OBJECTIVE The aim of this study was to investigate mRNA expression of tyrosine-kinase receptors （TRKs） and neurotrophins （NTs） in human neuroblastomas. METHODS Expression of TrkA, TrkB, TrkC and BDNF was quantitat...OBJECTIVE The aim of this study was to investigate mRNA expression of tyrosine-kinase receptors （TRKs） and neurotrophins （NTs） in human neuroblastomas. METHODS Expression of TrkA, TrkB, TrkC and BDNF was quantitatively examined by reverse transcription-polymerase chain reaction （RT-PCR） in 27 cases of neuroblastomas. RESULTS The high and total rates of TrkA were expressed in significantly more tumors in a lower-stage group compared to a higher-stage group （P〈0.05） and the high level of TrkA expression was correlated positively with the 2-year cumulative-survival rate of the patients （P〈 0.01）. The high and total rates of TrkB were expressed in significantly more tumors in a higher-stage group compared to a lower-stage group （P〈0.05）. All 3 rates of BDNF expression between the 2 groups showed no statistical difference （P〉0.05）, but the co-expression ratio of TrkB and BDNF showed a remarkable significance in the higher-stage group more than in the lower-stage group （P〈0.05）. TrkC expression was usually accompanied by TrkA expression, but there was only a non-significant trend between TrkC expression and TrkA expression. CONCLUSION RT-PCR for mRNA expression of TRKs and NTs has important clinical significance relating to the tumor stage and outcome for patients with neuroblastomas.展开更多
This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature An...This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.展开更多
Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represent...Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual “scenario” of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.展开更多
A selective and sensitive competitive enzyme-linked immunosorbent assay(ELISA) method was developed and validated for the quantification of erlotinib in 50 mL of samples of human serum. Anti-erlotinib serum was obtain...A selective and sensitive competitive enzyme-linked immunosorbent assay(ELISA) method was developed and validated for the quantification of erlotinib in 50 mL of samples of human serum. Anti-erlotinib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and 3,4-bis(2-methoxyethoxy)benzoic acid using the N-succinimidyl ester method. Enzyme labeling of erlotinib with horseradish peroxidase was similarly performed using 3,4-bis(2-methoxyethoxy)benzoic acid. A simple competitive ELISA for erlotinib was developed using the principle of direct competition between erlotinib and the enzyme marker for anti-erlotinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Serum erlotinib concentrations lower than 40 ng/mL were reproducibly measurable using the ELISA. This ELISA was specific to erlotinib and showed very slight cross-reactivity(6.7%) with a major metabolite, O-desmethyl erlotinib. Using this assay, drug levels were easily measured in the blood of mice after oral administration of erlotinib at a single dose of 30 mg/kg. ELISA should be used as a valuable tool for therapeutic drug monitoring and in pharmacokinetic studies of erlotinib.展开更多
Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodial...Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.展开更多
We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumo...We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.展开更多
Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug ...Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.展开更多
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within th...Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.展开更多
Introduction:Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic agents.Here,we present the first case of tyrosine-kinase i...Introduction:Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic agents.Here,we present the first case of tyrosine-kinase inhibitor-related external auditory canal(EAC)osteonecrosis as well as two cases related to anti-resorptive therapies.Methods:A retrospective case series.Results:Case one:an 84-year-old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally.She had a history of osteoporosis treated with denosumab and risedronic acid.She successfully underwent left EAC reconstruction using an inferiorly-based pedicle periosteal flap while the right ear canal was managed conservatively.Case two:a 69-year-old male presented with osteonecrosis of the right EAC.He had a history of osteoporosis treated with alendronic acid and zoledronic acid.His osteonecrosis is conservatively managed with local debridement and antibiotic application.Case three:a 60-year-old male presented with osteonecrosis of the right inferior EAC.He had a history of chronic myelogenous leukemia treated with a tyrosine-kinase inhibitor,imatinib.After failing conservative therapy,he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his symptoms.Conclusion:Anti-resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis.When a local debridement and antibiotic therapy fail,definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.展开更多
Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor ge...Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor.This paved the way to the introduction of imatinib and other tyrosine-kinase inhibitors(TKIs),which terrifically revolutionized the prognosis of GIST patients.Currently,it is well established that tumor mutational status is the main player in clinical outcome;however,with the research advances,it has been slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all the GIST subtypes.For this reason,in the era of tailored/personalized medicine,each GIST patient should be considered individually and genetic consult should be the first step to take in consideration in the therapeutic decision making process.展开更多
基金This work was supported by the National Natural Science Foundation of China （No.39470739）.
