Neurosurgeon Daniel Cahill has experienced the anguish that a Glioblastoma diagnosis can bring. Patients are often brought into the emergency room suffering excruciating pain from seizures or migraines, because of which an MRI is typically performed.

An MRI is a brain scan that isolates the tumor and reveals information about its size and location. He also mentions how the other option for patients is a biopsy, which involves tissue extraction and can provide insight into tumor specific biomarkers to specialize treatment. However, biopsies can be traumatic and so aren’t performed as frequently.

The initial care and diagnosis are carried out by a neurosurgeon, but the radiation oncologist and neuro-oncologist subsequently join the team. While it may seem like only one doctor is caring for the patient, in reality, a team is working nonstop behind the scenes to slow tumor progression.

David Begnaud was diagnosed with Glioblastoma and told he had just months to live. However, he surpassed the doctor’s predictions and emerged as a fighting force against the tumor. As a patient facing over a 90% mortality rate, he details his gratitude to be one of the few who overcame this diagnosis.

After undergoing extensive surgery during his recovery journey, he recalls his son being placed on his lap: “He looked me in the eyes and he was smiling and I looked at him and I decided right there, I wanted to show him how to live.”

To many patients, family is their only solace through these life-altering times. His wife Melissa reflected on what seemed like at the time their last trip to North Carolina for Begnaud’s 29th birthday, saying “I remember taking a picture of that cake, thinking that this will probably be his last birthday.”

She captured that picture in her mind, cherishing one of the few moments of peace with her husband. But it wasn’t his last birthday, and Begnaud would go on to celebrate many more. Today, he shares his story in the hopes that patients can be inspired to fight on, no matter how tough the struggle is. But for the other over 90% of people, their fight doesn’t last long.

However, a new drug has entered the market with the potential to break the survivability hurdle.

Selinexor, developed by Karyopharm Therapeutics, can cross the blood-brain barrier (BBB) to kill cancer cells, a challenge that has blocked the utility of many other chemotherapy drugs.

The BBB is an outer protective layer of the brain that shields it from toxic substances in the blood, but it also blocks many chemotherapy drugs. However, Selinexor has broken these constraints.

Originally developed to treat multiple myeloma and select forms of lymphoma, researchers are now hopeful of Selinexor’s potential to treat Glioblastoma since it inhibits the XPO1 protein, overexpressed in many cancers including Glioblastoma.

XPO1 is a nuclear export protein that transports major tumor suppressor proteins (TSPs) out of the nucleus to the extracellular area called the cytoplasm. If XPO1 is blocked, cells cannot survive.

Cancer cells are extremely dependent on XPO1, so researchers looked to block XPO1 through the use of Selinexor which also damages cancerous cells’ DNA, and when combined with other forms of chemotherapy, may slow recurrent Glioblastoma growth.

Selinexor must go through rigorous rounds of testing to get FDA approval for use on Glioblastoma, but the approval process is lengthy.

Each clinical trial must be backed by a sponsor, which are usually pharmaceutical companies, government agencies, or healthcare organizations. They must then go through meticulous stages of animal testing before applying to test on humans, with even more stringent protocols before applying for FDA approval.

Researcher and Oncologist Dan Vogl, who runs trials on Selinexor’s effectiveness at treating Multiple Myeloma, commented “Selinexor is exciting because it works differently from every other type of medicine used to treat cancer,” and it unlocks doors that were previously shut.

Vogl became involved in the clinical trials for Selinexor after the idea had been initially developed and tested in patients with Multiple Myeloma, not Glioblastoma. From there, it was determined that Selinexor showed the most promise to combat Multiple Myeloma.

However, before these trials on patients happen, researchers must undergo a rigorous process. After first developing the idea of how a medicine could potentially solve a problem, a molecule must be designed and tested in the laboratory to measure its intended effect.

Then, medicinal chemistry, which involves testing whether that molecule can be administered as a pill or injection, has to be tested to determine if the body immediately breaks it down before the drug has its intended effect.

In the case of Selinexor, it can be administered through a pill. This optimized molecule is then tested on at least two different animals, one of which has to be a primate to more accurately screen potential dangers before advancing it to human trials. After that, the human trials are cleared to begin.

Cancer medicines are usually given in minuscule doses to about 1-3 people with late-stage cancers. If they exhibit progress, the dosages are slowly increased until they cause unbearable side effects. The phase 1 trial aimed to determine the optimal dosage of Selinexor; however, many people were experiencing debilitating side effects that hindered the early success of Selinexor.

Vogl details how when patients were given 80 miligrams two times a week, they experienced severe fatigue, a loss of appetite, low blood counts, nausea, and diarrhea among other repercussions. But when that dosage was lowered to between 40-80 miligrams once a week, the side effects receded.

During the phase 2 trial, which gave the optimal dosage to many patients, halfway through the study a new and revolutionary medicine called Dexamethasone to treat Multiple Myeloma became available. The patients in this study had only been exposed to old treatments, but now because they were on the new drug, a new study had to be constructed which took into consideration Dexamethasone.

This advancement set their progress back, as researchers had to conduct a new set of trials. Whereas patients had no other options beforehand and thus looked to Selinexor, the “definition of no other options changed because another option had arrived” said Vogl.

After human trials have been run multiple times, often a process that takes years on end, researchers can apply for FDA approval.

The FDA takes its responsibilities seriously to make sure drug companies have proven to make sure treatments are safe and effective for individuals. They hold researchers to rigorous standards of evidence in order to prove they have met these requirements.

In the case of Selinexor, original approval was based on how many people had their Myeloma shrink. Half of the participants got Selinexor and half didn’t, in addition to a standard myeloma treatment. The people who were administered Selinexor had more control over their Myeloma, which eased FDA approval.

After a drug is approved by the FDA, doctors can prescribe it for any type of cancer. However, insurance doesn’t cohesively cover this, thus the treatment can be incredibly expensive.

If the trials are successful, sometimes doctors will convince insurance companies to cover the drug before the FDA approves it. Additionally, sometimes the company that makes a medicine will agree to prescribe it for free, as when the approval comes they can make money.

Selinexor varies from other drugs, particularly in its effectiveness in combating many types of cancers. However, researchers are still faced with the question of how the side effects will play out once Selinexor targets the XPO1 protein in patients with Glioblastoma.

Dr. Vogl details his hope with Selinexor to work long-term in treating both Multiple Myeloma and Glioblastoma, as many drugs stop working after a set amount of time with these types of cancer.

One of the biggest problems with the cancers that Selinexor is trying to cure is that they are not curable. Thus, to quote Dr. Vogl once again “new and different is really important.”

As trials for Glioblastoma continue to progress, Selinexor will undergo more rigorous processes for further approval. However, this miracle drug is currently the guiding beacon to many cancer patients’ lives.

In the words of Dr. Vogl, “I have some patients who are alive today because they were able to get Selinexor to keep their cancer under control.”