针对性抗癌疗法开发KRAS抑制剂的当前策略和未来维度
Laura D'Alessio-Sands1, Joshua Gaynier1, Victoria Michel-Milian1
1South University School of Pharmacy, Savannah, Giorgia, USA.
Drug development research
|January 12, 2025
概括
克拉斯突变驱动许多转移性癌症,但新的向疗法正在出现. 本综述探讨了直接抑制和有针对性的降解等新策略,以克服KRAS驱动的癌症.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- KRAS原基因突变在转移性癌症中普遍存在,包括胰腺,肺和结直肠类型.
- KRAS突变与传统癌症治疗的反应不佳有关,突出显示了针对性治疗的必要性.
- 从历史上看,KRAS被认为是"不可抗药",但在已批准的药物和正在进行的开发方面取得了重大进展.
研究的目的:
- 审查KRAS向分子的发展.
- 强调KRAS抑制的多种药物设计策略.
- 评估KRAS抑制剂的药理属性和临床潜力.
主要方法:
- 通过小分子结合剂直接抑制KRAS突变.
- 使用小分子结合剂和环林A复合物抑制激活的KRAS突变体.
- 针对KRAS突变的有针对性的降解,使用蛋白质溶解向金马 (PROTACs).
主要成果:
- 针对KRAS向治疗,正在研究多种药物设计策略.
- 几种KRAS抑制剂正在临床开发中,其中一些已经获得批准.
- 该审查评估了各种KRAS向方法的疗效和临床益处.
结论:
- 克拉斯现在是一个可用药的目标,超越了其"不可用药"的地位.
- 不同的策略正在推动KRAS抑制剂用于癌症治疗的开发.
- 未来的研究将专注于优化KRAS抑制剂以提高抗癌疗效.
更多相关视频
12:40A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
14.8K
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
13.6K
相关概念视频
Targeted Cancer Therapies
7.4K
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...
7.4K
Combination Therapies and Personalized Medicine
4.8K
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...
4.8K
Treatment Resistant Cancers
3.2K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
Inhibition of Cdk Activity
4.6K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Mitogens and the Cell Cycle
6.4K
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...
6.4K
Cancer Therapies
7.5K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.5K
