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@#Abstract: As potential immunomodulators, platinum-based drugs could trigger immunogenic cell death (ICD). Hence, combination of platinum-based chemotherapy and immunotherapy could have better synergistic anticancer effect. Pt(II)-based drugs are the most common chemotherapeutic agents in cancer treatment yet with limited clinical application due to their toxic side-effects and drug resistance. Pt(IV) complexes have been widely investigated in the past decades due to their kinetic inertness and unique mechanisms . This article summarizes the progress in the pharmacological activities and mechanisms of Pt(IV) antitumor complexes via introducing different immunomodulators into chemotherapeutic agents in literature over recent years and highlights the potential targets and molecular signaling pathways so as to provide some reference for further development and potential clinical application of platinum-based chemo-immunotherapeutic agents.
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Objective:To explore the differences in tumor-specific growth factors, cellular immune function and efficacy of olaparib and platinum-containing regimen for treatment of platinum-sensitive relapsed ovarian cancer patients with BRCA mutation.Methods:A retrospective cohort study was conducted. A total of 100 platinum-sensitive relapsed BRCA-mutant ovarian cancer patients in Baoding Second Central Hospital from September 2017 to March 2020 were retrospectively selected. The clinical data of the patients were analyzed, and they were divided into the olaparib group (treated with olaparib tablets) and the platinum-containing regimen group (treated with paclitaxel and platinum drugs for 6 cycles, followed by olaparib tablets maintenance therapy), with 50 patients in each group. The clinical efficacy, tumor specific growth factor [carbohydrate antigen (CA) 125, CA199, human epididymal protein 4 (HE4)] levels, cellular immune function-related indicators [T-cell subsets (proportions of CD3 + cells and CD4 + cells), CD4 + cells/CD8 + cells ratio (CD4 +/CD8 +)], and quality of life scores before treatment and after 2, 4 and 6 cycles of treatment of the two groups were compared, as well as the safety of the two groups. The data of three years of follow-up were obtained, Kaplan-Meier method was used to analyze the progression-free survival (PFS) of patients in the two groups, and log-rank test was used for comparison between groups. Results:The age of patients in the olaparib and platinum-containing regimen groups was (53±7) years old and (56±7) years old, respectively. The differences in compositions of patients with different age, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status score, primary tumor location, lesion size, pathological stage, pathological type, germline BRCA mutation, and previous chemotherapy response between the two groups were not statistically significant (all P > 0.05). The objective response rate (ORR) [58.0% (29/50) vs. 38.0% (19/50)] and disease control rate (DCR) [80.0% (40/50) vs. 56.0% (28/50)] of the olaparib group after treatment were higher than those of the platinum-containing regimen group, and the differences were statistically significant (both P < 0.05). Serum CA125, CA199 and HE4 levels were gradually decreased in both groups before treatment and after 2, 4 and 6 cycles of treatment (all P < 0.05); serum CA125, CA199 and HE4 levels in the olaparib group after 2, 4 and 6 cycles of treatment were lower than those in the platinum-containing regimen group, and the differences were statistically significant (all P < 0.05). The CD3 + cells ratio, CD4 + cell ratio and CD4 +/CD8 + in the olaparib group gradually increased before treatment and after 2, 4 and 6 cycles of treatment (all P < 0.05), while those in the platinum-containing regimen group all gradually decreased (all P < 0.05); the CD3 + cells ratio, CD4 + cells ratio and CD4 +/CD8 + in the olaparib group were higher than those in the platinum-containing regimen group after 2, 4 and 6 cycles of treatment, and the differences were statistically significant (all P < 0.05). The quality of life scores of both groups increased before treatment and after 2, 4 and 6 cycles of treatment (all P < 0.05), and the quality of life scores of the olaparib group were higher than those of the platinum-containing regimen group after 2, 4 and 6 cycles of treatment, and the differences were statistically significant (all P < 0.05). The incidence of nausea, fatigue and malaise, vomiting, anemia, and diarrhea at all levels in the olaparib group was lower than those in the platinum-containing regimen group (all P < 0.05). By follow-up for 3 years, there was no statistically significant difference in PFS between the olaparib group and the platinum-containing regimen group ( P > 0.05). Conclusions:The efficacy of olaparib treatment in platinum-sensitive relapsed ovarian cancer patients with BRCA mutation is superior to platinum-containing regimen, and it can increase the level of T cells, inhibit the expression of tumor-specific growth factors, improve the quality of life, and have a positive effect on improving the safety of treatment.
