The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research ...The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.展开更多
Using pseudorabies virus Ea strain as material,we inserted LacZ gene expression cassette into gE gene.After blue plaque and plaque purification,a recombinant virus PRVEa TK+-/gE+-/LacZ++ generated.Utilizing EcoR I sit...Using pseudorabies virus Ea strain as material,we inserted LacZ gene expression cassette into gE gene.After blue plaque and plaque purification,a recombinant virus PRVEa TK+-/gE+-/LacZ++ generated.Utilizing EcoR I site in LacZ gene, digested PRVEa TK+-/gE+-/LacZ++ genome DNA was cotransfected into PK-15 cells with plasmid pFBBS,then PRVEa TK+-/gE+-/gp63+- generated after plaque purification.Four pairs of primers amplification demonstrated the virus was pure TK+-/gE+-/gp63+- mutant virus.PCR product sequence indicates there were 205bp deletion in TK gene;1247bp deletion in gE,gp63 and intergenic region of PRVEa TK+-/gE+-/gp63+- mutant virus genome DNA.Inoculation to Balb/C mice with PRVEa TK+-/gE+-/gp63+- indicates the virulence is reduced greatly.展开更多
基金supported by the Department of Biotechnology(DBT),Government of India(BT/556/NE/U-Excel/).
文摘The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
文摘Using pseudorabies virus Ea strain as material,we inserted LacZ gene expression cassette into gE gene.After blue plaque and plaque purification,a recombinant virus PRVEa TK+-/gE+-/LacZ++ generated.Utilizing EcoR I site in LacZ gene, digested PRVEa TK+-/gE+-/LacZ++ genome DNA was cotransfected into PK-15 cells with plasmid pFBBS,then PRVEa TK+-/gE+-/gp63+- generated after plaque purification.Four pairs of primers amplification demonstrated the virus was pure TK+-/gE+-/gp63+- mutant virus.PCR product sequence indicates there were 205bp deletion in TK gene;1247bp deletion in gE,gp63 and intergenic region of PRVEa TK+-/gE+-/gp63+- mutant virus genome DNA.Inoculation to Balb/C mice with PRVEa TK+-/gE+-/gp63+- indicates the virulence is reduced greatly.
