Many types of cancer are capable of spreading or metastasizing to the brain including lung, breast, melanoma and colorectal cancer. There is no cure for metastatic cancer of any type, but treating brain metastasis poses unique challenges.
In two recent review
articles, President-Elect of the Metastasis
Research Society, Dr. Dihua Yu, and colleagues discuss what is currently known
about the complex biology of brain metastasis and which therapies or strategies
are most promising.
The brain is unique. It supports and preserves neuron functions with
a network of specialised cells including astrocytes and microglia, and is
protected by the ‘blood-brain barrier,’ which separates the brain from the circulating
bloodstream.
So how do cancer cells
survive in the foreign environment of the brain and grow into metastatic brain
tumors? Simply put, these cells are endowed with aggressive traits that enable
them to cross the blood-brain barrier, escape recognition by anti-cancer immune
cells in the brain, use the existing brain vasculature for nourishment, and they
can even ‘educate’ other normal cells in the brain to support their growth and
survival.
Unfortunately, the aggressive
traits of metastatic brain tumors can also make them resistant to standard
systemic cancer therapy. In addition, more than 80% of patients with metastatic
brain cancer already have multiple metastatic tumors at the time of diagnosis,
making them ineligible for surgery.
Dr. Yu and colleagues note
that the support of cancer growth in the brain by surrounding resident brain cells
is a major contributor to therapy resistance.
Therefore, counteracting the ability of metastatic cancer cells to communicate
with resident cells of the surrounding microenvironment should increase the
clinical benefit of standard therapies.
It may also be possible to
target the unique metabolic needs of brain metastatic cancer cells
therapeutically. Metastatic cancer cells must alter their
metabolism to survive and grow in the brain.
For example, cancer cells can adapt to use neurotransmitters of the brain
as metabolites. Cancer cells may also
become addicted to certain metabolites that could potentially be limited. But,
the concept of targeting metastatic cancer cell metabolism isn’t ready for
primetime in the clinic because many aspects of these molecular pathways still
need to be clarified.
Much insight in the field of
brain metastasis is expected to come from studies with preclinical models that
recapitulate the entire metastatic process, and the intimate interactions between
tumor cells and cells within the tumor microenvironment (cells in the area
surrounding the brain tumor). Moreover, advancements in neuroimaging techniques
are providing new tools for live imaging.
This technology is increasing our understanding of metastasis in
experimental models and improving diagnostics in patients.
The extensive characterization
of genes (genomic characterization) and molecules that are transcribed from
genes to create proteins (transcriptomic characterization) in metastatic tumors
isolated from patients is also providing clues to how tumor cells that
metastasized to the brain differ from normal cells and from each other. Tumor cells may be heterogeneous (different)
and endowed with different molecular features and abilities even if they are
within the same tumor.
With this information, new
hypotheses on the molecular mechanisms that orchestrate the establishment and
progression of brain metastases are developing and creating new opportunities
to find therapies that target a specific molecular feature of brain metastatic
cancer cells.
In addition to targeted
molecular therapies, immunotherapies are emerging as a potentially efficacious strategy
for the treatment of brain metastases.
These therapies don’t target brain metastatic cancer cells themselves,
but instead enhance the function of immune cells to suppress tumor growth. Clinical investigations are now demonstrating
that the ability of immune checkpoint inhibitors to effectively inhibit metastatic
brain tumors is similar to their ability to treat metastatic tumors outside of
the brain. However, they could produce
severe side effects. This concept is
explored in another article here.
Despite encouraging progress
in this field, the clinical management of patients with brain metastases is still
challenging and financial support for studies on metastatic cancers is limited.
Further effort is required and active cooperation among biologists,
neuroscientists and oncologists is the key to targeting metastatic cells early
and from different fronts.
Source Articles:
About the Metastasis Research Society
The Metastasis Research Society (MRS) is a 31 year-old,
non-profit, international professional society for researchers, clinicians,
members of industry, and entrepreneurs who are dedicated to solving the problem
of cancer metastasis. The mission of the MRS is to support progressive
research on any processes fundamental to metastasis. This includes supporting
the exchange of information between all stakeholders in metastasis research and
treatment via conferences, networking events, webinars, and the two official
journals of the society (Clinical and Experimental Metastasis and Cancer
and Metastasis Reviews). We also strive to educate the public about
metastatic cancer, and raise awareness about the funding discrepancy for
metastatic research worldwide.
We encourage you to join our efforts and support metastatic cancer research and metastatic patient education globally by becoming an MRS member. Click here to view membership categories and benefits, and join today. Follow the MRS on Facebook and Twitter for up-to-date metastasis-related news. Email metastasis.research@gmail.com for more information.
We encourage you to join our efforts and support metastatic cancer research and metastatic patient education globally by becoming an MRS member. Click here to view membership categories and benefits, and join today. Follow the MRS on Facebook and Twitter for up-to-date metastasis-related news. Email metastasis.research@gmail.com for more information.
