相关实验视频

Updated: Jun 28, 2025

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

Published on: December 16, 2022

LP-184是一种新型的酸性分子,对具有同源重组缺陷的多种固体瘤表现出抗癌活性

Aditya Kulkarni¹, Jianli Zhou¹, Neha Biyani¹

¹Lantern Pharma Inc., Dallas, Texas.

Cancer research communications

|April 17, 2024

概括

新型DNA破坏剂LP-184在治疗同源重组缺陷 (HRD) 的各种癌症方面显示出显著的前景. 这种药物在临床前模型中表现出强大的抗瘤活性和与现有疗法的协同作用,支持其临床评估.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

与同源重组 (HR) 相关的基因变异在几个固体瘤中很常见,包括前列腺,乳腺,卵巢,肺和结肠癌.
这些变化表明对DNA损伤剂的潜在敏感性.
小分子乙基富伦原药LP-184由前列腺素还原酶1 (PTGR1) 激活,前列腺素还原酶1 (PTGR1) 是一种在固体瘤中经常升高的酶.

研究的目的:

为了研究LP-184在向HR功能受损的瘤中的有效性.
阐明LP-184作为DNA破坏剂的作用机制.
评估LP-184作为泛HRD癌症治疗的潜力.

主要方法:

评估LP-184诱导HR缺乏 (HRD) 癌细胞中的DNA双链断裂的能力.
在关键HR组件BRCA2和ATM耗尽时对LP-184的敏感性确定.
评估了LP-184在各种HRD癌症模型中的功效,包括器官和患者衍生异体移植 (PDX).
研究了LP-184和PARP抑制剂 (PARPi) 之间的协同作用.

主要成果:

在HRD癌细胞中,LP-184诱导了DNA双链断裂的升高.
由于BRCA2或ATM的枯竭,对LP-184的敏感性增加了多达12倍.
在各种HRD癌症模型中,LP-184表现出纳米分子功效.
在HRD三阴性乳腺癌 (TNBC) PDX模型中观察到完全和持久的瘤回归,包括对PARPi.Pi耐药的模型.
在卵巢和前列腺癌细胞系和TNBC PDX模型中,LP-184与PARPi显示出强烈的协同作用.

结论:

LP-184显示出作为治疗各种HRD固体瘤的治疗剂的显著潜力.
临床前发现支持在患有HRD癌症的患者中继续对LP-184进行临床评估.
LP-184代表了一种有前途的新药,用于治疗缺乏DDR的固体瘤,这些瘤对当前疗法不耐药.

更多相关视频

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Published on: February 24, 2023

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Homologous Recombination

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...