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50 Years of Cancer Progress: Radiation Oncology

February 10, 2025
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  • 00:00Funding for Yale Cancer Answers
  • 00:02is provided by Smilow Cancer
  • 00:04Hospital.
  • 00:06Welcome to Yale Cancer Answers
  • 00:08with the director of the
  • 00:09Yale Cancer Center, doctor Eric
  • 00:11Winer.
  • 00:12Yale Cancer Answers features conversations
  • 00:14with oncologists and specialists
  • 00:16who are on the forefront
  • 00:17of the battle to fight
  • 00:18cancer.
  • 00:19This week, it's a conversation
  • 00:20about radiation oncology with doctor
  • 00:23Peter Glazer.
  • 00:24Doctor Glazer is the Robert
  • 00:25E. Hunter Professor of Therapeutic
  • 00:27Radiology
  • 00:28and Professor of Genetics and
  • 00:30chair of the department of
  • 00:31therapeutic radiology at the Yale
  • 00:33School of Medicine.
  • 00:35Here's doctor Winer.
  • 00:37Can you just tell us
  • 00:38a little bit about yourself?
  • 00:40How is it
  • 00:42that you came to be
  • 00:43a radiation oncologist?
  • 00:45I'm a
  • 00:47physician scientist with an MD
  • 00:49and a PhD in genetics,
  • 00:51and as you mentioned,
  • 00:52my medical specialty is in
  • 00:53radiation oncology.
  • 00:56And my research focuses on fundamental
  • 00:58cancer biology and
  • 01:01development of translational
  • 01:02research opportunities.
  • 01:05I got started in the
  • 01:07field because of a strong
  • 01:08clinical interest in oncology,
  • 01:11and in taking care of
  • 01:12cancer patients, and that was
  • 01:13coupled with a growing research
  • 01:15interest in the field of
  • 01:17DNA repair, which is how
  • 01:18cells fix their DNA.
  • 01:21And that's an important topic
  • 01:22in the field of radiation
  • 01:23oncology.
  • 01:25Can you just
  • 01:27tell us a little bit
  • 01:29about
  • 01:30radiation as a treatment,
  • 01:33both in terms of how
  • 01:34it's delivered, or
  • 01:37I should say the different
  • 01:39ways in which it can
  • 01:40be delivered.
  • 01:42And then we'll explore
  • 01:44some other aspects of radiation.
  • 01:46Sure. Radiation
  • 01:47oncology is the medical specialty
  • 01:50that uses focused x rays
  • 01:51to treat cancer
  • 01:53because of their ability to
  • 01:54kill cancer cells.
  • 01:56And early medical applications of
  • 01:58radiation were based on radioactive
  • 02:00materials like radium
  • 02:01that were discovered by
  • 02:03Marie Curie, because early on
  • 02:05it was found that radiation
  • 02:06causes tumors to shrink.
  • 02:09Later on, other isotopes like
  • 02:10cobalt, iridium,
  • 02:12and others were identified and
  • 02:14developed,
  • 02:15and some are used for
  • 02:16a type of treatment called
  • 02:17brachytherapy, which involves placement of
  • 02:19radioactive
  • 02:20sources
  • 02:22in close proximity to a
  • 02:23tumor as is frequently done
  • 02:25for cancers of
  • 02:28the gynecologic
  • 02:30tract in women.
  • 02:31So a device is actually
  • 02:33put in and it gives
  • 02:34off radiation
  • 02:35while it sits
  • 02:37essentially near or within somebody.
  • 02:39It dwells next to the tumor.
  • 02:45It's put in a
  • 02:46surgical procedure, and then it's
  • 02:48removed after a specified time.
  • 02:51And in some other
  • 02:53approaches, isotopes are
  • 02:55injected systemically for special applications
  • 02:58usually linked to a carrier
  • 02:59like an antibody.
  • 03:02When X rays were first
  • 03:04developed, it was known that
  • 03:05they could be generated by
  • 03:06cathode ray tubes, but
  • 03:08that was low energy and
  • 03:09had drawbacks. So after World
  • 03:11War II, a major advance
  • 03:12was the development of technology
  • 03:14to
  • 03:15accelerate electrons
  • 03:18at high voltage into a
  • 03:19medical target to
  • 03:21generate high energy x rays
  • 03:22or photons.
  • 03:23And that was the birth
  • 03:24of the linear accelerator or
  • 03:26LINAC.
