Friday, July 19, 2024
Mitochondrial Health

#62 – Keith Flaherty, M.D.: Deep dive into most cancers—Historical past of oncology, novel approaches to therapy, and the thrilling and hopeful future

On this episode, Keith Flaherty, director of medical analysis and focused most cancers remedy at Massachusetts Common Hospital, shares his huge wealth of data in most cancers beginning with the historical past of therapy from chemotherapy to radiation to surgical remedy and the place these methodologies appeared to have leveled off. He additionally walks us via the timeline of developments (and lack there of) from when the Conflict on Most cancers was declared within the 1970s, via the sequencing of your complete human genome, and all the best way to at the moment. Keith dives into the subject of immunotherapy, in all probability probably the most thrilling latest improvement in most cancers remedy, and likewise supplies us a rundown of his notion of a distinct method to most cancers that assaults all of the important pillars of most cancers progress and survival. Lastly, we speak just a little bit about liquid biopsies, we talk about the roles of CRISPR and different probably over-hyped therapies with respect to most cancers. We additionally contact on stem cell remedy a bit, in addition to another widespread cancer-related questions such because the position of vitamin D and solar publicity in melanoma, and way more. 


We talk about:

  • Rising up round drugs, and discovering a profession that you just love [7:30];
  • Medication as a profession, limitations of the med faculty instructing method, and the dynamic and accelerating discipline of medication and expertise [16:30];
  • Explaining chemotherapy, radiation, and the way a most cancers develops [23:45];
  • Surgical oncology, treatment fee of strong tumors, and survival fee after tumor elimination  [33:15];
  • 25 years after the Conflict on Most cancers is asserted, gene sequencing, and why Keith’s was fascinated by the HIV case examine [37:15];
  • Most cancers immunotherapy: Historical past, the way it works, and why some cancers reply and others don’t [46:00];
  • MHC complexes, and most cancers cloaking mechanisms [56:00];
  • Comparative biology of most cancers: Why some most cancers can evade immune detection higher than others [1:03:00];
  • What we discovered from the Most cancers Genome Atlas Venture [1:07:00];
  • Defining focused remedy, HER2 breast most cancers, persistent leukemia, and the translocation of chromosomes [1:12:00];
  • Tumor protein P53, probably the most well-known tumor suppressor gene and its ubiquity in most cancers [1:17:45];
  • Activated oncogenes, the RAS pathway, PI3 kinase, RAF gene, and Keith’s “aha second” [1:24:15];
  • Recommendation for beginning your profession as a scientist/clinician [1:37:00];
  • Fusion-driven cancers, focused remedy, and the Bcr-Abl/persistent myelogenous leukemia case examine [1:39:45];
  • Focused remedy for fusion-driven strong tumors, adjuvant systemic remedy, and the HER2 breast most cancers instance [1:53:00];
  • Advancing melanoma therapy, survival, and treatment charges with BRAF-MEK combo remedy [1:59:15];
  • The basic pillars of most cancers progress and survival, and the toolkit we have to assault most cancers from all angles [2:02:40];
  • Peter’s medical framework for desirous about most cancers and the way Keith would possibly enhance it, and the way the biotech atmosphere is hampering our skill to place collectively novel most cancers remedies [2:05:00];
  • How helpful is CRISPR when it comes to tumor suppressing? [2:16:15];
  • Liquid biopsies as a therapeutic monitoring device [2:18:00];
  • Stem cell remedy: The efficacy and potential dangers [2:25:15];
  • Getting old and most cancers: Is most cancers inevitable? [2:28:45];
  • Vitamin D dietary supplements, solar publicity, melanoma, and train [2:32:30];
  • How and why Keith has straddled the road between science/analysis and business/drug corporations, and the significance of getting extra voices of practitioners on the desk [2:42:00]; and
  • Extra.


Rising up round drugs, and discovering a profession that you just love [7:30]

The place are you from?

  • Born and raised in Baltimore
  • Broke away to boarding faculty in Massachusetts for 4 years
  • Connecticut for faculty, 4 years, 
  • then again to Baltimore, 4 years of medical faculty. 
  • Boston for the primary time, three years of residency and
  •  then, Philadelphia for 9 years, which was each medical oncology fellowship and my first college stint. 
  • And now, ten years in the past, moved again as much as Boston to Mass Common. 

Rising up round drugs

  • Father and mom have been physicians
  • My father was an educational heart specialist for 25 years
  • Mother was an educational psychiatrist, truly, actually nonetheless is on the age of now

When do you know you wished to enter drugs?

