The Genes–Stemness–Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints

Abstract

MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets.

Dual‑regulated oncolytic adenovirus carrying ERCC1‑siRNA gene possesses potent antitumor effect on ovarian cancer cells

“…As demonstrated in Fig. 2D , the recombinant adenovirus caused a significant increase in cell mortality from MOI 5 (~47.87% for 48 h and 62.49% for 72 h) to MOI 500 [~94.03% for 48 h and 95.43% for 72 h; one-way ANOVA; 48 h: F ( 9 , 20 ) =362.834; P<0.001; vs. the control group, LOG ( 5 ): P<0.001; LOG ( 10 ): P<0.001; LOG (50): P<0.001; LOG (100): P<0.001; LOG (500): P<0.001; 72 h: F ( 9 , 20 ) =313.047; P<0.001; vs. the control group, LOG ( 5 ): P<0.001; LOG ( 10 ): P<0.001; LOG (50): P<0.001; LOG (100): P<0.001; LOG (500): P<0.001].…”

“…Furthermore, it is highly desirable to develop a repertoire of vectors that can exploit microenvironmental constraints specific to tumor growth, in addition to cell intrinsic gene expression profiles or genetic alterations. Hypoxia, characterized by a reduction in O 2 partial pressure, is a key element of the tumor microenvironment, commonly found in most solid tumors irrespective of their origin, location, or genetic makeup ( 20 , 21 ). Hypoxia plays a pivotal role in conferring resistance of cancer cells to radiotherapy and chemotherapy, promoting the selection of more aggressive tumor clones and facilitating metastasis predisposition ( 22 , 23 ).…”

“…Thus, there is a critical need to devise innovative therapeutic strategies that can specifically target hypoxic regions within tumors. Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that governs cellular responses to hypoxia by binding to a hypoxia-response element (HRE) present within target genes ( 20 , 21 ). The HIF/HRE regulatory system becomes active under hypoxia or in response to genetic alterations during cell transformation.…”