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PI3K/AKT/mTOR Pathway Inhibitor Development

In prostate cancer, oncogenic activation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathways leads to tumor formation, disease progression, and therapeutic resistance. At Alfa Cytology, we are dedicated to offering comprehensive, end-to-end services for PI3K/AKT/mTOR Signaling Pathway Inhibitor Development in Prostate Cancer.

Introduction to PI3K/AKT/mTOR Pathway

Oncogenic activation of PI3K, PKB/AKT, and mTOR pathways in prostate cancer causes tumor formation, disease progression, and therapeutic resistance. There are many genetic causes of deregulation of the PI3K-AKT-mTOR pathway, the most common of which is the loss of function of PTEN. There is a high frequency of genetic alterations associated with the PI3K-AKT-mTOR pathway in primary and metastatic prostate cancer, which indicates that a broad range of events may coexist.

Table 1. Frequency of common genetic alterations in PI3K-AKT-mTOR pathway genes in prostate cancer. (Shorning, B. Y., et al. 2020)

Common Types of Genetic Alterations in PI3K-AKT-mTOR Pathway Genes Frequency in Prostate Cancer
PTEN deletion/mutation 16.4-32.0%
DEPTOR amplification 5.1-21.4%
SGK mutation/amplification 5.6-20.5%(SGK3)
0.2-2.7% (SGK1)
FOXO deletion 0.0-15.2%(FOXO1)
4.5-13.4%(FOXO3)
MAP3K7 deletion 5.9-14.8%
RRAGD deletion 6.5-14.4%
SESNl mutation/deletion 5.4-13.6%
PIK3CA mutation/amplification 5.5-11.5%
PIK3C2B mutation/amplification 1.4-11.5%
PDPKl amplification 0-8.1%

Preclinical Studies for PI3K/AKT/mTOR Pathway Inhibitor in Prostate Cancer

Multiple small molecule inhibitors of the PI3K/Akt/ mTOR pathway have been investigated in both in vitro and in vivo models of prostate cancer.

Inhibitors Experimental Model Results
PI3K Inhibitors
LY294002 p110 transgenic Decreased pAkt by 47%; significant decreases in eIF4G, Mst1 and RanBP2.
Curcumin LNCaP s.c. Decreased tumor growth and cell proliferation, increased apoptosis.
Akt Inhibitors
Celecoxib PC-3 s.c. Inhibited formation of tumors used in combination.
Genistein Orthotopic PC-3 Reduced lung metastasis between 40-60%.
mTOR Inhibitors
Rapamycin PC-3 s.c. 53% tumor volume reduction alone; 80% reduction in combination.
RAD-001 C4-2 intra-tibial Significant decreases in tumor growth with addition of drugs in combination.
CCI-779 PC-3 & DU 145 s.c. Inhibited growth – significant decrease in Ki-67 index.

Our Services

Alfa Cytology has been working on PI3K/AKT/mTOR pathway research for prostate cancer and focuses on providing one-stop development services according to the specific needs of our clients. We provide our clients with excellent development services based on our specialized technical knowledge and deep experience.

PI3K/AKT/mTOR Pathway Inhibitor Development Types

Monoclonal Antibody

Offering all-in-one services for creating monoclonal antibodies, involving selecting B-cells, using hybridoma tech, purifying antibodies, and making further engineering tweaks.

Bispecific Antibody

Creating bispecific cloned antibodies involves recombinant DNA or cell fusion techniques and making sure the light and heavy chains pair correctly to work as a bispecific antibody.

ADC Development

Developing ADCs means linking a toxic drug to a monoclonal antibody with a chemical linker for precise delivery, targeting tumor cells strongly while minimizing harm to healthy ones.

One-stop Solutions for PI3K/AKT/mTOR Pathway Inhibitor Development

Alfa Cytology offers small molecule inhibitors development targeted to PI3K/AKT/mTOR signaling pathway in prostate cancer, including but not limited to the following.

iconDrug Discovery

The process of drug discovery typically involves several stages, including target identification and validation, hit identification and lead optimization, and preclinical testing.

iconEfficacy Evaluation

In vitro efficacy evaluation offers rapid, high-throughput initial screening, while in vivo efficacy evaluation provides necessary data to validate drug efficacy and safety in a physiological setting.

iconDMPK/ADME

Assessing the in vitro ADME and in vivo PK of cancer drugs ensures their efficacy and safety in living organisms, offering vital data for optimizing dosage and dosing schedules.

iconSafety Assessment

Local toxicity and safety of cancer drugs are assessed using general toxicology, genetic toxicology, reproductive toxicology, and immunotoxicity of cancer drugs.

Our Advantages

Our company is committed to providing customized one-stop services to accelerate your project development. With professional knowledge, we are committed to providing you with reliable experimental solutions, efficiently providing you with round-the-clock development services to ensure that your development is of low cost and confidentiality.

Qualified Experiment

Timely Delivery

Cost-Effective Services

Highly Confidential

At Alfa Cytology, our mission is to advance prostate cancer therapy development by providing clients with efficient, innovative, and reliable solutions. If you are interested in our services, please don't hesitate to contact us for further information and pricing details.

Reference

  1. Shorning, B. Y., et al. The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. International journal of molecular sciences. 2020, 21(13): 4507.
notification For research use only.

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