Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of imp...Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.展开更多
Immune therapy is a new avenue in the treatment of multiple myeloma(MM).The naked anti-38 antibodies daratumumab and isatuximab are already used in frontline therapy after excellent results have been achieved in relap...Immune therapy is a new avenue in the treatment of multiple myeloma(MM).The naked anti-38 antibodies daratumumab and isatuximab are already used in frontline therapy after excellent results have been achieved in relapsed/refractory MM(RRMM).The second step was the development of immune therapies targeting B cell maturation antigen(BCMA).Genetically modified autologous chimeric antigen receptor(CAR)-T cell therapy BCMA-directed were initially tested in heavily pretreated patients with RRMM exposed to the 3 main therapeutic classes,immunomodulatory drugs(iMiDs),proteasome inhibitors,and anti-CD38 antibodies(triple-class exposed).Efficacy results were unprecedented in this context and Idecabtagene vicleucel(ide-cel or Abecma)was the first BCMA-directed CAR-T cell therapy approved in MM by both Federal Drug Administration(FDA)and European Medicines Agency(EMA).展开更多
LncRNAs are defined as RNA transcripts greater than 200 nucleotides in length that have no or limited protein-coding potential.Basal expression of lncRNAs appeared important for various homeostatic processes,like gene...LncRNAs are defined as RNA transcripts greater than 200 nucleotides in length that have no or limited protein-coding potential.Basal expression of lncRNAs appeared important for various homeostatic processes,like gene imprinting cell differentiation and organogenesis.Moreover,it has been demonstrated that lncRNAs play an important role in tumorigenesis and metastasis.Some lncRNAs were stably detected in exosomes,which are widely found in body fluids.Several studies validated the use of exosomal lncRNAs as minimally invasive diagnostic and prognostic markers in several types of cancers.In addition,exosomal lncRNAs have been associated with drug resistance of tumor cells,suggesting a clinical application in cancer-targeted therapy.Despite the recent increase of studies on exosomal lncRNAs,their clinical significance in cancer diagnosis,prognosis and treatment needs to be fully explored.The methodologies for their detection with high purity and accuracy must be also improved in order to implement their use in clinical routine.This review aims to summarize the main recent technologies available for the isolation of exosomal lncRNAs,their status as a liquid biopsy as well as their future perspectives.展开更多
Hepatocellular carcinoma(HCC)is a severe liver cancer that complicates underlying severe liver disease.For a long time,palliative treatment of unresectable HCC was loco-regional and based on tumor arterial hypervascul...Hepatocellular carcinoma(HCC)is a severe liver cancer that complicates underlying severe liver disease.For a long time,palliative treatment of unresectable HCC was loco-regional and based on tumor arterial hypervascularization and intra-tumor retention of Lipiodol when injected intra-arterially.In 1995,it was demonstrated that transarterial chemoembolization(TACE)reduced tumor growth and size,but did not significantly improve survival,because any benefit was offset by worsened liver function(1).Despite the failure to demonstrate improved survival,TACE remained the most commonly used palliative treatment worldwide for many years.In 2002,two RCTs demonstrated the efficacy of TACE,but only in highly selected patients(2).The good indications for TACE were limited to certain intermediate stage HCC,PS 0(or possibly 1),with preserved liver function(Child-Pugh A without ascites),without vascular invasion,and had to be carried out in a selective manner to minimize the ischemic insult to non-tumoral tissue(3,4).In scores evaluating survival after a first TACE,the parameters linked to liver toxicity were more important than tumor response!In a recent comparison of TACE with lenvatinib,TACE but not lenvatinib was responsible for a severe decrease in the liver function(evaluating by the ALBI score)from baseline,and this acute deterioration persisted in the chronic period(5).The price to pay for the efficacy of TACE is thus liver function.展开更多
文摘Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.
文摘Immune therapy is a new avenue in the treatment of multiple myeloma(MM).The naked anti-38 antibodies daratumumab and isatuximab are already used in frontline therapy after excellent results have been achieved in relapsed/refractory MM(RRMM).The second step was the development of immune therapies targeting B cell maturation antigen(BCMA).Genetically modified autologous chimeric antigen receptor(CAR)-T cell therapy BCMA-directed were initially tested in heavily pretreated patients with RRMM exposed to the 3 main therapeutic classes,immunomodulatory drugs(iMiDs),proteasome inhibitors,and anti-CD38 antibodies(triple-class exposed).Efficacy results were unprecedented in this context and Idecabtagene vicleucel(ide-cel or Abecma)was the first BCMA-directed CAR-T cell therapy approved in MM by both Federal Drug Administration(FDA)and European Medicines Agency(EMA).
文摘LncRNAs are defined as RNA transcripts greater than 200 nucleotides in length that have no or limited protein-coding potential.Basal expression of lncRNAs appeared important for various homeostatic processes,like gene imprinting cell differentiation and organogenesis.Moreover,it has been demonstrated that lncRNAs play an important role in tumorigenesis and metastasis.Some lncRNAs were stably detected in exosomes,which are widely found in body fluids.Several studies validated the use of exosomal lncRNAs as minimally invasive diagnostic and prognostic markers in several types of cancers.In addition,exosomal lncRNAs have been associated with drug resistance of tumor cells,suggesting a clinical application in cancer-targeted therapy.Despite the recent increase of studies on exosomal lncRNAs,their clinical significance in cancer diagnosis,prognosis and treatment needs to be fully explored.The methodologies for their detection with high purity and accuracy must be also improved in order to implement their use in clinical routine.This review aims to summarize the main recent technologies available for the isolation of exosomal lncRNAs,their status as a liquid biopsy as well as their future perspectives.
文摘Hepatocellular carcinoma(HCC)is a severe liver cancer that complicates underlying severe liver disease.For a long time,palliative treatment of unresectable HCC was loco-regional and based on tumor arterial hypervascularization and intra-tumor retention of Lipiodol when injected intra-arterially.In 1995,it was demonstrated that transarterial chemoembolization(TACE)reduced tumor growth and size,but did not significantly improve survival,because any benefit was offset by worsened liver function(1).Despite the failure to demonstrate improved survival,TACE remained the most commonly used palliative treatment worldwide for many years.In 2002,two RCTs demonstrated the efficacy of TACE,but only in highly selected patients(2).The good indications for TACE were limited to certain intermediate stage HCC,PS 0(or possibly 1),with preserved liver function(Child-Pugh A without ascites),without vascular invasion,and had to be carried out in a selective manner to minimize the ischemic insult to non-tumoral tissue(3,4).In scores evaluating survival after a first TACE,the parameters linked to liver toxicity were more important than tumor response!In a recent comparison of TACE with lenvatinib,TACE but not lenvatinib was responsible for a severe decrease in the liver function(evaluating by the ALBI score)from baseline,and this acute deterioration persisted in the chronic period(5).The price to pay for the efficacy of TACE is thus liver function.
