<p>You may or may not be familiar with the Tragically Hip, but north of the border, this band is a big deal. More specifically, ex-frontman Gord Downie is something of a national treasure, and his tragic death in 2017 from brain cancer was hard to swallow.</p> <p>Throughout 2016, Downie and the rest went on tour to play their final dates together as they raced against the clock of his terminal diagnosis, with over 11 million Canadians viewing the broadcast of his final show. He was 53 when he passed.</p> <p>Gord died from glioblastoma multiforme (GBM), and his rapid decline was nothing out of the ordinary for this disease. It’s the most aggressive type of brain cancer, and most patients don’t make it past 18 months of their diagnosis. </p> <p>This deadliness is why the disease is referred to as “The Terminator”, and researchers have been repeatedly frustrated in their efforts to outsmart it. Work is ongoing, however, and some new leads are offering hope to patients and families — if even just to secure some extra time.</p> <h3>An overview of GBM</h3> <p>If there’s one good thing that can be said about GBM, it’s that it’s rare (although it is the most common brain cancer in adults). </p> <p>It starts in cells called astrocytes, whose purpose is to support nerve cells and transport nutrients to them. Numerous mutations in astrocytes are linked to the disease since they disrupt the cell’s ability to regulate itself, leading to uncontrollable growth. It remains an open question as to what causes this chain of events. </p> <p>Since the brain is the command centre of the body, cancer in a certain area can inhibit or interfere with the functions it controls. For example, it might trigger in an area that controls movement, and the symptoms may therefore manifest as a feeling of weakness in your arms.</p> <p>As the tumor progresses and more space is consumed, the pressure inside the skull increases. Some symptoms manifest because of this, with examples including:</p> <ul> <li>Persistent headaches</li> <li>Blurry vision</li> <li>Memory issues</li> <li>Vomiting</li> <li>Low appetite</li> <li>Personality and mood changes</li> <li>Seizures</li> <li>Speech issues</li> </ul> <p>Both the condition itself and the available treatments can wreak havoc on the brain, and this can result in issues related to cognition, mood, behavior, and more. Some compare the effects to a loss of identity given how profound it can be on a person’s mind and personality.</p> <p>The typical treatment for GBM is a combo of surgery, radiation therapy, chemotherapy, and sometimes specialized electric devices, all of which can help to slow its progress. It almost never amounts to a cure though.</p> <figure><img style="max-width: 100%;" src="https://cdn.storymd.com/optimized/LA18k7uQq5/original.jpg" alt /> <figcaption>Glioblastoma multiforme - MRT T2 axial. <em>Source: Hellerhoff/Wikimedia</em></figcaption> </figure> <h3>“I’ll be back…”</h3> <p>The Terminator is nothing short of insidious. </p> <p>First, many chemo drugs can’t cross the blood–brain barrier to attack the cancer. Nearly a decade ago, a breakthrough came with a new chemo drug called temozolomide that could cross the barrier. A subset of patients responded to the medication and modestly lengthened their lifespan, but for many patients the drug didn’t garner a response.</p> <p>Second, as the tumor expands, it spreads throughout the brain as if it had “tentacles” that force their way into pockets of nearby tissue. It then embeds itself in the brain in such a way that doctors can’t simply go in there and remove it surgically — even if you caught it before it had spread out, the tumors tend to recur and continue digging deeper into the brain.</p> <p>Third, scientists are learning that no two cases of GBM are quite the same. Though you may have the same diagnosis, things can be quite different at the cellular level from patient to patient. </p> <p>Making things even crazier is that individual cancer cells within one patient’s tumor can be significantly different again, so a single-target therapeutic isn’t necessarily going to work. The speedy growth and accumulation of different mutations in different cells is part of GBM’s dynamic power.</p> <h3>Turning the hunter into the hunted</h3> <p>Despite GBM’s grim outlook, scientists are determined to conquer it. New therapies are being tinkered with across different disciplines, and the results have been impressive.</p> <p>Take Selinexor, for example. This anti-cancer drug was previously given the green light by the FDA to treat multiple myeloma and large B-cell lymphoma. A recently published Phase II clinical trial with GBM patients showed that in almost one third of them, the tumor shrank. </p> <p>Another area of interest is chimeric antigen receptor (CAR) cellular therapies. Still a work in progress, researchers have found viable leads for this approach in both animal models and small trials with humans. </p> <p>Remember the blood–brain barrier problem? Some of the CAR therapies tested so far have been able to cross it as well as reduce the tumor’s size. One patient even made it to 36 months with an experimental CAR treatment. </p> <p>In a 2019 study, researchers “reverse engineered” GBM stem cells and unearthed several potential leads for new treatments. Using a powerful gene-editing tool known as Crispr-Cas9, they were able to hone in on around 400 genes that could be responsible for driving the disease. </p> <p>Viral gene therapy could also break the impasse with GBM. These therapies use modified viruses to deliver drugs that carry specific DNA sequences with therapeutic qualities into cells. GBM cells’ “natural sensitivity” to viral infection means that the therapy marks a “promising prospect” in treating the disease, according to one paper. </p> <p>Next, there’s immunotherapy. One team of researchers observed a median overall survival of 41.1 months in GBM patients using this technique. Another team at Northwestern University discovered a new biomarker that could identify patients eligible for immunotherapy, and the treatment reportedly extended lifespans for 20–30% of patients.</p> <p>Lastly, there’s GBM Agile, a global initiative designed to help patients to receive multiple treatments simultaneously and reduce the number of placebos used in trials. The program connects patients with new drugs being trialed that fit their biological profile; this way, patients have the chance to capitalize on experimental treatments that could benefit them while also making the research process more efficient.</p> <blockquote> <h2>Short Reports</h2> <ul> <li>A rather bizarre spate of brain cancer diagnoses including glioblastoma have been connected to a single school in New Jersey. Over 100 graduates of the school were diagnosed with brain cancer in the last 30 years, which is highly unusual. Multiple public bodies including the CDC are investigating the situation to confirm whether there is an actual case cluster happening, and if so, what could be the cause.</li> <li>In Canada, a study published this year found that people living close to wildfires have a significantly increased risk of developing multiple cancers. The researchers reported that people who lived within 50km of wildfires over the last decade have a 10% higher risk of brain cancer. While they were quick to emphasize that we can’t jump to conclusions about a causal effect since it’s a lone study, further work is needed to explain the result conclusively. </li> </ul> </blockquote><h2>More on Glioblastoma</h2><ul><li><a href="https://soulivity.storymd.com/journal/rjykex51yw-glioblastoma" target="_blank">Glioblastoma: Symptoms, Treatment, Prognosis</a></li><li><a href="https://soulivity.storymd.com/journal/nwl9xyxiew-brain-and-spinal-cord-tumors" target="_blank">Brain and Spinal Cord Tumors: Types, Symptoms, Treatment</a></li><li><a href="https://soulivity.storymd.com/journal/dmqnbr4uem-gliomas" target="_blank">Gliomas (Glial Cell Tumors): Types, Symptoms, Treatment</a></li></ul>