Therapeutic strategies of dual-target small molecules to overcome drug resistance in cancer therapy

Ye, Jing; Wu, Junhao; Liu, Bo

doi:10.1016/j.bbcan.2023.188866

Cited by 20 publications

(18 citation statements)

References 260 publications

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“…In this case, a multifunctional TPE derivative TPE-Lenalidomide was designed and prepared through nucleophilic addition (Scheme S1), and the details are described in the Experimental Section. The chemical structure and molecular weight of TPE-CHO and TPE-Lenalidomide were fully characterized by 1 H and 13 C nuclear magnetic resonance spectroscopy and mass spectrometry (Figures S1−S6).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Found: 602.24408. 1 H NMR, 13 C NMR and mass spectra of TPE-CHO were shown in Figures S4−S6, respectively.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Cancer remains as one of the most significant diseases that seriously threatens human health all over the world. − In order to effectively inhibit malignant tumor and prolong survival, varieties of drug delivery systems and polymer prodrugs have been developed. − However, most of them are restricted by their low drug loading capacity, and serious cumulative cytotoxicity. , By comparison, small-molecule prodrugs − have the advantage of high loading capacity and easy metabolism for cancer therapeutics. Typically, Yan et al developed an amphiphilic small-molecule prodrug by integrating a hydrophilic anticancer drug and a hydrophobic anticancer drug via a hydrolyzable ester linkage and proposed the concept of amphiphilic drug–drug conjugate (ADDC), which opens up a new way for self-delivery systems.…”

Section: Introductionmentioning

confidence: 99%

“…We hope that this facile and versatile strategy is of high applied value to design and prepare probe-drug structural small-molecule prodrugs via a Schiff base linkage for cancer-targeted theranostics.The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsanm.3c03611. Materials and instrumentation, 1 H NMR,13 C NMR, and mass spectra of TPE-CHO and TPE-Lenalidomide; aqueous solubility of TPE-CHO and Lenalidomide with different pH values; PL spectra of TPE-Lenalidomide (10 −4 M) in DMSO/H 2 O with different fractions of water (fw); relative fluorescence intensity per pixel of L929 or 4T1 cells after incubation with 1 mL of TPE-CHO and TPE-Lenalidomide (66.5 × 10 −12 mol/L) for 1.5, 6, and 24 h at 37 °C (PDF) Science and Technology Program of Guangzhou (No. 2019050001 and 202102020757), Guangdong Basic and Applied Basic Research Foundation (No.…”

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confidence: 99%

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Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

Mai,

Cao,

Cheng

et al. 2023

ACS Appl. Nano Mater.

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To develop multifunctional small-molecule prodrugs is highly desirable for cancer treatment but remains challenging in intrinsic traceability. As an acid-cleavable linkage, a Schiff bases benefiting from its distinctive fluorescence quenching ability was selected to prepare a small-molecule prodrug with cancer-targeted and self-indicating. In this study, we designed and developed a multifunctional self-assembled nanobomb of amphiphilic TPE-Lenalidomide prodrug, which comprises a hydrophobic aggregation-induced emission (AIE) probe 4-(1,2,2triphenylvinyl)benzaldehyde (TPE-CHO) and a hydrophilic anticancer drug Lenalidomide via a Schiff base linkage. We investigated the synergistic effect of d-PET and C�N isomerization which would keep the fluorescence of TPE-Lenalidomide in the "always off" state by density functional theory (DFT) calculation. Once reaching the pathological site, such a vesicular nanobomb of TPE-Lenalidomide will be acidolyzed to release the AIE probe and Lenalidomide molecules simultaneously, consequently realizing high-efficiency effects of tumor imaging and cancer therapy (cell viability: normal cell L929, ∼79.49%; cancer cell 4T1, ∼27.08%; p = 0.000118). This work may pave an avenue to prepare small-molecule prodrugs for tumor-targeted diagnosis and cancer therapy.

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Section: ■ Results and Discussionmentioning

confidence: 99%

“…Found: 602.24408. 1 H NMR, 13 C NMR and mass spectra of TPE-CHO were shown in Figures S4−S6, respectively.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

Mai,

Cao,

Cheng

et al. 2023

ACS Appl. Nano Mater.