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OBJECTIVE To evaluate the cost-effectiveness of apatinib combined with adriamycin in the second-line chemotherapy of platinum-resistant recurrent ovarian cancer （OC） from the perspective of the health system in China. METHODS A three-state partitioned survival model was constructed based on the APPROVE clinical trial and related literature data， with a model simulation time frame of 10 years and a 4-week cycle， and both cost and utility values were discounted using a 5% discount rate. Cost and quality-adjusted life years （QALYs） were used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the cost-effectiveness of apatinib combined with adriamycin versus adriamycin chemotherapy in the second-line treatment of platinum-resistant recurrent OC. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS The results of base-case analysis indicated that compared with chemotherapy alone， ICER of patients receiving apatinib combined with adriamycin was 124 678.25 yuan/QALY， which was less than willingness-to-pay （WTP） threshold set in this study [3 times per capita gross domestic product （GDP） of China in 2022 （257 094 yuan）]. The results of scenario analysis showed that， with the extension of the simulation time limit， the ICER of apatinib combined with adriamycin was gradually reduced， and the decline was gradually reduced， but both were less than WTP threshold. The results of single factor sensitivity analysis showed that the factors that had the greatest impact on ICER were the utility value of progression， body surface area， discount rate，and the cost of best supportive treatment， etc. The results of probability sensitivity analysis showed that under WTP threshold set in this study， the economic probability of apatinib combined with adriamycin was about 99%. CONCLUSIONS From the perspective of China’s health system， using three times the per capita GDP in 2022 as the WTP threshold， the combination of apatinib and adriamycin is more cost-effective than adriamycin alone in second-line chemotherapy for platinum-resistant recurrent OC.
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ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.
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Ovarian cancer has become the most lethal gynecological tumor due to the difficulty in early diagnosis,the late stage when diagnosed and the high recurrence rate.Resistance to platinum-based anti-tumor chemotherapy drugs is an important reason for the poor prognosis of ovarian cancer.circular RNA(circRNA)is more stable than mRNA in cells due to its special structure,and it is involved in the regulation of the occurrence,development and chemotherapy resistance of a variety of tumors.circRNA can be used as a competing endogenous RNA(ceRNA)of miRNA to bind to proteins,and regulates the phenotypic polarization of macrophages,it can also be used as an exosomal circRNA to regulate the sensitivity of platinum resistance in ovarian cancer.circRNA is expected to be a new marker of platinum resistance and a new target for the treatment of platinum resistance.In order to further explore the relationship between circRNA and platinum resistance in ovarian cancer,this article summarizes the recent literature related to circRNA and platinum resistance in ovarian cancer.
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Platinum-based nanoplatforms can enhance the absorption of X-ray due to the presence of high atomic number element of platinum and are applied to computed tomography imaging.Meanwhile,platinum-based nanomaterials have good near-infrared light absorption properties and photothermal conversion efficiency,which make them capable of photothermal imaging and photoacoustic imaging.In addition,by reducing transverse and longitudinal relaxation time,platinum-based nanoplatforms can mediate MRI imaging.In this paper,we report a multimodal imaging system based on platinum-based nanoplatforms for guiding the development of cancer treatment and diagnosis platform and medical application research,and also summarize the prospects of multimodal imaging technology in cancer diagnosis and treatment,report the research progress of platinum-based nanoplatforms in improving the contrast of medical images and enhancing cancer treatment.