  • 03:28And this allowed for treatment
  • 03:29of deep seated tumors in
  • 03:30the body with sparing of
  • 03:32superficial
  • 03:33tissues.
  • 03:35And it seems to me that
  • 03:36it was the case many
  • 03:37years ago
  • 03:39that radiation oncologists would take
  • 03:41an x-ray,
  • 03:43just a standard x-ray that
  • 03:45might show, for example, in
  • 03:46the chest
  • 03:47a lung cancer.
  • 03:49And
  • 03:50in what now seems like
  • 03:52a pretty crude manner,
  • 03:54they would just draw around
  • 03:56that tumor and then aim
  • 03:58the beam
  • 04:00at the tumor. Is that
  • 04:02basically right?
  • 04:04Yes, early on
  • 04:05the treatment machines were
  • 04:08were limited in
  • 04:10their ability to move and
  • 04:11to deliver shaped beams. So
  • 04:14most of the treatments were
  • 04:15from the front or the
  • 04:16back of the patient in
  • 04:17a simple
  • 04:18way.
  • 04:20And so we were guided
  • 04:21by what we kind of
  • 04:22refer to as two dimensional
  • 04:24imaging, which is those plain
  • 04:25film x rays.
  • 04:27But, one of
  • 04:28the major advances
  • 04:30in field has
  • 04:32been the use of advanced
  • 04:33imaging like CT scans, MRI
  • 04:35scans, or now even PET
  • 04:37scanning
  • 04:38to create three-dimensional images
  • 04:40of the tumor target.
  • 04:41And that's coupled with
  • 04:43many technological
  • 04:45advances in the linear accelerators
  • 04:47that allow
  • 04:48the delivery of very complex,
  • 04:51beam arrangements that really shape
  • 04:53the dose distribution in a
  • 04:55three-dimensional manner.
  • 04:57And my sense is that
  • 04:58by using those three-dimensional images
  • 05:00like CT scans and with
  • 05:02the changes in some of
  • 05:04your,
  • 05:05equipment that delivers radiation,
  • 05:08two things have happened.
  • 05:09The treatment is far more
  • 05:11effective,
  • 05:12and at the same time,
  • 05:13you can spare patients a
  • 05:15lot of the side effects
  • 05:16that used to be pretty
  • 05:17commonplace.
  • 05:19That's right. Because now we
  • 05:20can shape the dose distribution
  • 05:22a lot more conformally
  • 05:24to the tumor itself
  • 05:26and substantially reduce the dose
  • 05:27to surrounding tissues.
  • 05:30That's allowed us to deliver
  • 05:32the treatments
  • 05:33much more safely with less
  • 05:35side effects.
  • 05:37And in some cases, we
  • 05:38can give a higher dose
  • 05:40each day and reduce
  • 05:42the number of
  • 05:43days of treatment and that's
  • 05:45also a
  • 05:46benefit to patients.
  • 05:48Before we get into some
  • 05:49additional advances,
  • 05:51maybe you could just comment
  • 05:53on some of the myths
  • 05:55that people still carry around
  • 05:57about radiation.
  • 05:59You know, in
  • 06:01not such a different way
  • 06:02than with chemotherapy,
  • 06:03there are a lot of
  • 06:04patients who come see us
  • 06:06and have preconceived notions about
  • 06:09what these treatments are like
  • 06:10and will come in saying,
  • 06:11well, I'm never doing that
  • 06:13because
  • 06:14you know, my great aunt received
  • 06:16that and had some terrible
  • 06:18problems.
  • 06:20What are the specific
  • 06:22misunderstandings
  • 06:23about radiation?
  • 06:25Well, I think that
  • 06:27one is,
  • 06:28what we're alluding to before
  • 06:30is, you know,
  • 06:31historically, some people may remember
  • 06:33that
  • 06:34people treated with sort of
  • 06:36the older fashioned ways of
  • 06:37giving radiation developed
  • 06:39skin burns
  • 06:41that
  • 06:43were very challenging to treat
  • 06:45and to heal. But
  • 06:47the advances that we just
  • 06:48talked about in
  • 06:50delivery of radiation more deeply
  • 06:53into the body and sparing
  • 06:54the skin with shape beams,
  • 06:57has allowed us to substantially
  • 06:59avoid
  • 07:01the skin damage
  • 07:02and also
  • 07:03side effects to other
  • 07:05tissues.
