagnosis. Like any other cancer, early diagnosis can improve treatment options and patient survivability. However, due to the lack of techniques to detect pancreatic tumors at their earliest stages, the cancer will not be diagnosed until the tumor reaches an advanced stage.
A recent study noted distinct changes in factors related to patient’s health, like blood sugar and body temperature, as early as thirty months before cancer diagnosis. These results can be useful in improving the screening strategy for patients with high-risk of pancreatic cancer, while early diagnosis can go a long way in extending the lifetime of an individual.
Sah et al. at Mayo Clinic investigated the clinical data of pancreatic cancer patients from Olmsted County, Minnesota, in the five years before pancreatic cancer diagnosis. They used noncancer patients, adjusted for age and sex, as controls for their analyses. They found that blood sugar increases between 30-18 months before the cancer diagnosis, which further becomes a stronger pattern along with the reduction of body weight and lipid in blood serum in the 18-6 months span. In the 6 months leading to diagnosis, patients develop symptoms of the disease, while the patterns seen in the earlier months become even more prominent.
Seeing the trends of weight loss before diagnosis, the researchers wanted to more deeply investigate the changes in the muscle and tissue composition of the patients. They found a reduction in fat, followed by a decrease in skeletal muscles in the months leading to cancer diagnosis. They suspected that signaling from the cancer cells is behind the alterations in fat tissues and cells.
To gather experimental evidence supporting their idea, they conducted mouse studies where they isolated ‘exosomes’ from pancreatic cancer cells. Exosomes are tiny sacs containing protein and nucleic acids, which are secreted by cells, and used for communicating with other cells and influencing their behavior. The exosomes originating from the pancreatic cancer cells in mice influenced the behavior of the fat cells, changing them to a brown subtype associated with higher energy production, and potentially aiding in wasting. Hence, it is possible that a similar signaling from the exosomes in the human pancreatic cancer patients caused the decrease in weight.
These warning signs, uncovered by Sah and colleagues, are valuable insights. However, there are some limitations of the inferences, hindering incorporation of these strategies into clinical practice. Firstly, the study was conducted retrospectively, where the outcome of the patients was already known, and the analyses looked backward and explored potential risk factors. These kinds of studies often introduce errors in results, due to biases and influences by other variables. The differences in the factors measured in cancer vs non-cancer patients were not starkly different. This will make it difficult to pick up these signals from a general population and pinpoint patients at risk. Further, as the authors themselves pointed out, Olmsted County, from where the data is obtained is predominantly White, and the signatures of metabolism, the life-sustaining processes, which were identified as changing factors, can have racial differences. Therefore, the study needs to be repeated from data obtained in patients from a community which is more diverse to ensure that the warning signs hold true across the general patient population.
The work of Sah and colleagues presents additional factors that can be incorporated while performing a targeted screening of patient cohorts known to carry a high risk for pancreatic cancer. For a disease where we still lack accurate and sensitive early detection tests, this is definitely a impactful study and we hope that these metabolic changes observed in individuals prior to pancreatic cancer onset can be used to intercept the disease early and improve the survival of patients.
Works Discussed:
1. Sah, R. P., Sharma, A., Nagpal, S., Patlolla, S. H., Sharma, A., Kandlakunta, H., . . . Chari, S. T. (2019). Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma. Gastroenterology. doi: 10.1053/j.gastro.2019.01.039
2. Khalaf, N., & Wolpin, B. M. Metabolic Alterations as a Signpost to Early Pancreatic Cancer. Gastroenterology. doi: 10.1053/j.gastro.2019.03.028
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