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Breast cancer is the most common malignant tumor in women around the world, and it is also a common cause of death in female patients with malignant tumors in China, which seriously harms women's health. At present, with the application of comprehensive treatment approaches, breast cancer has become one of the most effective solid tumors. Platinum drugs are widely used in malignant tumors, and they are also commonly used as effective chemotherapeutic drugs for breast cancer. To regulate the application of platinum drugs in breast cancer, the experts from Breast Cancer Group, Branch of Oncologist, Chinese Medical Doctor Association, discuss and approve the "Guidelines for clinical application of platinum drugs in breast cancer (2023 edition)" . This guideline is developed from the "Expert consensus on the clinical application of platinums in advanced breast cancer (2020 version)" , which is updated from the latest evidence based on breast cancer at home and abroad, for platinum drugs in breast cancer clinical use, application scheme, efficacy analysis and treatment of adverse effects. This guideline aims to guide clinicians to use drugs rationally, and to further standardize the diagnosis and treatment.
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Femelle , Humains , Tumeurs du sein/anatomopathologie , Platine/usage thérapeutique , Consensus , ChineRésumé
Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.
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Humains , Tumeurs du sein triple-négatives/anatomopathologie , Réparation de l'ADN , Mutation , Association thérapeutique , Altération de l'ADNRésumé
Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.
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Humains , Tumeurs du sein triple-négatives/anatomopathologie , Réparation de l'ADN , Mutation , Association thérapeutique , Altération de l'ADNRésumé
Objective:To analyze the related factors of neurotoxicity induced by oxaliplatin chemotherapy in patients with colorectal cancer and its prevention and treatment strategies.Methods:A total of 300 patients with colorectal cancer treated with oxaliplatin in Zhejiang Cancer Hospital from January 2018 to December 2020 were randomly selected for baseline collection using the convenience sampling method. The occurrence of oxaliplatin-induced peripheral neurotoxicity (OIPN) was statistically analyzed. The factors that affect the occurrence of OIPN were analyzed using univariate analysis.Results:There was a significant difference in OIPN score between patients of different genders, between patients who had different education levels, between patients who had different occupations, and between patients who lived in different long-term residence places ( t = 7.29, 3.39, 2.53, 18.11, all P < 0.05). There was no significant difference in OIPN score between patients adhering to different religion's beliefs, between patients married and not, between patients who lived with and without members, between patients who paid medical costs and not, and between patients who had a previous history of smoking and not ( t = 3.25, 0.37, 0.69, 2.39, 0.15, all P > 0.05). There was a significant difference in OIPN score between patients with different tumor-node-metastasis stages, between patients who received medication via different administration routes, and between patients who received different times of oxaliplatin administration ( t = 8.40, 3.34, 3.49, all P < 0.05). Conclusion:Medical staff should pay attention to the occurrence of OIPN in patients with colorectal cancer treated with oxaliplatin, focus on the patient's factors related to the disease, and take correct and effective coping strategies promptly to reduce the adverse reactions, improve the quality of life, and ensure the therapeutic effect.
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Objective To investigate the efficacy of bevacizumab combined with paclitaxel and platinum-based chemotherapy in advanced metastatic cervical cancer and its effect on T lymphocyte subsets and tumor markers. Methods Sixty patients with advanced metastatic cervical cancer (treated in our hospital) were randomly divided into control (30 cases) and treatment (30 cases) groups. All patients were given radiotherapy; the control group received paclitaxel and platinum-based chemotherapy, whereas the treatment group received the same with added bevacizumab. The pain conditions (visual analog score (VAS)) and quality of life (Karl Fischer quality of life (KPS)), clinical efficacy, T lymphocyte subset levels (CD3+, CD4+, and CD8+), tumor markers (carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and squamous epithelial carcinoma-associated antigen (SCCA)) and adverse reactions were compared between the two groups. Results The VAS score, serum CA125, CEA, SCCA, and CD8+ level were significantly reduced in both groups after treatment (P < 0.05), and it significantly decreased in the treatment group compared with the control group (P < 0.05). KPS score, CD3+, and CD4+ levels significantly increased after treatment in the two groups (P < 0.05), and compared with the control group, the treatment group significantly increased (P < 0.05). Moreover, the total effective rate (66.67%) was significantly higher than that in the control group (40.00%) (P < 0.05), and no significant difference existed in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Bevacizumab combined with paclitaxel and platinum-based chemotherapy can effectively reduce the pain and improve the immune function and quality of life of patients with advanced metastatic cervical cancer. This chemotherapy is also safe and effective.
