PFKFB3作为割耐药前列腺癌的多方面的驱动因素和治疗标
Lin Chen1,2, Yu-Xin Xu1,2, Ying-Ying Ren1,2
1School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Cell death & disease
|October 24, 2025
概括
通过改变新陈代谢,PFKFB3的上调驱动了抵抗割的前列腺癌 (CRPC) 的进展. 抑制PFKFB3对CRPC治疗有希望,可能提高化疗的有效性.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 代谢途径 代谢途径
背景情况:
- 抗割前列腺癌 (CRPC) 代表前列腺癌 (PCa) 的晚期阶段,治疗选择有限.
- 耐药性是控制CRPC的一个重大挑战,需要新的治疗策略.
- 了解驱动CRPC进展的分子机制对于开发有效治疗方法至关重要.
研究的目的:
- 调查6-果糖-2-激酶/果糖-2,6-双酸酶3 (PFKFB3) 在前列腺癌 (PCa) 和割抵抗性前列腺癌 (CRPC) 中的作用.
- 通过检查其抑制的影响,探索PFKFB3作为CRPC潜在的治疗点.
- 阐明在CRPC进展中由PFKFB3调节的潜在分子通路.
主要方法:
- 在PCa组织和CRPC细胞系中分析PFKFB3表达.
- 在CRPC细胞中,基因淘汰和小分子抑制PFKFB3.
- 细胞生长,入侵和增殖的评估.
- 调查PFKFB3对PI3K/Akt-Wnt/β-catenin信号通路的影响.
- 评估与PFKFB3抑制剂和多塞塔克塞尔的联合治疗.
主要成果:
- 在PCa组织和CRPC细胞系中,PFKFB3被显著上调.
- 抑制或抑制PFKFB3抑制了CRPC细胞的生长和入侵.
- 过度表达PFKFB3促进了CRPC细胞中的恶性行为.
- PFKFB3调节PI3K/Akt-Wnt/β-catenin通路,增强瘤细胞的增殖.
- 与PFKFB3抑制剂和多塞克塞尔的联合治疗显示出协同作用的抗CRPC作用和降低毒性.
结论:
- PFKFB3介导的代谢重编程是CRPC进展的关键驱动因素.
- PFKFB3代表了CRPC的一个有前途的治疗标.
- 对PFKFB3抑制剂的进一步研究是有必要的,以开发精确的针对性治疗CRPC.
相关概念视频
Targeted Cancer Therapies
8.6K
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...
There are several types of targeted therapies against...
8.6K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
436
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
436
Mitogens and the Cell Cycle
7.7K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.7K
Combination Therapies and Personalized Medicine
5.9K
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...
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...
5.9K
Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
PI3K/mTOR/AKT Signaling Pathway
5.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.3K


