Scientists have identified a “molecular signature” (IFNAP) that predicts the sensitivity of liver cancer to immunotherapy drugs, a possible new pre-operative strategy that is very important for patients
There are two studies that identify for the first time which patients with liver tumors can undergo neo-adjuvant (ie preoperative) immunotherapy with a high probability of success. Both represent a real turning point that can change the fate of those affected by this type of tumor, a significant paradigm shift, which opens up the possibility of liver transplantation even to those cases that until now could not have benefited from it due to of the severity of the disease.
The two studies
«The scientific works we have carried out are two, synergistic with each other – explains Vincenzo Mazzaferro, director of the Complex Structure of Hepato-Gastro-Pancreatic Surgery of the National Cancer Institute of Milan (INT) and professor of surgery at the University of Milan (UniMi) –. The study published in Gastroenterology identified a predictive molecular signature called IFNAP, which is made up of the combination of eleven genes. This ‘signature’, identified on the tumor biopsy, predicts the sensitivity of liver cancer tumor cells to the anti-PD1 class of immunotherapy drugs, regardless of the origin of the tumor itself. A prognostic biopsy was therefore used, ie capable of predicting the effectiveness of the drugs that could be administered. «However, we also wanted to investigate the possibility of using the liquid biopsy, that is, extracting the fragments of tumor genetic material from a simple blood sample and this was the object of the other study, published in Gut – underlines Mazzaferro, who returned to the “World’s 2% Top Scientists”, the world ranking of scientists with the highest level of scientific productivity (2% of the best in the world) -. The data have shown us that even with this method it is possible to identify 90% of liver tumors sensitive to immunotherapy treatments, with undeniable advantages also for the patient who is subjected only to a blood sample”.
Radio-embolization to enhance the effect
Anti-PD1 immunotherapy drugs have been in clinical practice for years now for the treatment of melanoma, lung cancer and other solid tumors, but in the case of the liver they have variable and unpredictable efficacy. “The therapy enhances the body’s immune capacity and causes an important number of immunocompetent cells to converge on the tumor site, capable of recognizing and destroying oncogenic cells – explains Sherrie Bhoori, specialist in gastroenterology and hepatology of general surgery with an oncological focus 1 of the INT -. However, we know that only 20% of patients respond to this therapy, and at the moment the mechanisms that determine its sensitivity are not known. For this reason, we have now entered another phase of study, that is, the one that will allow us to identify patients who will be able to benefit from immunotherapy drugs and therefore be candidates for other more radical treatments, such as liver transplantation”. However, immunotherapy is not the only path that researchers are currently following. Another recent work published in Gut, curated by Licia Rivoltini of the INT immunotherapy unit, demonstrated the possibility of enhancing the immunological effect of anti-PD1 drugs with a pre-treatment. «Physical treatments such as radio-embolization can “prepare the ground” for the actual therapy – clarifies Mazzaferro, who coordinated the study -. In practice, they stimulate the production of specific tumor antigens, capable of activating groups of immunocompetent cells against the tumor, which will then be enhanced by immunotherapeutic drugs”.
The guidelines change
These studies not only broaden the range of therapeutic solutions for the treatment of liver cancer, currently the fifth most frequent cause of death from cancer worldwide, but can change the strategic approach to the treatment of this type of tumour. “Further research will be needed to obtain increasingly personalized therapies – concludes Bhoori, but the decision of the European Society for Organ Transplantation (ESOT) is significant: having examined the results of scientific works, the inclusion of neo-adjuvant immunotherapy was approved in the next European guidelines. This therapeutic approach therefore becomes one of the possible strategies to be adopted in selected cases, in particular when the so-called molecular signature is present”.
December 5, 2022 (change December 5, 2022 | 1:28 pm)
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