FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200191138> ?p ?o ?g. }

• W4200191138 endingPage "100796" @default.
• W4200191138 startingPage "100796" @default.
• W4200191138 abstract "Driver mutations promote initiation and progression of cancer. Pharmacological treatment can inhibit the action of the mutant protein; however, drug resistance almost invariably emerges. Multiple studies revealed that cancer drug resistance is based upon a plethora of distinct mechanisms. Drug resistance mutations can occur in the same protein or in different proteins; as well as in the same pathway or in parallel pathways, bypassing the intercepted signaling. The dilemma that the clinical oncologist is facing is that not all the genomic alterations as well as alterations in the tumor microenvironment that facilitate cancer cell proliferation are known, and neither are the alterations that are likely to promote metastasis. For example, the common KRasG12C driver mutation emerges in different cancers. Most occur in NSCLC, but some occur, albeit to a lower extent, in colorectal cancer and pancreatic ductal carcinoma. The responses to KRasG12C inhibitors are variable and fall into three categories, (i) new point mutations in KRas, or multiple copies of KRAS G12C which lead to higher expression level of the mutant protein; (ii) mutations in genes other than KRAS; (iii) original cancer transitioning to other cancer(s). Resistance to adagrasib, an experimental antitumor agent exerting its cytotoxic effect as a covalent inhibitor of the G12C KRas, indicated that half of the cases present multiple KRas mutations as well as allele amplification. Redundant or parallel pathways included MET amplification; emerging driver mutations in NRAS, BRAF, MAP2K1, and RET; gene fusion events in ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN tumor suppressors. In the current review we discuss the molecular mechanisms underlying drug resistance while focusing on those emerging to common targeted cancer drivers. We also address questions of why cancers with a common driver mutation are unlikely to evolve a common drug resistance mechanism, and whether one can predict the likely mechanisms that the tumor cell may develop. These vastly important and tantalizing questions in drug discovery, and broadly in precision medicine, are the focus of our present review. We end with our perspective, which calls for target combinations to be selected and prioritized with the help of the emerging massive compute power which enables artificial intelligence, and the increased gathering of data to overcome its insatiable needs." @default.
• W4200191138 created "2021-12-31" @default.
• W4200191138 creator A5020262392 @default.
• W4200191138 creator A5025357844 @default.
• W4200191138 creator A5071084031 @default.
• W4200191138 date "2021-12-01" @default.
• W4200191138 modified "2023-10-12" @default.
• W4200191138 title "Anticancer drug resistance: An update and perspective" @default.
• W4200191138 cites W1132077651 @default.
• W4200191138 cites W1509500531 @default.
• W4200191138 cites W1545631393 @default.
• W4200191138 cites W1891916561 @default.
• W4200191138 cites W1912428744 @default.
• W4200191138 cites W1963579412 @default.
• W4200191138 cites W1964768580 @default.
• W4200191138 cites W1966803171 @default.
• W4200191138 cites W1970031133 @default.
• W4200191138 cites W1970527559 @default.
• W4200191138 cites W1975757940 @default.
• W4200191138 cites W1980209454 @default.
• W4200191138 cites W1980590401 @default.
• W4200191138 cites W1980937575 @default.
• W4200191138 cites W1982586481 @default.
• W4200191138 cites W1985689657 @default.
• W4200191138 cites W1987191607 @default.
• W4200191138 cites W1998971866 @default.
• W4200191138 cites W1999025555 @default.
• W4200191138 cites W1999275756 @default.
• W4200191138 cites W1999614615 @default.
• W4200191138 cites W2002937040 @default.
• W4200191138 cites W2004731962 @default.
• W4200191138 cites W2006434892 @default.
• W4200191138 cites W2009720434 @default.
• W4200191138 cites W2012952884 @default.
• W4200191138 cites W2015610139 @default.
• W4200191138 cites W2017081079 @default.
• W4200191138 cites W2021146265 @default.
• W4200191138 cites W2022609682 @default.
• W4200191138 cites W2024254552 @default.
• W4200191138 cites W2032860349 @default.
• W4200191138 cites W2041686632 @default.
• W4200191138 cites W2045713322 @default.
• W4200191138 cites W2051436758 @default.
• W4200191138 cites W2058965356 @default.
• W4200191138 cites W2061014293 @default.
• W4200191138 cites W2061932411 @default.
• W4200191138 cites W2063271214 @default.
• W4200191138 cites W2064442490 @default.
• W4200191138 cites W2064747770 @default.
• W4200191138 cites W2067826589 @default.
• W4200191138 cites W2070705072 @default.
• W4200191138 cites W2074930912 @default.
• W4200191138 cites W2077098920 @default.
• W4200191138 cites W2082426444 @default.
• W4200191138 cites W2084252867 @default.
• W4200191138 cites W2085456999 @default.
• W4200191138 cites W2090757807 @default.
• W4200191138 cites W2092647316 @default.
• W4200191138 cites W2097113581 @default.
• W4200191138 cites W2097946794 @default.
• W4200191138 cites W2099201986 @default.
• W4200191138 cites W2103980474 @default.
• W4200191138 cites W2106042158 @default.
• W4200191138 cites W2110444464 @default.
• W4200191138 cites W2111909718 @default.
• W4200191138 cites W2112655151 @default.
• W4200191138 cites W2115276344 @default.
• W4200191138 cites W2117247812 @default.
• W4200191138 cites W2121389354 @default.
• W4200191138 cites W2126275851 @default.
• W4200191138 cites W2126920848 @default.
• W4200191138 cites W2131487381 @default.
• W4200191138 cites W2133105825 @default.
• W4200191138 cites W2135184154 @default.
• W4200191138 cites W2138173746 @default.
• W4200191138 cites W2138297714 @default.
• W4200191138 cites W2141903666 @default.
• W4200191138 cites W2145324047 @default.
• W4200191138 cites W2145835533 @default.
• W4200191138 cites W2155311724 @default.
• W4200191138 cites W2155586760 @default.
• W4200191138 cites W2157824687 @default.
• W4200191138 cites W2158134441 @default.
• W4200191138 cites W2158910681 @default.
• W4200191138 cites W2163006881 @default.
• W4200191138 cites W2164242115 @default.
• W4200191138 cites W2169302611 @default.
• W4200191138 cites W2171490806 @default.
• W4200191138 cites W2187002261 @default.
• W4200191138 cites W2204695746 @default.
• W4200191138 cites W2231187859 @default.
• W4200191138 cites W2260312731 @default.
• W4200191138 cites W2260715119 @default.
• W4200191138 cites W2272802268 @default.
• W4200191138 cites W2287368907 @default.
• W4200191138 cites W2297701691 @default.
• W4200191138 cites W2298433762 @default.
• W4200191138 cites W2298480233 @default.

• next