  • Knew he wished to “assist” folks is a way or one other
  • Didn’t need to go into the “enterprise” world
  • He additionally noticed that each his mother and father have been very captivated with what they have been doing
  • Ultimately, drugs simply appeared to face out among the many profession choices

The high quality line for fogeys: “being residence” vs. “setting an instance” when it comes to seeing them engaged on one thing with ardour and self-discipline 

  • There’s one thing to be stated when that youngster sees their mother or dad feeling extremely captivated with what they’re doing
  • For instance, Keith’s spouse (Mira Kautzky)

    • She’s an internist at Mass Common
    • They watch her pour herself into the oblique care of sufferers via the digital medical report and consistently replicate that she’s the toughest working particular person they know. 
    • That sort of willingness to present, give, give outdoors of 1’s private time, household time, is said to this very nebulous notion of what it’s that certified as a satisfying profession

Keith feels luck to do what he does for a residing

  • Keith appears like most individuals dislike their job they usually’re simply holding their breath making an attempt to get to the weekend
  • He says he’s a part of that small group of people that love what they do
  • That stated, his work/life steadiness has been “off the rails” when it comes to working lengthy hours and being over dedicated and making an attempt to juggle method too many issues
  • Nevertheless, he would additionally say that “it was precisely the optimum quantity of chaos that one wants to essentially really feel such as you’re pushing on all fronts concurrently” 
  • How do you each discover the outlet and outline the scope of a profession that permits you to do this? ⇒ “What a problem!
  • Keith believes the altering instances will possible create a fair greater problem for future generations

Medication as a profession, limitations of the med faculty instructing method, and the dynamic and accelerating discipline of medication and expertise [16:30]

Peter says, the trail to “educational success”, non-academic medical success, it’s nonetheless comparatively unperturbed in comparison with so many different paths outdoors of medication… does Keith agree?

  • “I don’t see it that method” says Keith
  • Keith sees how quickly the expertise and wealth of data is accelerating 
  • Issues like knowledge technology, skill to provide excessive dimensional knowledge, analyze it, attempt to make sense of it, elevate hypotheses, check hypotheses, but the cycle time is altering quite a bit, and the constituents that we now have to work together with are completely totally different
  • The purpose I’m coming to… I see drugs now as this terrifying enviornment through which to attempt to assemble a multi-decade lengthy profession

How do you retain your self related in a 40 yr arc? Keith posits…

  • Right here I’m at 20 years, I really feel like I’m an absolute dinosaur
  • Keith wonders how the brand new technology of physicians and scientists will sustain with this quickly accelerating progress

Peter’s take: 

  • Based mostly on the best way you’re describing it, Keith, I might say medical doctors popping out of coaching are hosed, as a result of … I believe medical faculty could be one of the anti-intellectual types of larger training that exists
  • Peter says even in undergraduate, legislation faculty, Ph.D. packages… you might be inspired to suppose creatively, and downside clear up
  • In different phrases, “I’m unsure medical faculty teaches you tips on how to be a thinker or a problem-solver”

*Tip*: don’t take pre-med previous to med faculty (i.e., examine engineering, humanities, or one thing completely unrelated)

Keith’s tackle med faculty and past:

  • Medical faculty teaches data as reality
  • When speaking to folks about most cancers as a profession, he tells them, “look, it’s so easy to seek out the boundary between what’s recognized and never recognized. There’s a lot on the market we don’t know and in any space of making an attempt to grasp physiology, pathophysiology, within the mode of most cancers, you’ll so rapidly get to that frontier.”

After which, how do you use in that frontier? 

  • When you’re there, how do you assist the affected person in entrance of you, the subsequent wave of sufferers which are coming within the not too distant future, after which a full technology out? 
  • Investigation is the one method you’ll be able to pose your self as being useful. And  I didn’t get that in medical faculty, sadly, although I used to be at a improbable atmosphere for studying the archival model of medication.

Explaining chemotherapy, radiation, and the way a most cancers develops [23:45]

Defining chemotherapy

  • It’s truly not arduous to kill a most cancers cell, it’s truly very simple to kill a most cancers cell:

    • Bleach
    • Formaldehyde
    • “Go to House Depot, most issues on the shelf kill most cancers completely.”
  • Drawback is, they kill the whole lot completely 
  • The arbitrage is the next…

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Keith Flaherty, M.D.

Keith Flaherty is director of Developmental Therapeutics on the Massachusetts Common Hospital Most cancers Middle and affiliate professor of medication at Harvard Medical Faculty. He additionally serves as editor in chief of the journal, Clinical Cancer Research. He was beforehand a professor of medication on the College of Pennsylvania. He’s recognized for his analysis on focused therapies for most cancers, and particularly for his work on the melanoma drug vemurafenib. In 2013, Massachusetts Common Hospital partnered with AstraZeneca to associate Flaherty’s analysis into growing a components to establish vulnerabilities of tumors with AstraZeneca’s library of medicine.

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