Lewis C. Cantley

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Lewis C. Cantley
Born (1949-02-20) February 20, 1949 (age 75)
Weill Cornell Medical College
Harvard Medical School
Beth Israel Deaconess Medical Center
Tufts University
Harvard University
Doctoral advisorGordon Hammes
Other academic advisorsGuido Guidotti

Lewis C. Cantley (born February 20, 1949) is an American cell biologist and biochemist who has made significant advances to the understanding of cancer metabolism. Among his most notable contributions are the discovery and study of the enzyme

diabetes mellitus.[1][2] He is currently Meyer Director and Professor of Cancer Biology at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York City. He was formerly a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston
, Massachusetts. In 2016, he was elected Chairman of the Board for the Hope Funds for Cancer Research.

Biography

Cantley grew up in

NewYork–Presbyterian Hospital in 2012.[1][2][3][4] Dr. Cantley was elected the Chairman of the Board of the Hope Funds for Cancer Research in 2016.[5]

Cantley is married to Vicki Sato, herself a prominent figure in the pharmaceutical industry and a professor at Harvard University in both the Business and Medical Schools.

Research

Discovery of PI-3-kinase and PtdIns(3,4)P2[1][2][6]

In a series of studies spanning several years, Cantley and colleagues demonstrated that a kinase activity associated with the middle T oncoprotein is a

PI-3-kinase) is activated by growth factors to produce novel 3'-phosphorylated phosphoinositides, in particularly PtdIns(3,4,5)P3[9] that had previously been identified in physiologically stimulated human neutrophils.[10] In subsequent years Cantley and colleagues identified critical aspects of the regulation of PI-3-kinase by growth factor receptors. Specifically, they discovered that the catalytic subunit p110 dimerizes with the regulatory subunit p85,[11] and that the SH2 domain of p85 specifically recognized phosphotyrosines[12] on growth factor receptors or adaptor proteins via the pY-X-X-M motif.[13][14]

The Cantley lab has also made seminal contributions to understanding signaling downstream of PI-3-kinase. They discovered that the Pleckstrin Homology domain of

LKB1 as a regulator of AMPK that also serves to regulate TORC1.[20][21]

For the discovery of PI-3-Kinase and its role in cancer metabolism, Cantley was one of eleven recipients of the inaugural Breakthrough Prize in Life Sciences, "the world's richest academic prize for medicine and biology. The prize, which carries a $3 million cash award, recognizes excellence in research aimed at curing intractable diseases and human life."[22] The fundamental and far-reaching nature of the discovery of PI-3-kinase, together with Cantley's role in mapping the upstream regulation of PI-3-kinase and the downstream signaling pathways, have led to speculation that Cantley is a likely candidate for the Nobel prize in Medicine or Physiology.[23] The growing evidence for a primary role for PI-3-kinase in cancer[24][25] and its critical role in insulin signaling[26] have served to strengthen the significance of this fundamentally important discovery.

The first drug targeting the PI-3-kinase pathway as a treatment for cancer - Idelalisib (PI3K Delta inhibitor) - was approved by the FDA as a treatment for leukemia and two types of lymphoma in July 2014.[27] Other drugs are currently in clinical development.

Use of Oriented Peptide Libraries to determine phosphopeptide binding specificity and protein kinase substrate specificity

In 1994, the Cantley lab published a novel strategy to determine the sequence specificity of phosphopeptide binding domains (initially SH2 domains).[13] Subsequently, the oriented peptide library approach was extended to identify the substrate specificity of protein kinases toward synthetic peptides.[28] This approach was then extended to characterize the specificity of Ser/Thr kinases and phospho-Ser/Thr binding domains.[29] This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity matrices generated from these experiments served as the basis for creating the website Scansite, allowing the de novo identification of candidate phosphorylation sites in an arbitrary protein.[30][31]

In later research, the oriented peptide library approach has also been used to characterize protease cleavage specificity.[32] Modification of the original oriented peptide approach has allowed for large scale, kinome-wide determination of protein kinase specificity.[33]

Discovery of PtdIns(5)P

In 1997, the Cantley lab discovered that the enzymes that had been referred to as type II PIP-kinases, instead of using PtdIns(4)P as a substrate, in fact required PtdIns(5)P as a substrate to produce PtdIns(4,5)P2.[34] Further research demonstrated that PtdIns(5)P is naturally occurring in all eukaryotes.

