Cesar M. Castro, M.D., Physician Investigator at Massachusetts General Hospital/Harvard Medical School, talks about a new, tumor-detecting app.

Transcription

1 Tumor-Detecting App Cesar M. Castro, M.D Cesar M. Castro, M.D., Physician Investigator at Massachusetts General Hospital/Harvard Medical School, talks about a new, tumor-detecting app. Doctor, if you could, what is the normal procedure of diagnosing tumors being benign or malignant? Cesar Castro: Sure, so whenever there s a suspicion for either a cancer or a recurring cancer, usually what happens is that a patient undergoes biopsy. The biopsy can entail a needle, or can entail something larger depending on the situation... what happens afterwards normally takes about 3 to 7 days for the pathologist to actually read and interpret the results. Since the biopsies are generally smaller than actual surgical biopsies, the pathologist really has to decide, a priori, whether to look at extra makers or look for special stains at a compromise, so given the limited amount of tissue, there s only really limited amount of makers you can look for. So how does this device change that? Cesar Castro: Well, we consider this actually to be one of the world s smallest cancer diagnostic system, in what it does rather than the 3 to 7 day turnaround time, we actually get results in 60 minutes, moreover we actually because it s so small, it actually requires less amount of tissue as well. So what happens is, we can use much smaller biopsy, like a needle for example, and look at large number of makers than you would with conventional pathology. So we did a recent study here at Mass. General Hospital where we looked at 12 cancer makers in just a small amount of tissue in a fine needle aspirate and we found it had an accuracy of 96% superior to just conventional pathology, moreover, we got the results in 60 minutes. So you can imagine that that could translate into just, not only reducing anxiety but also increasing the efficiency and accuracy of cancer diagnosis. So, basically they can go in and within the same visit and know if that tumor is benign or malignant? Cesar Castro: And that s the potential of the device, given the rapid turnaround time, you could potentially go in earlier that day and see your physician, whether

2 it s an oncologist or even your primary physician and get an initial readout. The result of whether something is suspicious and would further warrant further intervention, further more invasive biopsies -- so there are some cost and patient savings as well. And what was that study, it s 19% but tell us some numbers of how many you got right. Cesar Castro: Sure, so we first looked at 50 patients here at Mass General Hospital who had lesions that were suspicious for a cancer or a recurring cancer within the abdomen. And there was 96% accuracy so 44 out of 50 were correctly identified. Using out of 12 markers, a particular combination of four makers, we used these 4 markers on an additional 20 patients and we got 100% accuracy. Wow. Cesar Castro: So this really kind of speaks to the power of just looking at multiple cancer markers since there is no one universal cancer marker. It would be rudimentary of us to think we could find one marker for cancer since one size does not fill all, so looking at multiple markers, we can get a better sense of cancer behavior, and how these things unfold as therapy proceeds. So how does this work, I mean people see the cool tech toys performing these you know very important and timely tests? How does it all work? Cesar Castro: Right so this is I believe the world s smallest cancer diagnostic and essentially is a miniaturized version of nuclear magnetic resonance or NMR, which is kind of similar to MRI -- has the same magnetic principles of MRI, and what it does is senses so it s not actually imaging but it senses cancer markers and it relies on two main things under the software of the device, is essentially revolves around antibodies which you can consider as missiles, seeking particular cancer markers, as well as signal generating magnetic particles or nano-particles which are miniaturized particles that we actually create in our laboratory rather reproducibly. And what happens is when we have our cancer specimen we first, in a 2-step approach, first label the cancer specimen and decorate them with anti-bodies, so the antibodies specifically target the marker of interest. We then follow this with the magnetic particles or nano-particles which then in a very specific and efficient way using innovative chemistry that we also developed here, the nano-particles find the anti-bodies and essentially once it s exposed to the magnets, the nano-particles create and generate a signal that is detected through small miniaturized coils in this device, not unlike the Slinky for example.