  • 07:08And I'm not saying that doesn't sometimes
  • 07:10happen. There
  • 07:12can be some
  • 07:13side effects to the skin,
  • 07:14but it's much much
  • 07:16less than it used to be for
  • 07:18the skin and for
  • 07:19that matter, other organs too.
  • 07:23There is some
  • 07:25effect of radiation as it
  • 07:27passes through healthy tissue, and
  • 07:29sometimes that can lead to
  • 07:30some fatigue and temporary loss
  • 07:32of energy.
  • 07:34Sometimes, if patients are treated
  • 07:36in the area of the
  • 07:37head and neck, they may
  • 07:38develop dry mouth,
  • 07:41or if they're treated in
  • 07:42the GI tract, they may
  • 07:43have some symptoms
  • 07:45associated with that. But, usually
  • 07:47these symptoms fade over time.
  • 07:49What are some of the
  • 07:50most common uses of radiation?
  • 07:52About sixty percent of all
  • 07:53cancer patients
  • 07:55are treated with radiation and
  • 07:58many different types of tumors
  • 07:59are treated.
  • 08:04One very common treatment is for
  • 08:05cancers of the head and
  • 08:06neck where radiation is considered
  • 08:09a curative treatment often in
  • 08:11combination with chemotherapy.
  • 08:13We do a lot of
  • 08:14radiation treatments for breast cancer,
  • 08:16prostate cancer,
  • 08:18brain tumors,
  • 08:20and, tumors of the GI
  • 08:22tract. I mentioned
  • 08:25gynecologic
  • 08:25malignancies
  • 08:26where radiation is very effective
  • 08:30and routinely achieves
  • 08:32curative effect in many of
  • 08:33those scenarios.
  • 08:35And in some cases, these are
  • 08:37a substitute for
  • 08:39surgery, and in some cases,
  • 08:41it's done in conjunction with
  • 08:43surgery.
  • 08:44Radiation
  • 08:46is particularly effective for localized
  • 08:48disease
  • 08:49and can be an alternative
  • 08:51to surgery in some cases,
  • 08:53either because the individual is
  • 08:55not medically able to undergo an
  • 08:59operation,
  • 09:00or because the
  • 09:03morbidity or side effects
  • 09:05of getting radiation may actually be
  • 09:08more favorable than a surgical
  • 09:10intervention.
  • 09:11Not so many years ago
  • 09:12when someone would have cancer
  • 09:14that unfortunately would spread to
  • 09:16their brain,
  • 09:18they very commonly would
  • 09:20get radiation
  • 09:22to the entire brain, to
  • 09:24the whole head essentially.
  • 09:26And increasingly
  • 09:28over the years, it seems
  • 09:30that that's not the case,
  • 09:31and treatments that are
  • 09:33referred to as either
  • 09:34stereotactic
  • 09:36radiosurgery
  • 09:37or gamma knife
  • 09:39have been used and have
  • 09:41been very effective.
  • 09:42Can you tell us a
  • 09:43little bit about those treatments?
  • 09:45Yes, you're absolutely
  • 09:47right that
  • 09:48years ago for
  • 09:50metastases in the brain,
  • 09:53treatment would be given to
  • 09:54what we call the whole
  • 09:55brain, which is basically the
  • 09:56upper
  • 09:57part of the head through
  • 09:59and through. But the advances
  • 10:01that I was alluding to
  • 10:02in terms
  • 10:04of the technology, the treatment
  • 10:05machines, and also specialized devices
  • 10:07like the gamma knife,
  • 10:09allows very focused treatment of
  • 10:12individual metastatic lesions,
  • 10:15with really exquisite precision that
  • 10:17allow
  • 10:18a good deal of sparing
  • 10:20of the surrounding healthy brain.
  • 10:23So now it's pretty much
  • 10:24standard of care to
  • 10:26treat
  • 10:27the metastatic lesions fairly aggressively,
  • 10:30but with highly focused treatment.
  • 10:32And the Gamma Knife actually
  • 10:33is one of the best
  • 10:34devices to do that for
  • 10:35brain lesions because of its
  • 10:37high precision.
  • 10:39I mean, this has really
  • 10:41transformed
  • 10:42in many ways the treatment
  • 10:44of cancer that has spread
  • 10:45to the brain
  • 10:46and has allowed people to
  • 10:49live longer and at the
  • 10:50same time live much better.
  • 10:54And it's become especially important as systemic
  • 10:56therapies have improved.
