What if you get diagnosed with cancer? What if your beloved family member, partner, or friend gets diagnosed with cancer? The news may fill you with fear and despair. Particularly, what if you get diagnosed with glioblastoma (GBM)? GBM is the most aggressive type of brain cancer with an average overall survival time of 15~21 months after the first diagnosis. Moreover, GBM patients’ 5-year survival rate is less than 7%, one of the lowest among all cancers. Although treatment for other cancers is prevalent, current treatment options for GBM are ineffective and inevitably result in relapse and death. Such devastating facts would fill you and your loved ones with despair. However, what if you learned that a new treatment could stop the progression of GBM and significantly increase your chances of survival? What if you heard that you could manage your cancer with this new treatment? Dr. Nikos Tapinos and I at Brown University are developing this new treatment, one that would bring hope to you and your loved ones.
What’s Drug discovery process?
How does a new treatment get discovered? The drug discovery process is divided into three steps:
1. Drug Discovery and Development.
2. Preclinical Research
3. Clinical Research.
During Step 1, researchers elucidate the mechanisms of disease progression, which leads to the discovery and development of a treatment that inhibits the disease process. Once a potential treatment candidate is selected, this candidate will go to Step 2 where researchers test the safety, side effects, how the drug affects the body, how the body responds to the drug, and so forth. Preclinical research also requires a larger testing setting monitored by a third party (e.g. the FDA in the US) to verify functionality…. Once this treatment candidate is determined to be safe enough, then this treatment will go to Step 3, Clinical Research, where the efficacy of this treatment in human patients will get tested. This entire process takes about 10-15 years for a single treatment candidate to become publicly available.
In order for us to develop a new treatment, however, we need to identify why current treatment is not effective for GBM (in other words, what part of the tumor/cancer current treatment can and cannot treat).Current treatment for GBM is majorly composed of surgical removal, chemotherapy, radiation therapy, or a combination of those. Each treatment has its own disadvantage that makes it ineffective for GBM. Surgical removal cannot perfectly remove GBM and leaves the remaining GBM cells in the brain. Chemotherapy is normally administered to treat these remaining GBM cells, however it is challenging to specifically target the distributed GBM cells without killing the surrounding healthy normal cells. Radiation therapy is a powerful treatment, but has similar difficulties as chemotherapy since shooting lasers specifically at all the cancer cells without damaging the surrounding healthy normal cells is impossible. As seen in these cases, all the current treatment approaches have huge clinical challenges, which makes GBM currently impossible to treat. In our research, Dr. Nikos Tapinos and I are at Step 1 (Discovery and Development), and we have been investigating the mechanism of GBM metastasis, the development of malignant growth beyond the initial cancer site, and testing the efficacy of our treatment candidate in test tubes and animals. Our challenge is to develop an approach that overcomes the surgical disadvantage.
To address this challenge, Dr. Nikos Tapinos and I are developing a new technique for GBM therapy: GliaTrap. GliaTrap basically functions just like a Japanese cockroach trap “Gokiburi hoihoi”, a container that houses foods to attract cockroaches and drugs to kill the attracted cockroaches. With GliaTrap, cancer cells are the cockroaches. GliaTrap uses a biocompatible material called hydrogel, like the container of the Gokiburi hoihoi, to house foods and drugs that lure and kill cancer cells. Food for cancer cells is called a chemoattractant, and GliaTrap uses this molecule to lure the residual GBM cells post-surgery to the vicinity of the empty space, just like a cockroach trap uses foods to attract cockroaches. Once these cancer cells are attracted to GliaTrap, GliaTrap uses an anti-tumor agent to kill those cells at the vicinity of the empty space without causing significant damage to healthy cells, just like cockroach traps use drugs to kill the cockroaches. GliaTrap will be able to eliminate the remaining cancer cells from the surgery to prevent tumor recurrence.
GliaTrap can utilize not only anti-tumor agents, but also lure/use the body’s natural immune cells. Anti-tumor agents in GliaTrap can be replaced with immune cell activators, a molecule that boosts the ability of immune cells to attack cancer cells, in hydrogel. GliaTrap’s chemoattractant potentially can attract immune cells, not only cancer cells, and these immune cells get boosted by activators to attack cancer cells, just like cockroach trap’s food can attract spiders, not only cockroaches, and these spiders get boosted by another energy drink to attack cockroaches.
What if GliaTrap’s chemoattractants don’t attract immune cells, just like cockroaches foods might not attract spiders? Anti-tumor agents can get replaced by artificial immune cells. Basically, immune cells are pre-placed in hydrogel and wait for cancer cells to come to the hydrogel and attack those cancer cells who invade the hydrogel, just like spiders can be placed in a container and wait for cockroaches to come to the container and attack those who invade the house.
As seen in these examples, GliaTrap can serve as a new treatment delivery method in concert with surgical removal and chemotherapy. GliaTrap combines targeted capture and drug release to increase therapeutic efficacy and safety by selectively killing the cancer cells that surgical removal and chemotherapy might miss. As a result, GliaTrap will magnify the survivability rate of GBM patients.
Looking forward, GliaTrap can potentially be applied to other types of invasive cancers that don’t have effective current treatments and that have a similar treatment protocol such as pancreatic cancers. Pancreatic cancers have a similar treatment protocol – surgical removal followed by chemotherapy, radiotherapy, or a combination of those. . Pancreatic tumors can exhibit different genetic and physiological profiles from GBM – , each individual cell has their own profile. Because of this difference, the response to chemoattractants varies as well; some cancer cells respond to chemoattractant A, but other cancer cells do not. Just like human beings have a preference for foods and not all people like one kind of food. GliaTrap can be implanted into the empty space created by removal of pancreatic cancer cells, and perform similarly to GBM treatment by choosing an optimal chemoattractant for pancreatic cancers. To ensure the coverage of capturing cancer cells, genetic profiles of cancer cells can be investigated and optimal chemoattractants can be used. This is similar to restaurants performing marketing research to figure out what customers prefer and deciding what foods to provide based on the results of marketing research. Chemoattractants and therapies can be selected based on the genetic profiles of cancer patients, and GliaTrap can be tailor-made for each patient. With continued effort, GliaTrap will become a platform for combination therapies for various types of cancers and make personalized medicine come true.
GliaTrap has great potential, but comes with many challenges and needs further study to prove its effectiveness and safety before it can be widely used by cancer patients
. Despite all these drug discovery challenges, we commit ourselves everyday to research and strive to perform experiments that lead to the development and application of GliaTrap. We aim to develop GliaTrap to boost the efficacy and safety of extant cancer therapies. We hope that GliaTrap will increase the survival rate while maintaining the quality of cancer patients’ lives. GliaTrap will change the paradigm of treatment selection in the field of oncology and catapult the field of cancer medicine forward. Ultimately, we hope to create a society where patients and their loved ones will no longer view any kind of cancer diagnosis as a death sentence, but rather as a challenge that can be overcome with the right treatment. We believe that GliaTrap will be the right treatment for patients, helping remove the fear of a cancer diagnosis, and bring hope to those patients and their loved ones.
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