Hepatocellular carcinoma (HCC) is one of the most common liver tumors, and its prevalence is increasing rapidly. It also presents a high frequency of relapse and risk of metastasis. A recent study, led by the research group \u201cTGF-beta and cancer\u201d of the Oncobell programme at the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr. Isabel Fabregat, highlights the need to address personalized therapies to efficiently treat patients, a practice that necessarily implies stratification based on the specific molecular characteristics of the tumor (the so-called biomarkers). This strategy will only become real if the great complexity of the molecular signaling pathways involved in cancer is described, an objective to which the last work of Fabregat\u2019s group contributes. The results of the study, which were obtained in collaboration with the group of Dr. Victoria Sanz-Moreno, from the Barts Cancer Institute (Cancer Research UK), have been published in the journal Cancer Letters. To obtain them, researchers have worked with hepatocarcinoma samples from patients treated at Bellvitge University Hospital.<\/p>\n
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Specifically, the work seeks to deepen the knowledge of two very important molecular signaling pathways in the liver and in cancer: the epidermal growth factor receptor (EGFR) and the transforming growth factor beta (TGF-\u03b2) pathways. The EGFR pathway was considered key in the design of new therapies aimed at fighting HCC, but clinical experience has shown that administering EGFR inhibitors does not always lead to therapeutic success. For example, monoclonal antibodies against EGFR (such as cetuximab), or inhibitors of EGFR activity (such as gefitinib or erlotinib), showed modest or no activity in patients with advanced HCC. This fact, of vital medical importance, led the researchers to rethink the real implication of this pathway in liver cancer and encouraged them to study the biochemical details that clarify its functioning. As in many other times, the complexity of these routes is responsible for unexpected and unwanted responses to treatments.<\/p>\n
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EGFR belongs to a family of receptors with essential functions in cell proliferation, survival, differentiation, adhesion and migration. Alterations in their activity have been implicated in the development and growth of many tumors. TGF-\u03b2 is known as a liver tumor suppressor, which inhibits proliferation and induces cell death. However, paradoxically, TGF-\u03b2 also modulates processes such as invasion, immune regulation and remodeling of the cellular microenvironment, which cancer cells can exploit to their advantage. In previous studies, the research group has already described the existence of an interrelation of the TGF-\u03b2 and EGFR pathways, which allows HCC cells to escape the suppressive actions induced by TGF-\u03b2.<\/p>\n
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For these reasons, the objective of the study was to understand how EGFR is regulated in HCC, and if it has a possible contribution to the pro-migratory and invasive effects driven by TGF-\u03b2. Surprisingly, results obtained show that the silencing of the EGF receptor facilitates the ability of TGF-\u03b2 to promote the migration of cancer cells. Using 2D\/3D cellular models, the team has shown that after the loss of EGFR, TGF-\u03b2 is more efficient in its pro-migratory and invasive effects. Specifically, an amoeboid-type migration is induced, which gives them a high metastatic capacity. This migration could contribute to the dissemination of tumor nodules, a situation that greatly hinders the surgical intervention of the diseased liver.<\/p>\n
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To correctly and effectively treat patients, it is necessary to fully understand the specific molecular characteristics of their cancer, such as the expression levels of TGFB1 and EGFR. The IDIBELL study shows that EGFR is frequently negatively regulated in patients with HCC, while TGF-\u03b2 is positively regulated. Moreover, low levels of EGFR combined with high levels of TGFB1 confer a poor prognosis for the patient. These results indicate that the large subset of HCC patients who have low levels of EGFR expression and high levels of TGFB1 would benefit from attacking the TGF-\u03b2 pathway by specific inhibitors of this cytokine, and in turn should not be treated with classic therapies directed against EGFR.<\/p>\n","protected":false},"excerpt":{"rendered":"
Results show that in order to treat patients efficiently, it is necessary to know the specific molecular characteristics of their cancer, such as TGF-\u03b2 and EGF receptor expression levels<\/p>\n","protected":false},"author":6,"featured_media":7301,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[180,215],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-15 18:38:02","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts\/5041"}],"collection":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/comments?post=5041"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts\/5041\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/media\/7301"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/media?parent=5041"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/categories?post=5041"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/tags?post=5041"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}