  • 10:59So now we are taking
  • 11:02a more aggressive
  • 11:03approach to trying to
  • 11:06treat lesions in the brain
  • 11:08when the systemic disease can
  • 11:10be controlled by other approaches.
  • 11:12It seems that there are
  • 11:14even newer approaches, and you
  • 11:17have a new machine
  • 11:18that gives
  • 11:20guided radiation.
  • 11:21And maybe you can tell
  • 11:23us a little bit about
  • 11:24that, and what
  • 11:26kind of guidance is used?
  • 11:29This is along the lines of what
  • 11:31we call image guided therapy,
  • 11:33in which the linear
  • 11:34accelerators have an onboard imaging
  • 11:36device to help
  • 11:39us evaluate
  • 11:41and modify the treatment
  • 11:43at the time
  • 11:44the patient
  • 11:46is in the machine and
  • 11:48in some cases almost in
  • 11:49real time.
  • 11:51This approach started with CT
  • 11:53scan and MR scan,
  • 11:56included in Lenox, but this
  • 11:58new biologically guided therapy incorporates
  • 12:01a PET scanner or PET
  • 12:02imager in the device. NOTE Confidence: 0.9444651
  • 12:04A PET scanner image
  • 12:07positron emissions from radioactive tracers
  • 12:10that
  • 12:11accumulate in the tumor when
  • 12:13certain
  • 12:14compounds are given to the
  • 12:15patient ahead of time. And
  • 12:17that allows us to account
  • 12:19for the localization of the
  • 12:21tumor,
  • 12:22and also its motion within
  • 12:24the patient, and in some
  • 12:26cases depending on the tracer
  • 12:28we use on its biological
  • 12:29properties.
  • 12:30And then we can modify
  • 12:33the treatment, beamlets,
  • 12:35in real time based on
  • 12:36the positron emission pattern.
  • 12:39How much experience have
  • 12:41you had with this so far?
  • 12:42We've had it going
  • 12:44for about a year, and
  • 12:46actually, I think we have
  • 12:48one of the largest experiences
  • 12:49in the country with this.
  • 12:50So we're getting more familiar
  • 12:52with how to best
  • 12:54incorporate this technology into
  • 12:57our treatment of patients.
  • 12:59So it's really
  • 13:01taking the treatment even
  • 13:03a step further than you
  • 13:05would with just a CT
  • 13:06scan alone
  • 13:08because with
  • 13:09the PET part of that
  • 13:10imaging, you can tell much
  • 13:12more about what's going on
  • 13:13in the tumor.
  • 13:14It has a new dimension.
  • 13:15Right now, it's primarily
  • 13:17valuable for accounting for
  • 13:19motion, especially lesions in the
  • 13:21lung where you have breathing,
  • 13:24the breathing cycle that
  • 13:25causes motion.
  • 13:27But we think that down
  • 13:29the road, we will have
  • 13:30many other applications of the
  • 13:31technology.
  • 13:33Well, this is great. We're
  • 13:34gonna take a break for
  • 13:35just a minute. And when
  • 13:37we come back, we're gonna
  • 13:38talk a little more about
  • 13:40how radiation works, and then
  • 13:41we're gonna get into some
  • 13:43of the research you've done
  • 13:44related to that.
  • 13:46Support for Yale Cancer Answers
  • 13:48comes from Smilow Cancer Hospital,
  • 13:50where all patients have access
  • 13:52to cutting edge clinical trials
  • 13:53at several convenient locations throughout
  • 13:55the region.
  • 13:56To learn more, visit smilowcancer
  • 13:58hospital dot org.
  • 14:02The American Cancer Society estimates
  • 14:04that nearly one hundred and
  • 14:05fifty thousand people in the
  • 14:07U. S. will be diagnosed
  • 14:08with colorectal cancer this year
  • 14:10alone.
  • 14:11When detected early, colorectal cancer
  • 14:13is easily treated and highly
  • 14:15curable,
  • 14:16and men and women over
  • 14:17the age of forty five
  • 14:18should have regular colonoscopies
  • 14:20to screen for the disease.
  • 14:22Patients with colorectal cancer have
  • 14:24more hope than ever before,
  • 14:25thanks to increased access to
  • 14:27advanced therapies and specialized care.
  • 14:30Clinical trials are currently underway
  • 14:32at federally designated comprehensive cancer
  • 14:34centers, such as Yale Cancer
  • 14:36Center and Smilow Cancer
  • 14:38Hospital,
  • 14:39to test innovative new treatments
  • 14:40for colorectal cancer.