文摘OBJECTIVE The aim of this study was to investigate mRNA expression of tyrosine-kinase receptors （TRKs） and neurotrophins （NTs） in human neuroblastomas. METHODS Expression of TrkA, TrkB, TrkC and BDNF was quantitatively examined by reverse transcription-polymerase chain reaction （RT-PCR） in 27 cases of neuroblastomas. RESULTS The high and total rates of TrkA were expressed in significantly more tumors in a lower-stage group compared to a higher-stage group （P〈0.05） and the high level of TrkA expression was correlated positively with the 2-year cumulative-survival rate of the patients （P〈 0.01）. The high and total rates of TrkB were expressed in significantly more tumors in a higher-stage group compared to a lower-stage group （P〈0.05）. All 3 rates of BDNF expression between the 2 groups showed no statistical difference （P〉0.05）, but the co-expression ratio of TrkB and BDNF showed a remarkable significance in the higher-stage group more than in the lower-stage group （P〈0.05）. TrkC expression was usually accompanied by TrkA expression, but there was only a non-significant trend between TrkC expression and TrkA expression. CONCLUSION RT-PCR for mRNA expression of TRKs and NTs has important clinical significance relating to the tumor stage and outcome for patients with neuroblastomas.
文摘This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.
文摘Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual “scenario” of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.
文摘A selective and sensitive competitive enzyme-linked immunosorbent assay(ELISA) method was developed and validated for the quantification of erlotinib in 50 mL of samples of human serum. Anti-erlotinib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and 3,4-bis(2-methoxyethoxy)benzoic acid using the N-succinimidyl ester method. Enzyme labeling of erlotinib with horseradish peroxidase was similarly performed using 3,4-bis(2-methoxyethoxy)benzoic acid. A simple competitive ELISA for erlotinib was developed using the principle of direct competition between erlotinib and the enzyme marker for anti-erlotinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Serum erlotinib concentrations lower than 40 ng/mL were reproducibly measurable using the ELISA. This ELISA was specific to erlotinib and showed very slight cross-reactivity(6.7%) with a major metabolite, O-desmethyl erlotinib. Using this assay, drug levels were easily measured in the blood of mice after oral administration of erlotinib at a single dose of 30 mg/kg. ELISA should be used as a valuable tool for therapeutic drug monitoring and in pharmacokinetic studies of erlotinib.
基金the Taipei Tzu Chi Hospital,Buddhist Tzu Chi Medical Foundation,No.TCRD-TPE-108-RT-4(3/3)and No.TCRD-TPE-109-59.
文摘Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.
文摘We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.
文摘Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.
文摘Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.
文摘Introduction:Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic agents.Here,we present the first case of tyrosine-kinase inhibitor-related external auditory canal(EAC)osteonecrosis as well as two cases related to anti-resorptive therapies.Methods:A retrospective case series.Results:Case one:an 84-year-old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally.She had a history of osteoporosis treated with denosumab and risedronic acid.She successfully underwent left EAC reconstruction using an inferiorly-based pedicle periosteal flap while the right ear canal was managed conservatively.Case two:a 69-year-old male presented with osteonecrosis of the right EAC.He had a history of osteoporosis treated with alendronic acid and zoledronic acid.His osteonecrosis is conservatively managed with local debridement and antibiotic application.Case three:a 60-year-old male presented with osteonecrosis of the right inferior EAC.He had a history of chronic myelogenous leukemia treated with a tyrosine-kinase inhibitor,imatinib.After failing conservative therapy,he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his symptoms.Conclusion:Anti-resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis.When a local debridement and antibiotic therapy fail,definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.
文摘Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor.This paved the way to the introduction of imatinib and other tyrosine-kinase inhibitors(TKIs),which terrifically revolutionized the prognosis of GIST patients.Currently,it is well established that tumor mutational status is the main player in clinical outcome;however,with the research advances,it has been slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all the GIST subtypes.For this reason,in the era of tailored/personalized medicine,each GIST patient should be considered individually and genetic consult should be the first step to take in consideration in the therapeutic decision making process.
