Background:Glecirasib,an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12(KRAS G12C),has exhibited clinical activity in non-small-cell lung cancer(NSCLC)and colorect...Background:Glecirasib,an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12(KRAS G12C),has exhibited clinical activity in non-small-cell lung cancer(NSCLC)and colorectal cancer(CRC).Here,we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma(PDAC)and other solid tumors(excluding NSCLC and CRC)that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited.Methods:We conducted and analyzed two open-label,phase I/II trials in adult patients with KRAS G12C mutant solid tumors,in which glecirasib was administered orally.The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment.We performed a pooled analysis of all patients,excluding NSCLC and CRC,from both trials.The primary end-point in the pooled population was objective response rate(ORR).Efficacy and safety were assessed in patients who received at least one dose of glecirasib.Results:As of June 30,2024,the pooled analysis included 54 patients who were treated with glecirasib:32 PDACs,8 biliary tract cancers(BTCs),4 small intestinal cancers,3 gastric cancers,2 appendiceal cancers,and 5 other tumors.At baseline,24 received≥two prior lines of systemic therapy.Of the 53 efficacyevaluable patients,the confirmed ORR was 50.9%(95%confidence interval[CI],36.8%-64.9%),with an ORR of 46.9%(95%CI,29.1%-65.3%)in PDAC patients.Among other solid tumors,ORR was 71.4%(5/7)in BTC,100%(4/4)in small intestinal cancer,and 66.7%(2/3)in gastric cancer.Median progression-free survival and median overall survival were 6.9 and 10.8 months,respectively,in the overall population,and 5.5 and 10.8 months,respectively,in patients with PDAC.Treatment-related adverse events(TRAEs)of any grade occurred in 94.4%patients,with grade≥3 TRAEs in 27.8%.No fatal TRAEs or TRAEs leading to treatment discontinuation occurred.Conclusions:Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors(beyond NSCLC and CRC),warranting further expedited clinical development in this patient population.Trial registration:ClinicalTrials.gov identifier:NCT05009329 and NCT05002270.展开更多
Together with pathogenic microbes and herbivorous insects,parasitic plants are emerging as aggressive threats on agriculture worldwide.Among them,Cuscuta(dodder),a stem holoparasite,extracts nutrients and water from h...Together with pathogenic microbes and herbivorous insects,parasitic plants are emerging as aggressive threats on agriculture worldwide.Among them,Cuscuta(dodder),a stem holoparasite,extracts nutrients and water from host plants through phloem feeding.Dodder is parasitic on a very wide variety of plants,including a number of important agricultural and horticultural crops such as alfalfa,clover,tomatoes,and potatoes.Dodder in-festations cause major economic concerns,including crop yield reduction and cost increase of crop harvesting.Understanding resistance mechanisms against dodder can provide potential so-lutions to effectively control dodder infestations.展开更多
Plants possess a remarkable capacity to perceive numerous environmental signals and to respond to their surroundings.Stimuli from pathogens,beneficial microbes,as well as chemicals and abiotic stress,can trigger estab...Plants possess a remarkable capacity to perceive numerous environmental signals and to respond to their surroundings.Stimuli from pathogens,beneficial microbes,as well as chemicals and abiotic stress,can trigger establishment of induced resistance in plants.Defense priming is an intrinsic part of induced resistance:plants take defensive measures while also prepare its immune system for a faster and/or stronger response against subsequent pathogen attacks.Various signals have been implicated to play a role in defense priming,including salicylic acid(SA),pipecolic acid(Pip),andβ-aminobutyric acid(BABA)(Figure 1).展开更多
Receptor-like kinases,representing the largest transmembrane receptor family in plants,contribute to different aspects of the plant life cycle.During the past decade,a number of studies have highlighted FERONIA(FER)as...Receptor-like kinases,representing the largest transmembrane receptor family in plants,contribute to different aspects of the plant life cycle.During the past decade,a number of studies have highlighted FERONIA(FER)as a versatile receptor playing important roles in plant growth and stress responses(Zhang et al.,2020).展开更多
文摘Background:Glecirasib,an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12(KRAS G12C),has exhibited clinical activity in non-small-cell lung cancer(NSCLC)and colorectal cancer(CRC).Here,we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma(PDAC)and other solid tumors(excluding NSCLC and CRC)that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited.Methods:We conducted and analyzed two open-label,phase I/II trials in adult patients with KRAS G12C mutant solid tumors,in which glecirasib was administered orally.The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment.We performed a pooled analysis of all patients,excluding NSCLC and CRC,from both trials.The primary end-point in the pooled population was objective response rate(ORR).Efficacy and safety were assessed in patients who received at least one dose of glecirasib.Results:As of June 30,2024,the pooled analysis included 54 patients who were treated with glecirasib:32 PDACs,8 biliary tract cancers(BTCs),4 small intestinal cancers,3 gastric cancers,2 appendiceal cancers,and 5 other tumors.At baseline,24 received≥two prior lines of systemic therapy.Of the 53 efficacyevaluable patients,the confirmed ORR was 50.9%(95%confidence interval[CI],36.8%-64.9%),with an ORR of 46.9%(95%CI,29.1%-65.3%)in PDAC patients.Among other solid tumors,ORR was 71.4%(5/7)in BTC,100%(4/4)in small intestinal cancer,and 66.7%(2/3)in gastric cancer.Median progression-free survival and median overall survival were 6.9 and 10.8 months,respectively,in the overall population,and 5.5 and 10.8 months,respectively,in patients with PDAC.Treatment-related adverse events(TRAEs)of any grade occurred in 94.4%patients,with grade≥3 TRAEs in 27.8%.No fatal TRAEs or TRAEs leading to treatment discontinuation occurred.Conclusions:Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors(beyond NSCLC and CRC),warranting further expedited clinical development in this patient population.Trial registration:ClinicalTrials.gov identifier:NCT05009329 and NCT05002270.
文摘Together with pathogenic microbes and herbivorous insects,parasitic plants are emerging as aggressive threats on agriculture worldwide.Among them,Cuscuta(dodder),a stem holoparasite,extracts nutrients and water from host plants through phloem feeding.Dodder is parasitic on a very wide variety of plants,including a number of important agricultural and horticultural crops such as alfalfa,clover,tomatoes,and potatoes.Dodder in-festations cause major economic concerns,including crop yield reduction and cost increase of crop harvesting.Understanding resistance mechanisms against dodder can provide potential so-lutions to effectively control dodder infestations.
文摘Plants possess a remarkable capacity to perceive numerous environmental signals and to respond to their surroundings.Stimuli from pathogens,beneficial microbes,as well as chemicals and abiotic stress,can trigger establishment of induced resistance in plants.Defense priming is an intrinsic part of induced resistance:plants take defensive measures while also prepare its immune system for a faster and/or stronger response against subsequent pathogen attacks.Various signals have been implicated to play a role in defense priming,including salicylic acid(SA),pipecolic acid(Pip),andβ-aminobutyric acid(BABA)(Figure 1).
文摘Receptor-like kinases,representing the largest transmembrane receptor family in plants,contribute to different aspects of the plant life cycle.During the past decade,a number of studies have highlighted FERONIA(FER)as a versatile receptor playing important roles in plant growth and stress responses(Zhang et al.,2020).
