ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for response out of >500 occurrences
343831 occurrences (No.54 in the rank) during 5 years in the PubMed. [cache]
288) The findings support further investigations into basic mechanisms by which complete lack of TP53 function regulates anticancer activity of eribulin and the potential utility of TP53 null phenotypes distinct from TP53 missense mutations as a biomarker of response in patients with lung cancer.
--- ABSTRACT ---
PMID:34031188 DOI:10.1124/molpharm.121.000254
2021 Molecular pharmacology
* TP53 Null Mutations Identify Lung Cancer Cell Lines with Highest Sensitivity to the Nontaxane Microtubule Inhibitor Eribulin.
- The nontaxane microtubule inhibitor eribulin is an approved therapeutic for metastatic breast cancer and liposarcoma. Eribulin was previously tested in unselected patients with lung cancer and yielded a modest objective response rate of ∼5%-12%. Because lung cancers represent diverse histologies and driving oncogenic mutations, we postulated that eribulin may exhibit properties of a precision oncology agent with a previously undefined specificity for a molecularly distinct subset of lung cancers. Herein, we screened a panel of 44 non-small cell and small-cell lung cancer cell lines for in vitro growth sensitivity to eribulin. The results revealed a greater than 15,000-fold range in eribulin sensitivity (IC50 = 0.005-89 nM) among the cell lines that was not correlated with their sensitivity to the taxane-based inhibitor paclitaxel. The quartile of cell lines exhibiting the lowest eribulin IC50 values was not enriched for specific histologies, epithelial-mesenchymal differentiation, or specific oncogene drivers but was significantly enriched for nonsense/frameshift TP53 mutations and low-TP53 mRNA but not missense TP53 mutations. By comparison, the mutation status of cyclin-dependent kinase inhibitor 2A, STK11, and KEAP1 was not associated with eribulin sensitivity. Finally, the highest eribulin IC50 quartile (>1 nM) exhibited significantly elevated mRNA expression of the drug pump, ATP binding cassette B1, defined resistance mechanism to eribulin, and paclitaxel. The findings support further investigations into basic mechanisms by which complete lack of TP53 function regulates anticancer activity of eribulin and the potential utility of TP53 null phenotypes distinct from TP53 missense mutations as a biomarker of response in patients with lung cancer. SIGNIFICANCE STATEMENT: Distinct from precision oncology agents that are matched to cancers bearing oncogenically activated versions of their targets, microtubule inhibitors, such as eribulin, are deployed in an unselected manner. The results in this study demonstrate that lung cancer cell lines exhibiting the highest sensitivity to eribulin bear TP53 null phenotypes, supporting a rationale to consider the status of this tumor suppressor in the clinical setting.
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(1)170 to (11)5 rates (21)2 although (31)2 profiles
(2)56 *null* (12)5 with (22)2 are (32)2 regulator
(3)27 and (13)3 at (23)2 bias, (33)2 relationship
(4)21 of (14)3 bias (24)2 burden (34)2 surface
(5)20 in (15)3 genes (25)2 compared (35)2 theory
(6)11 was (16)3 the (26)2 curve (36)2 time
(7)8 that (17)3 through (27)2 during (37)2 when
(8)7 is (18)3 were (28)2 from
(9)5 by (19)2 (UPR) (29)2 observed
(10)5 rate (20)2 across (30)2 our

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--- WordNet output for response --- =>反応, 応答, 返答, 返報, 反響, 答唱句 Overview of noun response The noun response has 7 senses (first 5 from tagged texts) 1. (11) response -- (a result; "this situation developed in response to events in Africa") 2. (11) reaction, response -- (a bodily process occurring due to the effect of some antecedent stimulus or agent; "a bad reaction to the medicine"; "his responses have slowed with age") 3. (6) answer, reply, response -- (a statement (either spoken or written) that is made to reply to a question or request or criticism or accusation; "I waited several days for his answer"; "he wrote replies to several of his critics") 4. (4) reception, response -- (the manner in which something is greeted; "she did not expect the cold reception she received from her superiors") 5. (1) response -- (a phrase recited or sung by the congregation following a versicle by the priest or minister) 6. reply, response -- (the speech act of continuing a conversational exchange; "he growled his reply") 7. response -- (the manner in which an electrical or mechanical device responds to an input signal or a range of input signals) --- WordNet end ---