TGF-β as Predictive Marker and Pharmacological Target in Lung Cancer Approach

SIMPLE SUMMARY: Lung cancer (LC) represents the leading cause of cancer incidence and mortality worldwide. LC is a lung tumor associated with genetic mutations and environmental (tobacco smoking) or pathological conditions, with poor prognosis and a difficult pharmacological approach. TGF-β is a molecule that regulates different biological processes at a pulmonary level, and its alteration has been associated with LC development and metastasis. Despite advancements in knowledge of the molecular mechanisms involved in LC, this tumor is still characterized by an unfavorable prognosis and current therapeutic options are unsatisfactory. Some studies have demonstrated that TGF-β overexpression could be considered a potential predictive marker in LC prognosis, and TGF-β inhibition has been shown to prevent LC metastasis. Moreover, TGF-β inhibitors could be used in combination with chemo- and immunotherapy, thereby improving patient survival. Overall, targeting TGF-β may be a valid possibility to fight LC, and is a novel and effective strategy against this aggressive cancer. ABSTRACT: Lung cancer (LC) represents the leading cause of cancer incidence and mortality worldwide. LC onset is strongly related to genetic mutations and environmental interactions, such as tobacco smoking, or pathological conditions, such as chronic inflammation. Despite advancement in knowledge of the molecular mechanisms involved in LC, this tumor is still characterized by an unfavorable prognosis, and the current therapeutic options are unsatisfactory. TGF-β is a cytokine that regulates different biological processes, particularly at the pulmonary level, and its alteration has been demonstrated to be associated with LC progression. Moreover, TGF-β is involved in promoting invasiveness and metastasis, via epithelial to mesenchymal transition (EMT) induction, where TGF-β is the major driver. Thus, a TGF-β-EMT signature may be considered a potential predictive marker in LC prognosis, and TGF-β-EMT inhibition has been demonstrated to prevent metastasis in various animal models. Concerning a LC therapeutic approach, some TGF-β and TGF-β-EMT inhibitors could be used in combination with chemo- and immunotherapy without major side effects, thereby improving cancer therapy. Overall, targeting TGF-β may be a valid possibility to fight LC, both in improving LC prognosis and cancer therapy, via a novel approach that could open up new effective strategies against this aggressive cancer.