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Objective To investigate the efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer.Methods A total of 107 patients with platinum-sensitive recurrent epithelial ovarian cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2019 to December 2020 were selected as the subjects.According to treatment methods,the patients were divided into control group(n=50)and observation group(n=57).The patients in the control group received a first-line chemotherapy regimen of paclitaxel combined with platinum:on the first day,intravenous infusion with paclitaxel injection 135 mg·m-2 was administered;on day 1-3,intravenous drip with cisplatin 50-60 mg·m-2 was administered;21 days was one chemotherapy cycle.On the basis of the treatment in the control group,the patients in the observation group were given fluzoparide capsules orally,150 mg each time,twice a day,and the treatment continued until disease progression or unacceptable toxic reactions occurred;21 days was one chemotherapy cycle.The patients in both groups received three consecutive chemotherapy cycles.The clinical efficacy,prognosis within 2 years after chemotherapy,Karnofsky Performance Status(KPS)score before and after chemotherapy,and incidence of adverse reactions during chemotherapy of patients between the two groups were compared.Results After 3 cycles of chemo-therapy,the disease control rate and objective remission rate of patients in the observation group were significantly higher than those in the control group(x2=5.420,4.220;P＜0.05).Following up to 24 months,the progression free survival of patients in the observation group was significantly longer than that in the control group(t=6.702,P＜0.05);there was no statistically significant difference in 1-year survival rate of patients between the two groups(x2=0.415,P＞0.05);the 2-year survival rate of patients in the observation group was significantly higher than that in the control group(x2=5.420,P＜0.05).Before chemotherapy,there was no statistically significant difference in KPS scores of patients between the two groups(t=0.537,P＞0.05);the KPS scores of patients in the two groups after three cycles of chemotherapy were significantly higher than those before chemotherapy(t=5.604,9.378;P＜0.05);after three cycles of chemotherapy,the KPS score of patients in the observation group was significantly higher than that in the control group(t=2.608,P＜0.05).The patients in both groups experienced hematological and non-hematological adverse reactions during chemotherapy;the main hematological adverse reactions was bone marrow suppression,most of which were Ⅲ ° and Ⅳ ° adverse reactions;the non-hematological adverse reactions included alo-pecia,gastrointestinal reactions,and liver and kidney dysfunction,most of which were Ⅰ°and Ⅱ°adverse reactions.There were no chemotherapy related deaths of patients in both groups.The incidence rates of anemia,thrombocytopenia,neutropenia,leuko-penia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated alanine amino-transferase(ALT)of patients during chemotherapy in the control group were 68.00％(34/50),72.00％(36/50),58.00％(29/50),68.00％(34/50),22.00％(11/50),26.00％(13/50),24.00％(12/50),46.00％(23/50),30.00％(15/50),50.00％(25/50),20.00％(10/50),10.00％(5/50),respectively;the incidence rates of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy in the observation group were 61.40％(35/57),63.16％(36/57),49.12％(28/57),52.63％(30/57),21.05％(12/57),22.81％(13/57),24.56％(14/57),42.11％(24/57),29.82％(17/57),47.37％(27/57),21.05％(12/57),10.53％(6/57),respectively.There was no statistically significant difference in the incidences of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy between the control group and the observation group(x2=0.047,0.000,0.041,0.694,0.056,0.000,0.208,0.041,0.184,0.160,0.233,0.102;P＞0.05).Conclusion For patients with platinum-sensitive recurrent ovarian cancer,the combination of paclitaxel and platinum chemo-therapy combined with fluzopril can effectively improve the anti-tumor effect,prolong the progression-free survival,improve survival rate and quality of life,and the adverse reactions are controllable.
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Growth differentiation factor 15(GDF15) is a member of transforming growth factor β superfamily. Animal studies find that GDF15, bounding with centrally expressed receptors, reduces body weight by inhibiting food intake and by enhancing energy metabolism. In addition, GDF15 is also involved in the effects of tumor cachexia and platinum-based chemotherapy on body weight. GDF15 and its receptor could be potential targets for the treatment of such diseases.
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Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.
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Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.
