New Study may Improve Treatment of Intestinal Tumours

Patients with neuroendocrine tumours that have spread beyond the intestines should not have surgery before they present with abdominal-related symptoms. This is shown in a new study by researchers at Uppsala University, who hope the results will have major significance, especially for the many patients who may run a reduced risk of unnecessary surgeries and complications in the future.

intestinal tumours, molecular scissors, disease, genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

Cancer care guidelines have long stipulated that patients with smaller neuroendocrine intestinal tumours should have surgery as soon as a tumour is detected. Now a new study from researchers at Uppsala University shows that surgical procedures carried out before the patient presents with abdominal-related symptoms have no impact on survival length. However, they do entail increased risk of complications, including in the form of intestinal obstruction, which may result in the need for additional surgery.

“The course of events is relatively common, because small neuroendocrine tumours are often first detected when they have spread beyond the intestine, usually to the liver, and surgery is then recommended promptly. But in our study, we followed up 363 patients who have been treated since 1985, and we found nothing to indicate that surgery carried out within six months after receiving a diagnosis produces better results than nonsurgical treatment until the patient presents with abdominal-related symptoms, such as pain or signs of intestinal obstruction,” says Peter Stålberg, Adjunct Professor and one of the authors of the new article.

The findings may soon have an impact on cancer care practice, as the Swedish guidelines for treatment will be reviewed in autumn 2017 and the European guidelines will be reviewed in 2018.

“We hope our findings have major significance, partly through more effective use of care resources, but above all, for the many patients who will run a reduced risk of unnecessary surgeries and complications in the future,” says Olov Norlén, another author of the study.

The researchers behind the findings are now preparing a new study in which they will carry out further comparisons of effects between early surgical measures and waiting on surgery until the patient presents with abdominal-related symptoms.

Full article: Kosmas Daskalakis, Andreas Karakatsanis, Ola Hessman, Heather C. Stuart, Staffan Welin, Eva Tiensuu Janson, Kjell Öberg, Per Hellman, Olov Norlén, Peter Stålberg (2017). Association of a Prophylactic Surgical Approach to Stage IV Small Intestinal Neuroendocrine Tumors With Survival, JAMA Oncol. doi:10.1001/jamaoncol.2017.3326

Source : Uppsala University