Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) identifies a specific lung disorder characterized by chronic, progressive fibrosing interstitial pneumonia of unknown etiology, which lacks effective treatment. According to the current pathogenic perspective, the aberrant proliferative events in IPF resemble those occurring during malignant transformation. Main body:Receptor tyrosine kinases (RTK) are known to be key players in cancer onset and progression. It has been demonstrated that RTK expression is sometimes also altered and even druggable in IPF. One example of an RTK-the MET proto-oncogene-is a key regulator of invasive growth. This physiological genetic program supports embryonic development and post-natal organ regeneration, as well as cooperating in the evolution of cancer metastasis when aberrantly activated. Growing evidence sustains that MET activation may collaborate in maintaining tissue plasticity and the regenerative potential that characterizes IPF. Conclusion:The present work aims to elucidate-by applying the logic of simplicity-the bio-molecular mechanisms involved in MET activation in IPF. This clarification is crucial to accurately design MET blockade strategies within a fully personalized approach to IPF.

MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin

“…Thus, our data strongly suggest that the non-catalytic SEMA domain is involved in neoplastic invasiveness, although no clear mechanistic explanation is given by only biological characterization of SEMA mutants. Notably, we further demonstrated that the occurrence of SEMA mutations is associated with aggressive and radioresistant brain metastasis from known primary (lung) ( Stella et al, 2016a , Stella et al, 2016b ) thus confirming the tumorigenic potential of SEMA-mutated cells. Those findings allowed us to hypothesize that changes affecting the SEMA domain coding sequence may be reflected in structural alteration of the extracellular portion of the MET receptor.…”

“…Notably, MET genetic alteration is being targeted and in some instances quite successfully by various MET inhibitors. Several reports are already available on these topic (for a review see Comoglio et al, 2008 ; Gherardi et al, 2012 ; Stella et al, 2016b ; Ma, 2017 ). Details on anti-MET agents which already landed the clinical arena are summarized in Table 1 .…”

Enabling Precision Cardiology Through Multiscale Biology and Systems Medicine

“…The term is currently most often associated with the field of oncology, where rapid disease progression in cancer results from a series of somatic mutational events, which often clearly define a before- and after-disease state. This dichotomy provides a clear avenue to target treatments to an individual patient’s mutational profile 26 , 27 , 28 , 29 . The term is also used to define the application of genomic profiling and pharmacogenomics in a public health setting 30 , 31 , 32 , 33 .…”

Erratum to: Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

“…In the original version of this article [ 1 ], published on 2 September 2016, the name of author ‘Alice Balderacchi’ was wrongly displayed. In this Erratum the incorrect name and correct name are shown.…”