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2.
Chin J Cancer Res ; 34(4): 415-421, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36199534

ABSTRACT

Several phosphoinositide 3-kinase (PI3K) inhibitors are currently approved to treat hematolymphatic malignant diseases worldwide, and many drugs that have the same target are in the clinical research stage. In March 2022, duvelisib became the first PI3K inhibitor approved in China indicated for the treatment of hematolymphatic malignant diseases. Meanwhile, linperlisib and copanlisib have almost completed the technical review of the clinical specialty. The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) found that class I PI3K inhibitors can cause various degrees of immune-related adverse events, which are associated with action mechanisms, affecting the benefit-risk assessment of the drugs. On April 21, 2021, the United States Food and Drug Administration (FDA) convened the Oncologic Drugs Advisory Committee (ODAC) meeting to discuss the safety of PI3K inhibitors indicated for hematolymphatic malignancies and their related risk of death. The hematological tumor group of CDE of the China NMPA summarized and combined the data on PI3K inhibitors listed or under technical review for marketing authorization applications and found that such products may have unique efficacy and safety characteristics in Chinese patients with malignant lymphoma.

3.
Medicine (Baltimore) ; 99(41): e22567, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33031304

ABSTRACT

BACKGROUND: We put the meta-analysis into practice to reveal the relationship between the incidence risk of immune-related pneumonitis and the use of programmed cell death-1 (PD-1) and ligand 1 (PD-L1) inhibitors related pneumonitis in cancer patients. METHOD: The meta-analysis was put into practice according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Odds ratio (OR) was evaluated by random effect model. RESULTS: After screening and eligibility assessment, 33 clinical trials involving 19,854 patients were selected and used for the final meta-analysis after selection criteria checked. Compared with chemotherapy, the use of PD-1/PD-L1 inhibitors alone increased the incidence risk of all-grade (OR = 4.29, 95% confidence interval: [2.97, 6.19], P < .00001) and grade 3 to 5 immune-related pneumonitis (OR = 3.53, 95% confidence interval: [2.04, 6.11], P < .00001). Similar trend could also be found when PD-1/PD-L1 inhibitors were prescribed alone or in combination with other anti-tumor therapies. CONCLUSION: Whether PD-1/PD-L1 inhibitors were used alone or combined with other antitumor drugs, the incidence risk of immune-related pneumonitis would be increased.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Neoplasms/drug therapy , Pneumonia/chemically induced , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Humans , Pneumonia/immunology
4.
Epigenomics ; 12(9): 801-809, 2020 05.
Article in English | MEDLINE | ID: mdl-32515221

ABSTRACT

Aim: As one of the early adaptive mechanisms by which cells respond to environmental changes, RNA modification appears to be a very promising target for cancer treatment. Results: RNA modifications are currently a hot topic in epigenetic research. Emerging experimental studies show that expression alterations of multiple m6A enzymes, including demethylase FTO, methyltransferase METTL3 and WTAP, mediate the development of resistance of cancer cells to various treatments. A set of small molecular chemical drugs targeted to these m6A enzymes are under development. Intervention of RNA m6A methylation is a possible therapeutic strategy to overcome drug resistance. Conclusions: RNA m6A methylation may play a crucial role in drug resistance development and intervention in cancer cells.


Subject(s)
Adenosine/analogs & derivatives , Drug Resistance, Neoplasm , Neoplasms/enzymology , Adenosine/metabolism , AlkB Homolog 5, RNA Demethylase , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Cell Cycle Proteins/metabolism , Drug Resistance, Neoplasm/genetics , Humans , Methylation , Methyltransferases/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/radiotherapy , RNA/chemistry , RNA/metabolism , RNA Splicing Factors/metabolism , Radiation Tolerance
5.
Front Oncol ; 9: 866, 2019.
Article in English | MEDLINE | ID: mdl-31552184

ABSTRACT

Purpose: We conducted this study to determine the relationship between PD-1/PD-L1 inhibitors and the incidence risk of peripheral neuropathy in patients with solid tumors. Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Incidence of all-grade and grade 3-5 treatment-related peripheral neuropathy in patients with solid tumors were taken into account. Results: After screening and eligibility assessment, a total of 17 clinical trials involving 10,500 patients were selected for the final meta-analysis. The incidence risk of peripheral neuropathy for all grade was significantly lower in the PD-1/PD-L1 inhibitor group than that of the control group, either monotherapy (OR = 0.08, 95%CI:[0.03, 0.19]) or chemotherapy (OR = 0.05, 95%CI:[0.03, 0.11]). Similar incidence trend could also be seen for the incidence risk of grade 3-5 peripheral neuropathy. When PD-1/PD-L1 inhibitors were used in combination with chemotherapy, the incidence risk of peripheral neuropathy was higher than in the control chemotherapy group, whether it was all-grade (OR = 1.22, 95%CI:[1.00, 1.49]) or grade 3-5 degree (OR = 1.74, 95%CI:[1.03, 2.92]). Conclusion: Compared with chemotherapy, incidence risk of peripheral neuropathy related to PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while PD-1/PD-L1 inhibitor increased the incidence risk of peripheral neuropathy when it was combined with chemotherapy.

6.
Zhongguo Fei Ai Za Zhi ; 20(3): 205-212, 2017 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-28302224

ABSTRACT

The high morbidity and mortality of non-small cell lung cancer (NSCLC) did influence the quality of life of tumor patients world-wide. There is an urgent need to develop new therapies that have high anti-tumor activity and low toxicity side effects. It is widely accepted that autophagy can play diverse roles in carcinogenesis, such as induces pro-death of lung cancer cells or helps the escape from cell death, making it become a proper anticancer target. It's believed that various monomers of Chinese traditional medicine closely correlates to anti-NSCLC activities, and that even could affect the acquired multiple drug resistance (MDR). Furthermore, autophagy might be the underling mechanisms which could play a role as the candidate targets of natural active compounds. Recent studies of terpenoids, alkaloid, dietary polyphenols, saponins and other active ingredients that extracted from a large variety of herbs suggest that different monomer compounds could either regulate the activity of pro-death autophagy or influence the level of protective autophagy of NSCLC cells, thus changing their drug sensitivity and cell viability. This paper aims to give a systemic description of the latest advances about natural compounds and their derivatives that involved in tumorigenesis of NSCLC via inducing the autophagy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Autophagy/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Medicine, Chinese Traditional/methods , Antineoplastic Agents, Phytogenic/chemistry , Carcinogenesis/drug effects , Humans
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