Pubblicazioni

Autori:

Merz, V; Gaule, M; Zecchetto, C; Cavaliere, A; Casalino, S; Pesoni, C; Contarelli, S; Sabbadini, F; Bertolini, M; Mangiameli, D; Milella, M; Fedele, V; Melisi, D

Titolo:

Targeting KRAS: The Elephant in the Room of Epithelial Cancers

Anno:

2021

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Referee:

No

Nome rivista:

FRONTIERS IN ONCOLOGY

ISSN Rivista:

2234-943X

N° Volume:

11

Intervallo pagine:

1-16

Parole chiave:

KRAS; NSCLC; pancreatic cancer; colon cancer; G12C mutation

Breve descrizione dei contenuti:

Mutations of the proto-oncogene KRAS are the most frequent gain-of-function alterations found in cancer. KRAS is mutated in about 30% of all human tumors, but it could reach more than 90% in certain cancer types such as pancreatic adenocarcinoma. Although historically considered to be undruggable, a particular KRAS mutation, the G12C variant, has recently emerged as an actionable alteration especially in non-small cell lung cancer (NSCLC). KRAS(G12C) and pan-KRAS inhibitors are being tested in clinical trials and have recently shown promising activity. Due to the difficulties in direct targeting of KRAS, other approaches are being explored. The inhibition of target upstream activators or downstream effectors of KRAS pathway has shown to be moderately effective given the evidence of emerging mechanisms of resistance. Various synthetic lethal partners of KRAS have recently being identified and the inhibition of some of those might prove to be successful in the future. The study of escape mechanisms to KRAS inhibition could support the utility of combination strategies in overcoming intrinsic and adaptive resistance and enhancing clinical benefit of KRAS(G12C) inhibitors. Considering the role of the microenvironment in influencing tumor initiation and promotion, the immune tumor niche of KRAS mutant tumors has been deeply explored and characterized for its unique immunosuppressive skewing. However, a number of aspects remains to be fully understood, and modulating this tumor niche might revert the immunoresistance of KRAS mutant tumors. Synergistic associations of KRAS(G12C) and immune checkpoint inhibitors are being tested.

Id prodotto:

121334

Handle IRIS:

11562/1044674

ultima modifica:

15 novembre 2022

Citazione bibliografica:

Merz, V; Gaule, M; Zecchetto, C; Cavaliere, A; Casalino, S; Pesoni, C; Contarelli, S; Sabbadini, F; Bertolini, M; Mangiameli, D; Milella, M; Fedele, V; Melisi, D, Targeting KRAS: The Elephant in the Room of Epithelial Cancers «FRONTIERS IN ONCOLOGY» , vol. 11 , 2021 , pp. 1-16

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