Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Methods of treating squamous cell carcinomas with farnesyltransferase inhibitors

A technology of squamous cell carcinoma, transferase, applied in the field of cancer treatment

Pending Publication Date: 2021-12-14
KURA ONCOLOGY
View PDF77 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, patients respond differently to FTI therapy
Therefore, there is an unmet need for methods of predicting the responsiveness of subjects with cancer to FTI therapy or of selecting cancer patients for FTI therapy

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Methods of treating squamous cell carcinomas with farnesyltransferase inhibitors
  • Methods of treating squamous cell carcinomas with farnesyltransferase inhibitors
  • Methods of treating squamous cell carcinomas with farnesyltransferase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0383] Enhanced in vivo efficacy of tipirfarnib in HNSCC with high H-Ras expression or high H / N+K ratio

[0384] Tumors were generated by inoculating primary human tumor model fragments (2-3 mm in diameter) subcutaneously in the right flank of female BALB / c nude mice or Nu / nu mice (6-8 weeks). When the average tumor size reaches about 250-350mm 3 , the mice were randomly divided into treatment groups. Animals were dosed with tipifarnib vehicle (20% w / v hydroxypropyl-β-cyclodextrin) or tipifarnib at a dose of 80 mg / kg BID PO for 3-4 weeks and tumors were measured weekly Size twice.

[0385] Selected patient-derived xenograft (PDX) models of HNSCC were used to determine the ability of tipirfarnib to inhibit tumor growth. Selected models express different expression levels of H-Ras, or have different ratios of higher H-Ras expression / combined expression of K-Ras and N-Ras ("H / K+N ratio"). The expression levels of H-Ras, K-Ras and N-Ras in these PDX models were determined by R...

Embodiment II

[0394] Enhanced in vivo efficacy of tipifarnib in esophageal squamous cell carcinoma but not breast cancer with high H / N+K ratio

[0395] As described in Example 1, a PDX model of esophageal squamous cell carcinoma (ESCC) (ES0204 or ES0172) or breast cancer (BR1282 or BR1458) was inoculated subcutaneously in the flank of nude mice. The H / K+N ratios for these models are detailed in Table 1. like Figure 2A and Figure 2B As shown in , tipirfarnib effectively inhibits with a relatively high H / K+N ratio ( Figure 2A Tumor growth in both ES0172 (p=0.02) and ES0204 (p=0.04) models of ). However, although BR1282 (p=0.53) or BR1458 (p=0.28) breast cancer PDX models also had relatively high H / K+N ratios ( Figure 2C and Figure 2D ), but this effect was not observed in these models. Therefore, high H-Ras expression or high H / K+N ratio is specifically associated with the efficacy of FTIs (such as tipifarnib) in SCC such as HNSCC, ESCC and urothelial carcinoma, but not other non-s...

Embodiment III

[0397] Synergistic effect of tipifarnib and second therapy in HNSCC with high H-Ras expression or high H / N+K ratio

[0398] PDX HNSCC models (HN3411 and HN2594) were inoculated subcutaneously in the flank of mice as described in Example 1. Following tumor development, the mice are administered vehicle, tipifarnib, the second active agent, or a combination of tipifarnib and the second active agent. The second agent is the alkylating agent cisplatin, the EGFR inhibitor cetuximab, or the CDK inhibitor palbociclib. As indicated, cisplatin ( Figure 3B ) and palbociclib ( Figure 3C ) do not have any activity when used alone. However, both cisplatin and palbociclib caused further inhibition of tumor growth when combined with tipifarnib compared to tipifarnib alone ( Figure 3B and Figure 3C ). Thus, tipifarnib not only directly inhibits tumor growth in HNSCC, but also sensitizes tumors to other treatments such as cisplatin or palbociclib.

[0399] Both cetuximab and tipifar...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to the field of cancer therapy. Specifically, provided are methods of treating Squamous Cell Carcinoma in a subject with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on the expression level of H-Ras.

Description

[0001] cross reference [0002] This application claims priority benefit of U.S. Provisional Application No. 62 / 992,749, filed March 20, 2020, and also claims priority benefit of U.S. Provisional Application No. 62 / 826,771, filed March 29, 2019. Each of the aforementioned related applications is incorporated herein by reference in its entirety. technical field [0003] The present invention relates to the field of cancer therapy. In particular, provided herein are methods of treating squamous cell carcinoma with inhibitors of farnesyltransferase. Background technique [0004] Stratification of patient populations to improve treatment response rates is increasingly valuable in the clinical management of cancer patients. Farnesyl transferase inhibitors (FTIs) are therapeutic agents that have utility in the treatment of cancers such as squamous cell carcinoma ("SCC"). However, patients respond differently to FTI therapy. Accordingly, there is an unmet need for methods of pr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/4709A61K45/06A61P35/00
CPCA61K31/4709A61P35/00A61K45/06A61K39/464411A61K39/46434A61K2239/31A61K39/4611A61K39/00A61K2239/38A61K2300/00A61K33/243A61K31/4545A61K31/551A61K31/045A61K31/223A61K31/365A61K31/4155A61K31/4439A61K31/496A61K31/519A61K31/55A61K31/5513A61K39/3955
Inventor 弗朗西斯·巴罗斯刘异
Owner KURA ONCOLOGY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com