Episode 131: Christopher Logothetis discusses advances in prostate cancer therapies
STEM-Talk
The Spiral of Cancer Progression
Ajuss: Can you talk about this spiral of cancer progression? And ajuss, it was a really nice paper. Thank you. So the way we thought about it, the development of of metastases and the sort of new appreciation for the micro environment in contributing to this led into these concepts of this vicious cycle. There would be an a vector of o change, remodelling the micro environment by the cancer to the specific micro environment,. In turn, a response that would result in this self perpetuating cycle.
Our guest today is Dr. Christopher Logothetis, one of the nation’s foremost experts on prostate cancer. Chris has spent nearly five decades at MD Anderson in Houston developing therapies for prostate cancer as well as conducting research into the underlying biology of the disease.
Aside from skin cancers, prostate cancer is the most common cancer among men, claiming a man’s life every 15 minutes in the United States, according to the Prostrate Cancer Foundation. Since the 1970s when Chris joined the staff at MD Andersen, which is the nation’s top-ranked hospital for cancer care, he has been dedicated to the treatment, research, and prevention of genitourinary cancers such bladder, kidney, testes and penis cancer. For the past 25 years, he has focused primarily on prostate cancer and the development of effective chemotherapy treatments.
Today, Chris is the director of MD Anderson’s Genitourinary Cancer Center and the director of the Prostate Cancer Research Program.
Show notes:
[00:03:23] Dawn opens the interview mentioning that Chris went to medical school in Greece and asks if he grew up there as well.
[00:03:43] Ken asks Chris when he first became interested in science.
[00:04:09] Dawn asks if there were a particular teacher or class that prompted Chris’ decision to pursue medicine.
[00:04:39] Dawn asks what led Chris to attend the University of Athens School of Medicine.
[00:05:10] Dawn mentions that in the ‘60s and ‘70s, talking about cancer was almost taboo and asks Chris to talk about the stigma that surrounded cancer for quite some time.
[00:05:57] Ken asks if Chris knew he wanted to specialize in cancers when he first started medical school in Athens or if that interest developed later.
[00:07:06] Dawn mentions that Chris graduated from medical school in 1974 and then took off for Chicago where he had an internship at Cook County Hospital. Dawn asks about the experience, and if it were a culture shock to go from Athens, Greece to Chicago in the 1970s.
[00:08:54] Dawn asks what took Chris to Texas and MD Anderson after his time in Chicago.
[00:09:36] Dawn mentions that after Chris finished his fellowship, he joined the faculty at MD Anderson, and is now coming upon his 50th anniversary there.
[00:09:51] Chris explains his view that we need to better understand the drivers of cancer and goes on to talk about what we currently know about these drivers.
[00:12:06] Ken asks about the significance of the Human Genome Project on cancer research.
[00:13:49] Dawn mentions that along with new technologies, there evolved a strategy of what is called co-clinical investigation where researchers study the mouse, but in parallel look at the difference and similarities with humans. She asks him about how that integrated data required a new language to bring it all together, which is now known as Prometheus. Dawn asks Chris to talk about Prometheus and how this has led to an accelerated understanding of cancer biology.
[00:20:47] Dawn mentions that Chris has studied a range of genitourinary cancers throughout his career, such as germ cell tumors, bladder, and renal cancers, but that his interest in prostate cancer is a more recent development. Dawn asks what led to this specific interest.
[00:23:12] Dawn explains that metastatic cancer was first cured in 1956 when methotrexate was used to treat a rare tumor called choriocarcinoma. She goes on to say that since then, chemotherapy drugs have been used to treat mixed germ-cell tumors and has led to dramatically improved survivorship among patients with metastatic germ-cell tumors. She also mentions that in 1982 Chris published a paper in the journal Cancer titled, “The growing teratoma syndrome,” at which time, tumor growth following chemotherapy for mixed germ-cell tumors had been considered a reliable indicator of a persistent active carcinoma, with the rule being that if the cancer didn’t respond to treatment that operations were futile. Dawn explains that in Chris’ 1982 paper, he demonstrated that you could alter a tumor with chemotherapy in such a way that surgery could now cure it where previously could not. Chris expounds on this paper and its significance.