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Humains , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Altération de l'ADN , Réparation de l'ADN , Préparations pharmaceutiques , Platine/usage thérapeutique , Composés du platine/usage thérapeutique , Tumeurs du sein triple-négatives/génétiqueRésumé
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
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Although adding platinum to taxane- and anthracycline-based neoadjuvant chemotherapy regimens for triple-negative breast cancer (TNBC) patients can significantly improve the pathological complete response (pCR) rate and long-term survival, it is associated with higher treatment-related adverse events (AEs) . Current researches focus on the response predictors to select patients who may benefit from platinum-based chemotherapy. Homologous recombination deficiency (HRD) can identify patients who truly need platinum drugs, that is, those with BRCA wild-type but HRD tumors. Results suggest that anthracycline-based chemotherapy is sufficient for BRCA mutation carriers and that non-HRD carriers will not benefit from the added carboplatin.
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Objective:To compare the efficacy and prognosis of elective nodal irradiation (ENI) combined with nedaplatin chemotherapy and involved field irradiation (IFI) combined with nedaplatin chemotherapy in the radical radiotherapy treatment of patients with cervical or upper thoracic esophageal cancer.Methods:Seventy-eight patients with cervical or upper thoracic esophageal cancer in Hai'an Traditional Chinese Medicine Hospital from February 2017 to February 2020 were selected and divided into ENI group and IFI group according to random number table method, with 39 cases in each group. The ENI group was treated with ENI combined with nedaplatin chemotherapy, while the IFI group was treated with IFI combined with nedaplatin chemotherapy. After 2 months of treatment, the therapeutic effect and the dose of lung irradiation were compared between the two groups, and the occurrence of adverse reactions and prognosis were compared.Results:The total effective rate and disease control rate were 69.23% (27/39) and 82.05% (32/39) in IFI group, and 64.10% (25/39) and 74.36% (29/39) in ENI group, there was no significant difference between the two groups ( χ2 = 0.23, P = 0.631; χ2 = 0.68, P = 0.411). The lung irradiation doses of V 5 Gy and V 20 Gy in IFI group were lower than those in ENI group (both P < 0.05). The incidence rates of bone marrow suppression and radiation lung injury in IFI group were lower than those in ENI group (all P < 0.05). By the end of follow-up, the survival rates of IFI group and ENI group were 76.92% (30/39) and 66.67% (26/39), respectively. There was no significant difference in overall survival between the two groups ( χ2 = 1.06, P = 0.300). Conclusions:ENI and IFI combined with nedaplatin chemotherapy in the radical radiotherapy treatment of cervical and upper thoracic esophageal cancer have similar efficacy and prognosis, but IFI can reduce the lung radiation dose and the incidence of adverse reactions.
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DNA damage repair (DDR) defects occurred in 8%-16% of metastatic castration resistant prostate cancer (mCRPC). DDR gene mutation was related to poorer prognosis. Patients with DDR gene mutation, especially BRCA1/2 mutation, showed high sensitivity to poly ADP-ribose polymerase inhibitor (PARPi) and platinum.
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The common epidermal growth factor receptor (EGFR) mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-tyrosine kinase inhibitors (EGFR-TKI). However, the clinical outcome and response to treatment for many other rarer mutations are still unclear. In this study, we report the results of Brazilian patients in stage IB-IIIA non-small cell lung cancer (NSCLC) following complete resection with minimal residual disease and EGFR mutations treated with adjuvant chemotherapy and/or EGFR-TKIs. The frequency of EGFR mutations was investigated in 70 cases of early stage NSCLC. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, as well as in exons 3, 7, 14, 16, 22, 27, and 28, and/or the presence of different mutations in a single tumor (complex mutations) are considered rare. EGFR mutations were detected in 23 tumors (32.9%). Fourteen cases carried rare mutations and were treated with platinum-based chemotherapy and two cases were treated with erlotinib. The clinical outcome is described case by case with references to the literature. Notably, we found two rare EGFR mutations and one of them with an unknown response to chemotherapy and/or EGFR-TKIs. We have provided complementary information concerning the clinical outcome and treatment of patients with early stage NSCLC for several rare EGFR mutations not previously or only rarely reported. Description of cases harboring rare mutations can support the decision-making process in this subset of patients.