What is BostonGene? What is Next Generation Sequencing (NGS)? How do these reports help us to better understand new treatment options currently available for Fibrolamellar Carcinoma?
To answer these important questions, we need a a little background information. We know that all cancers have a mutation or genetic defect in their DNA, usually many such defects. This is called a “somatic mutation” or “tumor mutations.” It’s important to know that this does not mean there is a mutation in the non-tumor cells and normal cells. The mutation cannot be passed on to other children, it does not come from either parent. In fact, even if the person has an identical twin, they would not have this ‘somatic mutation.’ On the other hand, a mutation that is in every single cell in your body, for example in Down Syndrome (thinking of my amazing daughter right here!), every single cell has an extra chromosome twenty-one. This is called a “germline” mutation, from the Greek word for “seed.” A germline mutation can run in families or be just a one-time event. Very rarely do we see germline mutations in FLC.
When we test a tumor for Next Generation Sequencing (NGS) we are trying to find the mutations that show us where and how the tumor might be vulnerable to guide us in choosing the most rational treatment. These mutations typically “overexpress” a bad protein that is driving or protecting the cancer. There are many NGS being used today, such as Foundation One, Tempus, Caris and the many that are done ‘in-house’ at the larger universities. However only BostonGene has a specialized panel of mutations to hunt for that are made just for FLC – not a generic panel for any cancer – and, most importantly, examines the ‘micro-environment’ of the tumor.
More background: The microenvironment is what is sounds like, the microscopic (way too small to see without a very powerful microscope) environment of cells and proteins that surrounds tumor cells and either tries to kill it (the immune cells such as T-cells and B-cells) or, unfortunately, tries to protect the tumor (such as ‘myeloid derived immune suppressor cells). As Tom Stockwell aptly explains it: the tumor microenvironment is the castle protecting the evil Monarchs made up of the mote, the walls, soldiers and the archers whose jobs are to protect the King or Queen (your tumor) at all costs. To destroy the evil rulers we need to also understand and attack the soldiers protecting them.
Several years ago, FibroFighters entered a partnership with BostonGene to develop a specific understanding of the mutations that help drive or protecting FLC and how they are different from other cancers, thus leading us to new treatment ideas. Here are two examples: your tumor may ‘overexpress’ a protein called interleukin-6 (IL-6) that helps to protect and promote your cancer. We have seen IL-6 overexpression on many BostonGene tumor portraits and recommend a non-cancer drug called Tocilizumab (Actemra). Thus far 29 FLC patients have used this medication and we have seen it offset cytokine induced checkpoint therapy storms and, in several cases, reduce tumors. Second, in the microenvironment, your tumor may show an excess of myeloid derived immune suppressor cells (MDSCs). MDSCs makes up one of the soldier groups protecting the tumor and their job is to prevent your natural immune system, systemic treatment, or anti PD-1 immune therapy from delivering successful assaults upon the FLC tumor. We can target these cells with one of the drugs designed to reduce their levels using low dose gemcitabine (Gemzar), capecitabine (Xeloda), or even Retinoic Acid (Vitamin A).
Please see the example report at the bottom of this page.
To date we have collected more than 70 BostonGene fibrolamellar specific portraits and we have begun to see patterns emerge advancing our knowledge of FLC and how it behaves differently in some patients and getting us one step closer to establishing better and more targeted treatments.
Keep the hope. Stay positive. Sending infinite love.
Dr. Kent