  • 14:42Tumor gene analysis has helped
  • 14:44improve management of colorectal cancer
  • 14:47by identifying the patients most
  • 14:49likely to benefit from chemotherapy
  • 14:51and newer targeted agents resulting
  • 14:54in more patient specific treatment.
  • 14:56More information is available at
  • 14:58yale cancer center dot org.
  • 15:00You're listening to Connecticut Public
  • 15:02Radio.
  • 15:03Good evening again. This is
  • 15:04Eric Winer with Yale Cancer
  • 15:06Answers, and I'm here tonight
  • 15:09with my guest,
  • 15:11doctor Peter Glazer,
  • 15:13who is a professor of
  • 15:16therapeutic radiology and a professor
  • 15:18of genetics here at Yale
  • 15:19School of Medicine and chair
  • 15:22of therapeutic radiology.
  • 15:24Can you tell us a
  • 15:25little bit
  • 15:26about
  • 15:27how it is that radiation
  • 15:29on a cellular
  • 15:31level
  • 15:32kills cancer cells? What does
  • 15:34it do that makes
  • 15:36them die?
  • 15:38The radiation
  • 15:39that we use
  • 15:41clinically to treat cancer is
  • 15:42sometimes
  • 15:43classified
  • 15:44as ionizing radiation
  • 15:46to differentiate it from other
  • 15:48forms of
  • 15:51radiation including photons, which is
  • 15:53visible light.
  • 15:56And what that means is
  • 15:57that the radiation, x-ray radiation
  • 15:59goes into cancer cells
  • 16:02and causes ionization of the
  • 16:04molecules
  • 16:05inside the cell, and that
  • 16:07leads to a lot of
  • 16:08chemical reactions that damage the
  • 16:09DNA.
  • 16:11So fundamentally,
  • 16:12radiation causes DNA damage in
  • 16:14cancer cells
  • 16:15and if we can provide
  • 16:17sufficient damage, the cells cannot
  • 16:20fix themselves well enough to
  • 16:22recover
  • 16:23and that leads to a
  • 16:24destruction of the tumor and
  • 16:26tumor regression.
  • 16:28And the DNA is essentially
  • 16:30the brain of the cancer cell?
  • 16:32Yes, DNA
  • 16:33as in all cells, has
  • 16:35the blueprint for how a
  • 16:37cell functions,
  • 16:38and DNA
  • 16:40leads to the production of
  • 16:42downstream molecules like RNA and
  • 16:44proteins. So if you get
  • 16:45the DNA, then you basically
  • 16:47block all cellular functions
  • 16:49and the ability of the
  • 16:50cell to survive.
  • 16:51Now one of the things
  • 16:53that
  • 16:54one hears as a doctor
  • 16:56from patients is the question,
  • 16:58well, doesn't radiation
  • 16:59cause cancer?
  • 17:01And I think people are
  • 17:03often thinking about
  • 17:05the fact that, you know,
  • 17:07repeated,
  • 17:09imaging studies are associated with
  • 17:11a very small increased risk
  • 17:13in cancer in certain circumstances.
  • 17:16Is that a question that
  • 17:17that all of you get
  • 17:19asked a fair amount?
  • 17:20Yes. We sometimes talk about
  • 17:22that with patients. I
  • 17:23I think that it, you
  • 17:25know, it is known that
  • 17:27there is a link between
  • 17:28radiation exposure and
  • 17:31developing malignancies.
  • 17:32I think this is one
  • 17:33of the
  • 17:35key reasons that we've worked
  • 17:36so hard to develop technologies
  • 17:38that focus the radiation
  • 17:40intensively on the tumor and
  • 17:43work to spare the healthy
  • 17:44tissue
  • 17:45as much as we can.
  • 17:48And, you know, we've studied
  • 17:49this a lot in the
  • 17:50field, and the risk of
  • 17:54secondary malignancies
  • 17:55is not zero, but it's
  • 17:56very low, especially for most
  • 17:58adult patients.
  • 17:59We worry a little bit
  • 18:00more about children, which is
  • 18:02one of the reasons that
  • 18:03we spend a lot
  • 18:05of time in developing treatment
  • 18:07approaches for children that are
  • 18:09very highly focused. And
  • 18:11one of the more recent,
  • 18:13two elements along those lines
  • 18:14is the use of proton
  • 18:16beam therapy,
  • 18:17which is
  • 18:19especially valuable for treating
  • 18:21children.