It is remarkable that of the seven naturally occurring phosphoinositides, the existence of four of them (PtdIns(5)P, PtdIns(3)P, PtdIns(3,4)P2, and PtdIns(3,4,5)P3) was discovered by Cantley and colleagues.[8][9][34][35]

Role of metabolism in cancer

The role of PI-3-kinase in anabolic signaling by insulin, IGF-1, and other growth factors makes a straightforward link between metabolism and cancer, especially in light of the discovery that the PIK3CA gene encoding PI-3-kinase is an oncogene.[36]

In recent years Cantley and colleagues have made additional links between metabolic regulation and oncogenic transformation with their discovery that the M2 isoform of pyruvate kinase is associated with cancer.[37][38] This discovery provides a molecular basis for understanding the Warburg effect. Cantley is now a major player in the resurgence of the importance of the Warburg effect in the process of oncogenesis.[39]

Role of PI-3-kinase in different cancers

Cantley was part of the Stand Up to Cancer "dream team" that was brought together to investigate ways to target PI-3-kinase as a way to treat women's cancers, and he now leads a national effort targeting triple-negative breast cancer and ovarian cancer with novel drug combinations.[40] Recent research found that high levels of Vitamin C halted the growth of aggressive forms of colorectal tumors.[41] His lab also elucidated the role of Nrf2 in serine production in non-small cell lung cancer, with potential implications for pancreatic and other cancers as well.[42]

Industrial activities

Lewis C. Cantley has been involved in numerous companies. Recent examples include the following:

Awards, honors and media appearances

Cantley has received numerous awards and honors, including:

  • ASBMB Avanti Award for Lipid Research (1998)[48]
  • Elected to the American Academy of Arts and Sciences (1999)[49]
  • Heinrich Wieland Prize for Lipid Research (2000)
  • Elected to the National Academy of Sciences (2001) [1]
  • Caledonian Prize from the Royal Society of Edinburgh (2002)[50]
  • Pezcoller-AACR International Award for Cancer Research (2005)[51]
  • Rolf Luft Award of the Karolinska Institute (2009)[52]
  • Pasrow Prize for Cancer Research (2011)
  • Breakthrough Prize in Life Sciences (2013)
  • Jacobaeus Prize for Diabetes Research, from the Karolinska Institute (2013) [53]
  • Elected to the Institute of Medicine of the National Academies (2014)[54]
  • AACR Princess Takamatsu Memorial Lectureship (2015) [55]
  • Ross Prize in Molecular Medicine (2015) [56]
  • Canada Gairdner International Award (2015) [57]
  • Elected to European life sciences academy EMBO (2015) [58]
  • The Association of American Cancer Institutes Distinguished Scientist Award (2015) [59]
  • Thomson Reuter's "The World's Most Influential Scientific Minds 2015".[60]
  • The Wolf Prize in Medicine (2016) [61]
  • The Hope Funds Award of Excellence in Basic Science (2016)
  • Louisa Gross Horwitz Prize (2019) [62]

He appeared in the 60 Minutes program "Is sugar toxic?".[63]

