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前列腺癌诊断与治疗中分子信号通路的新见解及当前进展。

New insights into molecular signaling pathways and current advancements in prostate cancer diagnostics & therapeutics.

作者信息

Thakur Neha, Quazi Sameer, Naik Bindu, Jha Saurabh Kumar, Singh Pallavi

机构信息

Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, Uttarakhand, India.

Department of Chemistry, Akshara First Grade College, Bengaluru, India.

出版信息

Front Oncol. 2023 Aug 17;13:1193736. doi: 10.3389/fonc.2023.1193736. eCollection 2023.

Abstract

Prostate adenocarcinoma accounts for more than 20% of deaths among males due to cancer. It is the fifth-leading cancer diagnosed in males across the globe. The mortality rate is quite high due to prostate cancer. Despite the fact that advancements in diagnostics and therapeutics have been made, there is a lack of effective drugs. Metabolic pathways are altered due to the triggering of androgen receptor (AR) signaling pathways, and elevated levels of dihydrotestosterone are produced due to defects in AR signaling that accelerate the growth of prostate cancer cells. Further, PI3K/AKT/mTOR pathways interact with AR signaling pathway and act as precursors to promote prostate cancer. Prostate cancer therapy has been classified into luminal A, luminal B, and basal subtypes. Therapeutic drugs inhibiting dihydrotestosterone and PI3K have shown to give promising results to combat prostate cancer. Many second-generation Androgen receptor signaling antagonists are given either as single agent or with the combination of other drugs. In order to develop a cure for metastasized prostate cancer cells, Androgen deprivation therapy (ADT) is applied by using surgical or chemical methods. In many cases, Prostatectomy or local radiotherapy are used to control metastasized prostate cancer. However, it has been observed that after 1.5 years to 2 years of Prostatectomy or castration, there is reoccurrence of prostate cancer and high incidence of castration resistant prostate cancer is seen in population undergone ADT. It has been observed that Androgen derivation therapy combined with drugs like abiraterone acetate or docetaxel improve overall survival rate in metastatic hormone sensitive prostate cancer (mHSPC) patients. Scientific investigations have revealed that drugs inhibiting poly ADP Ribose polymerase (PARP) are showing promising results in clinical trials in the prostate cancer population with mCRPC and DNA repair abnormalities. Recently, RISUG adv (reversible inhibition of sperm under guidance) has shown significant results against prostate cancer cell lines and MTT assay has validated substantial effects of this drug against PC3 cell lines. Current review paper highlights the advancements in prostate cancer therapeutics and new drug molecules against prostate cancer. It will provide detailed insights on the signaling pathways which need to be targeted to combat metastasized prostate cancer and castration resistant prostate cancer.

摘要

前列腺腺癌占男性癌症死亡人数的20%以上。它是全球男性中第五大最常被诊断出的癌症。前列腺癌的死亡率相当高。尽管在诊断和治疗方面取得了进展,但仍缺乏有效的药物。由于雄激素受体(AR)信号通路的触发,代谢途径发生改变,并且由于AR信号缺陷导致二氢睾酮水平升高,加速了前列腺癌细胞的生长。此外,PI3K/AKT/mTOR通路与AR信号通路相互作用,并作为促进前列腺癌的前体。前列腺癌治疗已分为腔面A型、腔面B型和基底亚型。抑制二氢睾酮和PI3K的治疗药物已显示出对抗前列腺癌的有希望的结果。许多第二代雄激素受体信号拮抗剂可单独使用或与其他药物联合使用。为了开发治疗转移性前列腺癌细胞的方法,通过手术或化学方法应用雄激素剥夺疗法(ADT)。在许多情况下,前列腺切除术或局部放疗用于控制转移性前列腺癌。然而,据观察,在前列腺切除术或去势术后1.5年至2年,前列腺癌会复发,并且在接受ADT的人群中去势抵抗性前列腺癌的发生率很高。据观察,雄激素剥夺疗法与醋酸阿比特龙或多西他赛等药物联合使用可提高转移性激素敏感性前列腺癌(mHSPC)患者的总生存率。科学研究表明,抑制聚ADP核糖聚合酶(PARP)的药物在患有mCRPC和DNA修复异常的前列腺癌人群的临床试验中显示出有希望的结果。最近,RISUG adv(引导下的精子可逆抑制)已显示出对前列腺癌细胞系有显著效果,MTT试验已证实该药物对PC3细胞系有实质性作用。当前的综述文章强调了前列腺癌治疗的进展以及针对前列腺癌的新药分子。它将提供关于对抗转移性前列腺癌和去势抵抗性前列腺癌需要靶向的信号通路的详细见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f402/10469924/711c9f49c608/fonc-13-1193736-g001.jpg

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