Glioblastoma, ecDNA & Targeted Therapy - The Verhaak Lab at Yale School of Medicine

Transcript

• 00:06Typically DNA is on linear strands.
• 00:08So you have 46 chromosomes.
• 00:10Each of those 46 chromosomes is a linear strand of DNA.
• 00:14However, in some cancer cells,
• 00:15what we found is that there are small pieces of circular DNA,
• 00:19and these are called extra chromosomal circular DNA amplification, or ecDNA in short.
• 00:24The presence of DNA enables cancer cells such as glioblastoma cells or brain cancer cells
• 00:29to adjust to challenges in their microenvironment.
• 00:33For example, the presence of ecDNA enables those cancer cells
• 00:37to deal with the toxic effects of radiation therapy or chemotherapy
• 00:41or any other therapy for that matter.
• 00:49Our lab is a brain cancer lab.
• 00:51We are dedicated to developing therapies
• 00:53to better treat glioblastoma and glioma patients.
• 00:57Glioblastoma is a grade four brain tumor.
• 00:59It's the most common malignant brain tumor in adult patients.
• 01:03It's a devastating tumor type.
• 01:04Patients that are diagnosed with this kind of cancer
• 01:07often have a very short lifespan following diagnosis.
• 01:10This is a tumor type that really has not seen any
• 01:12progress in clinical treatments in the past 30-40 years
• 01:15and we are very motivated to change that.
• 01:24My lab has traditionally done a lot of profiling,
• 01:27which means that we take a tumor sample from a patient
• 01:29and generate lots of data from this single tumor,
• 01:32sometimes billions of data points,
• 01:34and then we use computational data science approaches
• 01:36to make sense of those data sets.
• 01:39Now we are in a phase where we're trying to take what we've learned
• 01:43and do functional experiments,
• 01:46where we can test hypotheses that are derived from our data science analysis
• 01:50and turn those into targets
• 01:53and once we have targets, which is a stage where we are now, we have targets
• 01:57we want to turn that into,
• 01:58can we now develop small molecules or other treatment modalities
• 02:02that aim for those targets.
• 02:09Anybody who has had cancer or who knows somebody that has been treated for cancer,
• 02:12knows that the side effects are often very challenging
• 02:16and sometimes lead the patient to no longer be able to take a certain therapy.
• 02:20For example, many chemotherapies are so toxic,
• 02:23the patient gets so sick that treatment has to be discontinued.
• 02:26So targeted therapy is a way to treat patients with very high efficiency.
• 02:31You're really trying to only hit the cancer cells
• 02:33and leave the other cells in your body alone,
• 02:36and thereby minimizing all those toxic side effects.
• 02:39Our strong motivation is to develop these molecules,
• 02:42make them safe to use in humans,
• 02:44and then put them into phase zero, one, two, or three trials,
• 02:47and ultimately approval by the FDA.
• 02:51I work closely with radiation neuro-oncolology
• 02:53and neurosurgery and pathology and radiology.
• 02:56Glioblastoma is disease that no individual is ever going to a cure.
• 03:00This really has to come from collaboration,
• 03:02open science, to together do better for these patients.