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“…One agent simultaneously regulating two druggable targets typically exhibits fewer side events and lower toxicity when compared to drug combination techniques. In order to combat medication resistance in cancer therapy, the dual‐target small molecule has been intensively researched (Ye et al., 2023).…”

Section: Introductionmentioning

confidence: 99%

In vivo anticancer study of sodium 2‐[(4‐oxidobenzylidene)amino]‐6H‐1,3,4‐thiadiazine‐5‐olate against Ehrlich ascites carcinoma via targeting PI3K/mTOR pathway

Rizzk,

El‐Deen,

Behery

et al. 2024

Chem Biol Drug Des

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Abstract1,3,4‐Thiadiazine‐based components have gained the attention as they afford significant intervention for cancer therapy. We aimed at assessing the in vivo antitumor activity of sodium 2‐[(4‐oxidobenzylidene) amino]‐6H‐1,3,4‐thiadiazine‐5‐c (SOTA) versus Ehrlich ascites carcinoma (EAC) cells in female mice's peritoneal cavity. An advantageous interaction of the test compound with the receptors p53 (2J1X), Caspase‐3 (3KJF), mTOR (3QAR), and PI3K (4JPS) was revealed by the docking study. The in vivo study of the test compound against EAC, equated with the EAC control mice, EAC bearing mice that received the test compound by i.p. injection proven a substantial decrease in the viability of tumor cell by 70%. Treatment with the tested compound increased total antioxidants capacity and decreasing malondialdehyde levels. Also, the apoptotic activity of the test compound was confirmed by up regulation of caspase‐3 and p53 and downregulation of PI3K and mTOR. Through the liver, kidney, and heart function assessments, the examined component has no adverse effects on either of the two organs, which were supported by a histological study. Significant positive and negative associations among variables were discovered, according to our research. Through the induction of apoptosis and antioxidant effects, the test compound show potential anticancer activity against EAC cells. The treatment with SOTA eliminated most of the pathological abnormalities brought on by EAC cells in mice, according to the results of tests on the liver, kidney, and heart as well as the histological investigation. Taking together, the tested compound SOTA is promising chemotherapeutic agent as supported by targeting PI3k/mTOR pathway.

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Impact of molecular diagnostics and targeted cancer therapy on patient outcomes (MODIFY): a retrospective study of the implementation of precision oncology

Dang,

Schritz,

Goncharenko

et al. 2024

Molecular Oncology

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High‐throughput genomic analyses are being implemented in clinical practice. MODIFY is a retrospective study of the first introduction of genomic profiling and molecular tumor boards in the country of Luxembourg. The primary objective was to assess whether patients derived a clinical benefit by measuring the percentage of patients who presented a progression‐free survival (PFS) on matched therapy (PFS2) 1.3‐fold longer than PFS on previous therapy (PFS1). A total of 94 patients were included. In total, 45 patients (53.57% of patients with successful next‐generation sequencing [NGS] analysis) were found to have an actionable mutation. Of these, 11 patients received the treatment recommended by the molecular tumor board, another 12 received best‐supportive care, and 20 were treated with conventional therapy. PFS2 and PFS1 data were available for eight patients. The PFS2/PFS1 ratio was ≥ −1.3 in 62.5% (n = 5/8; CI [30.38, 86.51]) of patients; three patients showed a partial response, and median overall survival (OS) was 7.3 months. Although the examined population was small, this study further supports evidence indicating that patients with advanced cancer benefit from molecular profiling and targeted therapy.

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Therapeutic strategies of dual-target small molecules to overcome drug resistance in cancer therapy

Cited by 20 publications

References 260 publications

Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

In vivo anticancer study of sodium 2‐[(4‐oxidobenzylidene)amino]‐6H‐1,3,4‐thiadiazine‐5‐olate against Ehrlich ascites carcinoma via targeting PI3K/mTOR pathway

Impact of molecular diagnostics and targeted cancer therapy on patient outcomes (MODIFY): a retrospective study of the implementation of precision oncology

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