3 So basically, the antibodies find the bad cells, and then the nanoparticles signal you to what those bad cells are? Cesar Castro: Exactly, and because of our unique chemical strategies, rather, meaning more efficient we can load more nanoparticles onto the anti-bodies, so even at low level markers, which people invariably have different levels of expression of cancer markers, even the smallest amount of cancer markers we can actually detect because we have more nanoparticles loading onto the antibodies, which latch to the cancer markers. Wow, so why go this path with Smart-Phone and the I-Pad, why use that software to do this? Cesar Castro: Well I think the biggest chasm divide between what s going on in the laboratory and clinical reality is we tried to promote its utility, trying to make sure that clinicians readily adopt the technologies, and part of that has to do with complexity, with time demands, what to do with the data, subjectivity of the data, so you know with that in mind I think we created this device to make it a portable, and also cheap the components in general overall should cost around $200 to generate, but not only is it portable and cheap, but it s also rapid. And the reason why we interface it with either a smartphone or a tablet cause we re trying to make it easier for the technical staff to just push a button so we generate data without any wiggle room for subjectivity. The data is purely quantitative and it s independent of temperature, so if whether we re doing it in Orlando, we re doing it in Boston, the data should be the same and should not be subject to interpretation. So we envision that the portability as well that there would be a use not only in academic centers but also in community hospitals and even in rural parts where you could imagine the phone communicating remotely with a central laboratory and then flagging the clinician with abnormal results. OK...and how long did it take you to develop this? Cesar Castro: So the device in itself has actually taken over a decade since its inception and as recent as 3 or 4 years ago we were only able to look at 2 to 3 markers but now really with the improvements and advances in labeling chemistries, and being able to load more nano particles onto the anti-bodies we were able to detect up to 12 cancer markers. So once we readily achieved that, we knew it was time to translate it into the clinic, it was ready for prime time because you can cure cancer in mice, you can detect cancer in mice but it s really looking at human samples and the variability inherent in a biopsy that we thought was necessary to try and really promote and query this technology. And how many cancers has it been able to detect?

4 Cesar Castro: So out of 50 patients, all cancers were caught. They all had stomach cancer? Cesar Castro: They all had cancers of a variety of types All of a variety? Cesar Castro: Solid epithelial tumors which is notoriously the more difficult cancers to treat, they for some reason either metastasized to the abdomen or they were primary cancers from the abdomen. Ok so it was variety of cancers Cesar Castro: A variety of solid epithelial when we figure those are the most difficult and resistant to therapy so anything that can make it easier to diagnose sooner rather than later as well, it would justify more invasive procedure particularly when we re dealing with these cancers I think would be warranted. So what s your hope with this, you said it s ready for prime time, but is it out there being used yet in hospital settings? Cesar Castro: Not yet, I think when you re dealing with a lot of technologies and new technologies you want to make sure particularly in the cancer realm, that you want to minimize any false positives, minimize false negatives so we are certainly trying to improve even going beyond the 4 markers, looking at other markers, trying to look at specific tumors so currently we have a study ongoing looking at ovarian cancers and trying to detect and find markers specific for ovarian cancers. And we also envision even a step beyond diagnosis actually looking at pathways since this is such a real time, we get a 60 minute readout of the cancer, you get a snap shot of its behavior at that time. So if we can actually look at the pathways and interrogate the pathways, and these pathways are essentially the growth routes that are necessary that cancers take in order to promote its survival, in order to promote its metastases so we can actually try and look at whether certain pathways have been interrupted in the presence of a drug for example. So it s almost like a real time drug assay of a patient s biopsy and if certain pathways are hit and certain pathways are not, you can triage patients to either particular clinical trials, or particular therapeutic strategies, so that s where you go the next step. And it s this proof of concept that we ve established that we can look at human samples with all its inherent complexities, do it fast, do it accurately and now want to take it to the next step and try really to interrogate the biology of tumors.

5 So how long before you think this is widely available, this has to be updated proof and all the steps as well? Cesar Castro: So it s probably going to take a while, it s going to take a matter of 5 to 10 years before we see it in more wide spread use. I think the appeal of its low cost given the current economic climate really speaks for one of these kind of technologies and we hope that it also stimulates other groups and other cancer centers to try and push low cost, rapid accurate technologies albeit the need for more invasive, potentially more dangerous patient interventions. So we hope it does have to go through more testing, the rigmarole of validation and also approval of the device platform, but just given the excitement and the early findings that we see, and how it s being embraced by the scientific community, we see there s a vast potential for this type of technology. END OF INTERVIEW This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters. If you would like more information, please contact: Cesar M. Castro, MD Physician Investigator Massachusetts General Hospital/Harvard Medical Center Boston, MA Castro.Cesar@mgh.harvard.edu Sign up for a free weekly on Medical Breakthroughs called First to Know by clicking here.

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