  • 18:22And,
  • 18:23there's gonna be a proton
  • 18:25beam facility
  • 18:26in Connecticut
  • 18:27in the not distant future
  • 18:29that we've been involved with.
  • 18:31Protons
  • 18:34are a type of ionizing
  • 18:35radiation, but instead of x
  • 18:37rays, they use
  • 18:38protons, which are a subatomic
  • 18:40particle,
  • 18:42which a machine
  • 18:44called a cyclotron will accelerate.
  • 18:46And the protons
  • 18:47also enter into the tissue,
  • 18:49but they have a special
  • 18:51property because
  • 18:52they're a particle with mass
  • 18:54that they enter tissue and
  • 18:55they stop suddenly to deposit
  • 18:57their dose.
  • 18:59And that lets us tailor the
  • 19:03delivery of the ionizing radiation
  • 19:05even better.
  • 19:07And,
  • 19:08we think that it has
  • 19:09some advantages.
  • 19:11But developing proton beam facilities
  • 19:13is not a simple endeavor.
  • 19:15It's much more expensive and
  • 19:16involved than
  • 19:18installing a regular LINAC.
  • 19:20And so there are not
  • 19:22many in the country,
  • 19:24and there is
  • 19:25not one in Connecticut right
  • 19:26now, but Yale New Haven
  • 19:28Health System and Hartford HealthCare
  • 19:30have partnered,
  • 19:32and we recently did the
  • 19:33groundbreaking to
  • 19:36advance a new proton beam
  • 19:37facility,
  • 19:39in the center of the
  • 19:40state that'll be
  • 19:42a resource for all of
  • 19:43the people in the region.
  • 19:44And the price tag for
  • 19:46these kinds of facilities is
  • 19:48in the
  • 19:49tens of millions of dollars.
  • 19:52You know, this one is
  • 19:53somewhere in the range of
  • 19:54seventy million all in with
  • 19:56all the construction and
  • 19:58equipment.
  • 20:01Can you
  • 20:02talk about some of your
  • 20:04research?
  • 20:05And
  • 20:06I know some of the
  • 20:07recent research has
  • 20:09related to the treatment of
  • 20:13what is
  • 20:15often thought of as
  • 20:17inherited breast cancer and other
  • 20:19cancers that
  • 20:20arise in the setting of
  • 20:22of BRCA
  • 20:23mutations.
  • 20:25But I know that your
  • 20:27research career stretches
  • 20:29pretty far back. And
  • 20:31what are some of the
  • 20:32things you've worked on over
  • 20:33the years? And then maybe
  • 20:34we can talk more about
  • 20:36BRCA.
  • 20:37Yes, I've
  • 20:39been interested in how
  • 20:41DNA repair pathways can influence
  • 20:43the development of cancer and
  • 20:45how they can be exploited
  • 20:46for treatment.
  • 20:47And you mentioned
  • 20:49the BRCA1
  • 20:50and BRCA2
  • 20:52genes which are linked
  • 20:56to a large extent to
  • 20:57breast and ovarian cancers.
  • 21:00And defects in those genes
  • 21:01lead to a deficiency in
  • 21:04a pathway of DNA repair
  • 21:06called homologous recombination.
  • 21:08We recently discovered that some
  • 21:10other genes that are seen
  • 21:12mutated in cancers
  • 21:14that are linked to abnormal
  • 21:16metabolism
  • 21:18also cause a defect in
  • 21:19the same DNA repair pathway
  • 21:22and we found unexpectedly
  • 21:24that they can be exploited
  • 21:26with
  • 21:27molecularly
  • 21:28targeted agents that
  • 21:31exploit related
  • 21:32DNA repair pathways.
  • 21:35And similar to the situation
  • 21:36with BRCA1 and BRCA2,
  • 21:38these genes include
  • 21:41genes with the names IDH1
  • 21:42and two, SDH and FH
  • 21:45and they're linked to
  • 21:47brain tumors, sarcomas, kidney cancers
  • 21:49and others.
  • 21:51Some of the strategy that
  • 21:52we and others have worked
  • 21:54on, you can think of
  • 21:55it like a traffic pattern
  • 21:56since you and I live
  • 21:57in Southern Connecticut.
