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The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers
Fernanda Andrade1,2,3, Júlia German-Cortés1,2, Sara Montero1,2
1Clinical Biochemistry, Drug Delivery and Therapy Group (CB-DDT), Vall d'Hebron Institut of Research (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
Abstract:
Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers.
Insights
Targeting Kirsten rat sarcoma (KRAS) mutations in cancer is challenging. Nanomedicine offers a promising approach to develop targeted therapies for KRAS-mutated cancers, improving treatment effectiveness.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Kirsten rat sarcoma (KRAS) is a GTPase crucial for cell signaling; its mutations drive 25% of human cancers, notably pancreatic, colorectal, and lung cancers.
- KRAS mutations are linked to aggressive disease, poor prognosis, and resistance to conventional therapies, highlighting the need for novel treatment strategies.
- Current therapeutic strategies targeting KRAS or its pathway have shown limited success due to specificity and effectiveness issues.
Purpose of the Study:
- To review recent advancements in nanotechnology-based therapeutic strategies for KRAS-mutated cancers.
- To explore the potential of nanoparticles in overcoming the limitations of current anti-KRAS therapies.
- To summarize the development of nanomedicines for targeted delivery in KRAS-driven malignancies.
Main Methods:
- Literature review of recent studies on nanomedicine applications in oncology.
- Analysis of nanoparticle-based drug/gene/biomolecule delivery systems for KRAS-targeted therapy.
- Synthesis of information on nanoparticle design and targeting strategies for KRAS-mutated cancer cells.
Main Results:
- Nanoparticles demonstrate potential for enhancing the therapeutic index of anti-cancer agents.
- Nanotechnology enables targeted delivery of therapeutic payloads to KRAS-mutated cancer cells, improving specificity.
- Various nanoparticle platforms are being developed to address the challenges in treating KRAS-driven cancers.
Conclusions:
- Nanomedicine presents a promising avenue for developing effective and specific therapies against KRAS-mutated cancers.
- Targeted delivery systems using nanoparticles can overcome key obstacles in current anti-KRAS treatment approaches.
- Further research in nanomedicine holds significant potential for improving outcomes in patients with KRAS-driven malignancies.
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