References

  1. ^
    PMID 14993589
    .
  2. ^
    S2CID 19060385
    .
  3. ^ "Weill Cornell Medical College and NewYork-Presbyterian Hospital Announce New Powerhouse Recruit for Cancer Research and Patient Care". Weill Cornell Medical College. Retrieved 2016-01-05.
  4. ^ Alberta Cancer Foundation International Advisory Board Archived 2009-08-31 at the Wayback Machine
  5. ^ "Front Page". 30 October 2018.
  6. ^ Cantley, LC. "From Kinase to Cancer." The Scientist, December 2007.
  7. S2CID 4337999
    .
  8. ^
    S2CID 4326568
    .
  9. ^
    S2CID 22154860
    .
  10. S2CID 4263472
    .
  11. PMID 2174051
    .
  12. PMID 7683653
    .
  13. ^
    PMID 7680959
    .
  14. PMID 8065326
    .
  15. S2CID 31186873
    .
  16. PMID 9268346
    .
  17. PMID 12150915
    .
  18. PMID 12271141
    .
  19. S2CID 6519150
    .
  20. PMID 14985505
    .
  21. PMID 15261145
    .
  22. ^ "Dr. Lewis Cantley Awarded $3 Million Breakthrough Prize in Life Sciences for Excellence in Cancer Research". Press Release, Weill Cornell Medical College. Feb 21, 2013. Retrieved 1 November 2013.
  23. ^ Palazzo, Alex (October 1, 2008). "Gaze into the crystal ball – Nobel Prize Predictions". Transcription and Translation. ScienceBlogs. Retrieved 1 November 2013.
  24. PMID 20085938
    .
  25. PMID 20006486
    .
  26. PMID 12040186
    .
  27. ^ "Press Announcements - FDA approves Zydelig for three types of blood cancers". www.fda.gov. Archived from the original on 2016-01-03. Retrieved 2016-01-05.
  28. S2CID 7507217
    .
  29. S2CID 14107687
    .
  30. S2CID 22637369
    .
  31. PMID 12824383
    .
  32. S2CID 13510196
    .
  33. S2CID 4671684
    .
  34. ^
    S2CID 4403301
    .
  35. PMID 2555343
    .
  36. S2CID 10147415
    .
  37. S2CID 16111842
    .
  38. S2CID 4346405
    .
  39. PMID 19460998
    .
  40. ^ "Pioneering Personalized Medicine | Sandra and Edward Meyer Cancer Center". meyercancer.weill.cornell.edu. Retrieved 2016-01-05.
  41. ^ "Vitamin C halts growth of aggressive forms of colorectal cancer in preclinical study | Sandra and Edward Meyer Cancer Center". meyercancer.weill.cornell.edu. Retrieved 2016-01-05.
  42. ^ "Cantley team uncovers vulnerability that can be exploited to kill lung cancer cells | Sandra and Edward Meyer Cancer Center". meyercancer.weill.cornell.edu. Retrieved 2016-01-05.
  43. ^ "Eli Lilly, Pfizer, J&J, AbbVie Join $48M Bet On NYC Cancer Drug Startup". Forbes. Retrieved 2016-01-06.
  44. ^ Agios Pharmaceuticals
  45. ^ Volastra Therapeutics
  46. ^ AVEO Pharmaceuticals Archived 2010-07-30 at the Wayback Machine
  47. ^ TransMolecular, Inc.
  48. ^ [1] AVANTI AWARD IN LIPIDS
  49. ^ AAAS Membership
  50. ^ Royal Society of Edinburgh Prizes
  51. ^ EurekAlert! 7-Apr-2005
  52. ^ Karolinska Institute Archived 2011-07-18 at the Wayback Machine
  53. ^ "American professor awarded the Jacobæus Prize 2013 | Novo Nordisk Fonden". www.novonordiskfonden.dk. Archived from the original on 2016-03-04. Retrieved 2016-01-05.
  54. ^ "Dr. Lewis C. Cantley and Dr. Catherine Lord Elected to the Institute of Medicine of the National Academies". Weill Cornell Medical College. Retrieved 2016-01-05.
  55. ^ "Dr. Lewis Cantley Honored With the 2015 AACR Princess Takamatsu Memorial Lectureship | Sandra and Edward Meyer Cancer Center". meyercancer.weill.cornell.edu. Retrieved 2016-01-05.
  56. ^ "Molecular Medicine Awards 3rd Annual Ross Prize to Dr. Lewis C. Cantley, Cancer Researcher at Weill Cornell Medical College and NY Presbyterian Hospital - The Feinstein Institute for Medical Research". The Feinstein Institute for Medical Research. Retrieved 2016-01-05.
  57. ^ "Lewis Cantley | Gairdner". www.gairdner.org. Retrieved 2016-01-05.
  58. ^ "Cantley elected to EMBO | Sandra and Edward Meyer Cancer Center". meyercancer.weill.cornell.edu. Retrieved 2016-01-05.
  59. ^ "Lewis Cantley to receive 2015 AACI distinguished scientist award | Sandra and Edward Meyer Cancer Center". meyercancer.weill.cornell.edu. Retrieved 2016-01-05.
  60. ^ "Eloqua - Error Information" (PDF). images.info.science.thomsonreuters.biz. Retrieved 2016-01-22.
  61. ^ "Weill Cornell's Cantley wins Wolf Prize in Medicine | Cornell Chronicle". www.news.cornell.edu. Retrieved 2016-01-22.
  62. ^ Louisa Gross Horwitz Prize 2019
  63. ^ "Is Sugar Toxic? 60 Minutes report". YouTube. Archived from the original on 2012-05-01.

External links

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