  • 21:59If there's a big
  • 22:00crash on I-95
  • 22:02and you can't get where
  • 22:03you're going, you might think
  • 22:04of going to the Merritt
  • 22:05Parkway,
  • 22:06but we're using an agent
  • 22:08that blocks the Merritt Parkway,
  • 22:09so then you have nowhere
  • 22:10to go.
  • 22:11And so, we're taking that
  • 22:13kind of approach for these
  • 22:15genetically linked cancers.
  • 22:17And this is by developing
  • 22:19drugs?
  • 22:20Yeah. Drugs that target other
  • 22:22DNA repair pathways. So there's
  • 22:24a well known class of
  • 22:25drugs called PARP inhibitors.
  • 22:27We did not develop them,
  • 22:28but we're trying to find
  • 22:30new uses for them.
  • 22:32Another thing that we did
  • 22:33was, we found that agents
  • 22:35that inhibit
  • 22:37angiogenesis,
  • 22:38which means the development of
  • 22:40new blood vessels,
  • 22:42these can lead to reduced
  • 22:44oxygen in tumors, a situation
  • 22:46known as hypoxia.
  • 22:47And that,
  • 22:49we found, causes decreased DNA
  • 22:51repair,
  • 22:51and we can then exploit
  • 22:53that situation with some of
  • 22:54the agents I just talked
  • 22:56about.
  • 22:57And is there a role
  • 22:58for using radiation
  • 23:00in combination with some of
  • 23:01these therapies?
  • 23:03Yes, for sure.
  • 23:04Some of these DNA repair
  • 23:05inhibitors like PARP inhibitors,
  • 23:08and others that are in
  • 23:09clinical development, there's a number
  • 23:10of targeted agents,
  • 23:12that we and others are
  • 23:14working on to
  • 23:15inhibit repair pathways that are
  • 23:17important
  • 23:19to how the cancer cell
  • 23:20tries to fix
  • 23:22the type of DNA damage
  • 23:23the radiation causes.
  • 23:25And if I can just
  • 23:26explore one other combination that's
  • 23:29been talked about recently. So
  • 23:31immunotherapy,
  • 23:32of course, has become,
  • 23:35the treatment of the past
  • 23:37decade. It's used in
  • 23:40well over a dozen different
  • 23:42tumor types and can be
  • 23:44highly effective.
  • 23:45But there's some suggestion that
  • 23:47radiation could also augment the
  • 23:50effect of immunotherapy.
  • 23:52Yes. I think there's
  • 23:54a lot of intense study,
  • 23:56both basic science and in
  • 23:57the clinic, on how to
  • 23:58best combine radiation and immunotherapy.
  • 24:02Radiation can
  • 24:04elicit an inflamed response in
  • 24:06tumors that
  • 24:09synergizes
  • 24:10with the type of immune
  • 24:11response that
  • 24:12these immune checkpoint inhibitors will
  • 24:14provoke.
  • 24:16It is also thought
  • 24:17that radiation can cause the
  • 24:19release of tumor antigens and
  • 24:22sort of create an in
  • 24:23situ tumor vaccine, if you
  • 24:25will.
  • 24:27So, you know, in general,
  • 24:29it's thought that
  • 24:30radiation can enhance the effectiveness
  • 24:33of tumor
  • 24:34immune therapy and vice versa,
  • 24:36that immune therapy or immune
  • 24:38response will enhance the effect
  • 24:39of radiation.
  • 24:42Have you seen a
  • 24:43change in the
  • 24:45type of
  • 24:47medical student who goes into
  • 24:50radiation oncology today versus
  • 24:52twenty or thirty years ago?
  • 24:54It would seem to me
  • 24:55that a lot of these
  • 24:56people must be people who
  • 24:57are
  • 24:59interested in physics and interested
  • 25:01in science and
  • 25:04perhaps interested
  • 25:05in pursuing careers in research.
  • 25:08Yes. I think it's always
  • 25:09been a research friendly
  • 25:12specialty because there's a lot
  • 25:13of basic science, and cellular
  • 25:16biology to explore as well
  • 25:17as the physics and the
  • 25:18more technological
  • 25:21aspects.
