Project information
Exploring Pentamethinium Salts for Antimetastatic Efficacy in Melanoma Model: Intratumoral vs. Systemic Delivery Strategies in Neoadjuvant Approach (Antimetastatic potential of PMS in melanoma model)

Project Identification
Project Period
1/2024 - 12/2024
Investor / Pogramme / Project type
Masaryk University
MU Faculty or unit
Faculty of Medicine

In recent decades, significant progress has been made in the field of cancer research, particularly in the diagnosis and treatment of various types of cancer. Despite these advancements, the challenge of dealing with metastases remains substantial. In this project, we will focus on a melanoma model, where distant organ metastasis is the leading cause of death. Melanoma is often considered as one of the most challenging cancers to treat with conventional approaches, including chemotherapy, radiation therapy, and early-stage targeted therapies. Melanoma differs from non-melanoma skin cancers in its propensity for local, regional, and distant spread. The initial phases of cancer metastasis encompass invasion, angiogenesis, intravasation, extravasation, dissemination, and the subsequent colonization of the target organ.
Nowadays, cytostatic drugs are commonly used, however, their impact is primarily limited to restraining the uncontrolled growth of malignant cells and novel therapeutic strategies aimed at preventing invasiveness and metastasis are still lacking. Migrastatic strategies offer a unique therapeutic approach designed to prevent the formation of systemic malignant lesions and reduce cancer-related mortality. Since the migration machinery has been proven to facilitate the spread of metastases, successful migrastatic therapy could potentially decrease the necessity for high-dose cytotoxic treatments currently utilized to prevent the risk of metastatic dissemination. The optimal targets for migrastatic therapy include components essential for various types of cellular motility, such as ATP availability, mitochondrial metabolism, and cytoskeleton rearrangement.
The selected compounds from the group of pentamethinium salts (PMS) meet the criteria mentioned above. PMS bind to the inner mitochondrial membrane and inhibit mitochondrial respiration, reducing overall ATP production. They also inhibit actin polymerization, as well as the migration and invasion of tumor cells.
In this project, our aim is to identify a compound within the PMS group that exhibits the most potent antimetastatic effects in a melanoma mouse model. Additionally, we intend to conduct a comparative analysis of intratumoral and systemic (intraperitoneal) therapy strategies within a neoadjuvant approach.

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