[00:27:21] Ken mentions that Chris had another paper where he described the spiral diagram of cancer progression, where the cancer sends a message to the host, which sends a message back in a cycle over time. Ken goes on to say that Chris’ conclusion was that this interaction between the cancer and the host eventually evolves into the patient’s body and becomes, in a sense, complicit in the cancer’s growth. Chris goes on to explain the spiral of cancer progression.
[00:31:19] Dawn points out that in the spring of 2021, Chris published a paper in Clinical Cancer Researched titled “Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles From the Metastatic Prostate Cancer Bone Microenvironment.”Dawn goes on to explain that Radium-223 is a radiopharmaceutical used to treat metastatic cancers in bone. Bone-targeting radiotherapy with Radium-223 prolongs the survival of patients with metastatic prostate cancer. Treatment, however, is often followed by a detrimental relapse and progression. Dawn explains that despite this, Chris detailed in his aforementioned paper a treatment strategy that could potentially increase the effectiveness of Radium-223.
[00:34:24] Ken mentions that prostate-specific antigen test, or PSA, has become controversial for its utility as a screen, and asks Chris for his thoughts on the matter.
[00:36:09] Ken asks if a change in PSA levels in a patient over time is more of an elucidating marker than a single high value at one point in time.
[00:38:20] Dawn mentions that Chris wrote in a paper that appeared in the Journal of Cell Science & Therapy. “When we aspire to cure cancer, we need to search no further than a curable cancer such as germ cell tumor of the testis, also known as TGCT.” Dawn asks Chris to expound on this paper and how TGCT provides us invaluable lessons about curing other intractable solid tumors.
[00:41:18] Ken mentions that Chris and his colleagues at MD Anderson and the School of Medicine at the University of Thessaly in Greece wrote an opinion piece that ran in European Urology titled “Prostrate Cancer: Quo Vadis?” The article stressed that utility measures are urgently needed for the clinical application of new diagnostics to reduce excessive intervention. Ken asks Chris to provide more background on this piece and describe the type of diagnostics he and his colleagues recommend in it.
[00:44:27] Dawn explains that while there has been some very promising research into the development of a stress response therapy, metastatic prostate cancer remains an incurable disease, and no effective therapies have yet come out of the research. She goes on to say that Chris addressed this issue in a 2018 article in Science Translational Medicine titled “ER stress in prostate cancer: A therapeutically exploitable vulnerability?” The article was in response to a paper that also appeared in Science Translational Medicine titled “Development of a stress response therapy targeting aggressive prostate cancer.” Dawn asks why Chris wrote this response, and since the publishing of these papers, if there has been much progress in developing effective therapies that target these aggressive prostate cancers.
[00:49:12] Dawn mentions that prostate cancer is a highly heritable disease with disparities in incidence rate across ancestry populations, with the Prostate Cancer Foundation saying that this is one of the largest health disparities in all of medicine. Dawn asks Chris what his thoughts are on this in light of his investigations into the issue.
[00:51:29] Ken explains that there is a precision prostate cancer screening in development called the “Smith Test,” which is something that could help address the disparities in incidence rates across ancestry populations. He goes on to say that the test is described as a simple blood test, similar to a cholesterol test, that would be able to indicate the lifetime risk of prostate cancer of any man. Chris gives his thoughts on this effort.
[00:55:35] Since the death rate from prostate cancer dropped more than 50 percent since the establishment of the Prostrate Cancer Foundation in 1993, Dawn asks Chris about research on the horizon that gives Chris the most hope.
[00:58:27] Dawn mentions Chris’ evening lecture at IHMC titled “Addressing Paradoxes in Health Care,” and asks Chris to give a short summary of his talk.
[01:02:25] Dawn asks if Chris is currently considering retirement anytime soon.
[01:04:16] Ken asks about Chris’ passion for sailing.
[01:06:40] Dawn closes the interview asking if it is true that Chris is such an avid sailor that he has a sailboat in Greece as well as Texas, and that he does some of his best work on sailboats.
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