Table of Contents
Summary
The possible role of the endocannabinoid system as a target for cancer treatment has been discussed by Skórzewska, and Gęca, in their recent paper published in Current Oncology Reports. The review highlighted the role of cannabinoids and the endocannabinoid system in advancing cancer treatment with insights from evidence-based studies.
Introduction
It is no longer news that the world is experiencing one of the highest cancer outbreaks ever. Information from the American Cancer Society shows that the US alone is projected to record over 2 million new cancer cases in 2024 while the global cancer burden is likely to hit 35 million by 2050. Although cancer-related deaths have reduced over the years, by 2050, 1 in every person you meet will be battling one or two cancer cases.
Amid this chaos, researchers are discovering new and effective solutions that can help curtail the challenges that come with cancer including managing the side effects of medications and completely getting rid of cancer cells. In a bid to find a lasting solution to this challenge that has plagued mankind for as long as we can remember, there may be hope in the endocannabinoid system (ECS).
Over the years, scientists have come to understand the ECS as a master switch that regulates several biochemical processes including pain, appetite, immune response, mental health, and more. Its close relationship with the immune system may also hold some promise in serving as a target for cancer treatment.
The connection between the ECS and cancer
Cancer cells exist in a unique community known as the “tumor microenvironment (TME)”. The tumor microenvironment (TME) is the area around a tumor, made up of different cells, proteins, and blood vessels. It helps tumors grow, spread, and sometimes hide from the immune system. The TME is directly involved in promoting the activities of tumor cells and serves as the point of communication between cancer cells to support growth and spread.
A typical TME will consist of cellular and non-cellular components that influence cancer development, progression, and response to treatment. While the TME composition varies across different tumor types, certain consistent features may include tumor cells, stroma cells, immune cells, blood vessels, signaling molecules like cytokine, growth factors, and the extracellular matrix (ECM).
The ECS was recently reported to regulate biochemical pathways important for several types of cancer including gastrointestinal, breast, and CNS tumors. Research primarily centered on in vitro studies shows how the direct activation or inhibition of cannabinoid receptors (CB) expressed in cancer cells impacts their growth dynamics and this may be an excellent target for reducing cancer progression and treating different types of cancer.
Role of the ECS in cancer microenvironment
The unique presence of ECS in tumor microenvironments has been reported to modulate the following activities;
Limiting Cell to cell signaling and communication:
Cell-to-cell signaling is crucial for tumor growth and survival. It involves the exchange of chemical messages between cancer cells and other surrounding environments including immune cells, fibroblasts, and endothelial cells. The messages are conveyed through molecules like cytokines, growth factors, and chemokines. These messages help the cancer cells suppress immune responses and support the formation of new blood vessels (angiogenesis) which is needed for their survival.
The endocannabinoid system (ECS) disrupts cell-to-cell signaling in the TME by influencing major signaling pathways controlling tumor cell survival (PI3K/Akt/mTOR pathway), tumor cell division (MAPK/ERK pathway), regulating immune response and inflammation (NF-κB pathway), immune regulation (JAK/STAT pathway), cell proliferation and differentiation (Wnt/β-catenin pathway), and production of new blood vessels (VEGF pathway).
By regulating these pathways, the ECS controls cancer cell death, inhibits cell proliferation, limits tumor growth, reduces inflammation, shifts the balance away from tumor-supportive conditions, and cuts off blood supply to the tumor.
Modulating immune cells in the tumor microenvironment
Cancer cells contain CB receptors which are responsible for modulating immune responses. When endocannabinoids bind to these receptors they can reduce the release of pro-inflammatory cytokines and promote an anti-inflammatory environment. The ECS also immune cell proliferation and differentiation, potentially increasing the number of regulatory T cells (Tregs) that suppress immune responses and protect tumors. Additionally, the ECS affects cytokine release, immune cell migration into the TME, and the phagocytic activity of macrophages, which can impact their ability to destroy cancer cells.
Conclusion
Targeting the ECS with unique cannabis-based formulations can go a long way in improving its natural ability to modulate tumor microenvironment. It is important to note that the cannabis plant has different classes of compounds like cannabinoids, terpenes, and flavonoids that have been documented to reduce the proliferation of cancer cells.