  • 25:21I think that, you know,
  • 25:23years ago, it
  • 25:25was felt, well, maybe people
  • 25:26who had a little bit
  • 25:27more proclivity for physics might
  • 25:29go into the field. But
  • 25:30actually, I think the field
  • 25:31now
  • 25:33attracts,
  • 25:34people that like
  • 25:36advanced technology that we can
  • 25:38bring to bear, the image
  • 25:39guidance, the
  • 25:41treatment planning that, you know,
  • 25:42is very computerized and visual,
  • 25:47so I think it's expanded
  • 25:49the reach of people that
  • 25:50are
  • 25:51interested in the field. And
  • 25:52the other thing is I
  • 25:53think people have come to
  • 25:54know that
  • 25:55we're a very patient oriented
  • 25:57specialty,
  • 25:59just like your specialty medical
  • 26:01oncology. We're very patient facing,
  • 26:03and, we have longitudinal
  • 26:05relationships with our patients, and
  • 26:07I think that that attracts
  • 26:09the medical students as well.
  • 26:11Longitude and relationships with your
  • 26:12patients
  • 26:14and, of course, close relationships
  • 26:16with your colleagues since
  • 26:18in the care of patients
  • 26:19with cancer we
  • 26:22all work together since it
  • 26:24takes
  • 26:25far more than any one
  • 26:27discipline.
  • 26:28And as we
  • 26:30wrap up,
  • 26:32can you
  • 26:33speculate about where radiation
  • 26:36oncology
  • 26:37is going over the course
  • 26:38of the next
  • 26:40ten or twenty years?
  • 26:43What should we be looking for?
  • 26:44Well, I think that we're
  • 26:45gonna see a greater
  • 26:47ability to
  • 26:48achieve real time adjustments in
  • 26:50the treatment,
  • 26:51using some of these onboard
  • 26:52imaging technologies. And as the
  • 26:55software
  • 26:56and hardware improves
  • 26:58and we can incorporate things
  • 27:00like artificial intelligence to identify
  • 27:03the tumor targets, track how
  • 27:04they move and adjust radiation
  • 27:07treatments.
  • 27:08That's going to allow even
  • 27:09more precise
  • 27:10and tailored
  • 27:12radiation therapy for patients.
  • 27:14I think also we're going
  • 27:15to see more individualized
  • 27:16patient treatments based on clinical
  • 27:18and genetic characteristics
  • 27:20And, like we were alluding
  • 27:22to before,
  • 27:23I see the next five
  • 27:24or ten years,
  • 27:26that we will be able
  • 27:27to deploy new targeted biological
  • 27:29agents that sensitize tumors to
  • 27:31radiation
  • 27:32without
  • 27:34sensitizing healthy tissues. And,
  • 27:36for example, we're
  • 27:37working in the lab to
  • 27:38develop a class of peptide
  • 27:40drug conjugates that does just
  • 27:42that.
  • 27:43And the preclinical models look
  • 27:45encouraging, so hopefully that will
  • 27:47eventually make its way to
  • 27:48the clinic.
  • 27:50And not to set up a
  • 27:51competition with surgery, but do
  • 27:53you think these changes
  • 27:54will lead to fewer surgical
  • 27:56procedures
  • 27:57and more radiation?
  • 27:59Well, I think it
  • 28:00may change the balance for
  • 28:02certain tumors. I think I've
  • 28:04seen that the pendulum has
  • 28:06swung back and forth,
  • 28:08for different, types of tumors
  • 28:10where,
  • 28:12you know, radiation approaches,
  • 28:14are more favored and then
  • 28:16surgical. It really
  • 28:17depends. I mean, the surgeons
  • 28:19have been very good to
  • 28:20advance their technology to robotic
  • 28:22surgeries and minimally invasive surgeries.
  • 28:24So I think it's all
  • 28:25to the good for the
  • 28:26patients, and we'll just have
  • 28:28more choices for figuring out
  • 28:30the best treatments.
  • 28:31Doctor Peter Glazer is the
  • 28:33Robert E Hunter Professor of
  • 28:34Therapeutic Radiology and Professor of
  • 28:36Genetics and Chair of the
  • 28:38Department of Therapeutic Radiology at
  • 28:40the Yale School of Medicine.
  • 28:42If you have questions, the
  • 28:43address is canceranswers
  • 28:44at yale dot edu, and
  • 28:46past editions of the program
  • 28:47are available in audio and
  • 28:49written form at yalecancercenter
  • 28:51dot org. We hope you'll
  • 28:52join us next time to
  • 28:53learn more about the fight
  • 28:54against cancer.
  • 28:55Funding for Yale Cancer Answers
  • 28:57is provided by Smilow Cancer
  • 28:59Hospital.