News Research integrity

Dario Altieri remembers Filippo Giancotti

The sad state of affairs of oncology drug discovery

On 14 July 2023, the great Italian-born US cancer researcher Filippo Giancotti died, only two years after leaving MD Anderson Cancer Center in Texas and joining Columbia University in New York as the new director of the Cancer Metastasis Initiative at the Herbert Irving Comprehensive Cancer Center (HICCC). Giancotti died relatively “young”, probably in his late 60ies. There were obituaries, here is one by his Columbia University, and here is one by another great Italian-born US cancer researcher, Dario Altieri:

Of integrins, signaling, and risotto

“Filippo Giancotti passed away last month in New York City from complications of biliary cancer. Educated as a physician-scientist at the University of Torino, Italy, Filippo had come to America in 1988 to train as a postdoctoral fellow in La Jolla, CA. That’s where I first met him. We were part of a small but boisterous group of Italian postdocs working on both sides of Torrey Pines Road. In essence, we were all the same. Self-starters and passionate about science, we were fundamentally no different from our ancestors coming to America a century earlier. We came by plane instead of a steamer, but we were all eager to leave behind the often tortuous and not always meritocratic academic world back home for something different, maybe even something better. […]

A gifted experimentalist, an innovator, and a cell biologist at heart, Filippo pioneered the role of integrins as multifunctional receptors, serving in intercellular adhesion but also in intercellular communication. He uncovered disparate signaling pathways coordinated by integrin engagement and unraveled profound implications of those pathways in cancer: from the control of epithelial-to-mesenchymal transition to modulation of tumor suppressors to acquisition and maintenance of metastatic competence. Published in the top journals for impact, not impact factor, Filippo’s work was innovative, thorough, and definitive. It stood the test of time and became the foundation of more research. It made careers for scores of young scientists who wanted to pursue a similar biology. Making it in integrin research in La Jolla was not easy: the place thought of itself as some sort of world capital of integrinology. Remaining relevant in the same field over the years was even harder. And yet, Filippo’s engine continued to have only one gear: forward. His work led the field for the next three decades, mostly at academic institutions in New York City with a relatively brief stint in Houston. Built over the decades through rigor and resilience, Filippo’s reputation was rock solid. Unassailable. […]

Filippo was a superb scientist. And an equally superb physician. He knew what he had. He knew the statistics. And he knew the sad state of affairs of oncology drug discovery.”

It is always tragic when someone dies of cancer. But here one should not blame the pharma industry on the sad state of oncology drug discovery. After all, the Big Pharma relies on peer reviewed academic discoveries of such Italo-American cancer research titans like Giancotti, Altieri, Carlo Croce, Pier-Paolo Pandolfi…

Maybe worth remembering that Giancotti used to be a collaborator of the legendary Italian fraudster Alfredo Fusco. One of their joint papers was retracted in 2018:

M T Berlingieri , G Manfioletti , M Santoro , A Bandiera , R Visconti , V Giancotti , A Fusco Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells Molecular and Cellular Biology (1995) doi: 10.1128/mcb.15.3.1545

22 years after its publication, the paper was retracted, this was the retraction notice from 2018 (highlights mine):

“The publisher hereby retracts this article. Questions have been raised by concerned readers about the integrity of the data. The American Society for Microbiology has reviewed the figures and confirmed evidence of apparent manipulation and duplication. Since the integrity of the data as presented was compromised, this publication is retracted in its entirety. We apologize to the readers of Molecular and Cellular Biology and regret any inconvenience that this causes. The authors did not agree to this retraction.

By 2018, everyone working in cancer research knew that Fusco was an utter fraud. And the journal most likely found many more forgeries than the Figure 8. Yet still, the great Giancotti insisted that his paper was perfectly fine and apparently that Fusco was an honest, unfairly maligned researcher.

It was also Giancotti’s own papers which were questioned. Sometimes he issued corrections, grudgingly, and only for problems already discovered. Like here:

Hua Gao , Goutam Chakraborty , Ai Ping Lee-Lim , Qianxing Mo , Markus Decker , Alin Vonica , Ronglai Shen , Edi Brogi , Ali H. Brivanlou , Filippo G. Giancotti The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites Cell (2012)   doi: 10.1016/j.cell.2012.06.035 

Corrected in 2012: “we inadvertently inserted an incorrect image in Figures 1H and S6A .
Giancotti on PubPeer: “The duplication was intentional as we meant to show a single cell dosage in Fig.1 and the full titration experiment in Fig.3. The robustness and statistical significance of the experiment is clear from the size of the cohorts and P values. In addition, this is a negative control meant to show that Coco does not affect primary tumor growth at non-limiting cell dosage. It would have been wasteful of federal funding to repeat the experiment just for inclusion of a second version of it in the paper.
Indigofera tanganyikensis:A mouse in Figure 1G (vector, 5 weeks) is identical to another mice in Figure 4C (ATO7-control, 3 weeks).”

Also this paper was corrected in 2019:

Tomoyo Okada , Surajit Sinha , Ilaria Esposito , Gaia Schiavon , Miguel A. López-Lago , Wenjing Su , Christine A. Pratilas , Cristina Abele , Jonathan M. Hernandez , Masahiro Ohara , Morihito Okada , Agnes Viale , Adriana Heguy , Nicholas D. Socci , Anna Sapino , Venkatraman E. Seshan , Stephen Long , Giorgio Inghirami , Neal Rosen , Filippo G. Giancotti The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling Nature Cell Biology (2019) doi: 10.1038/ncb3082 

The 2019 correction notice went:

“In the version of this Article originally published the same blot was inadvertently presented as both p-Rb and Cyclin A in Fig. 2a. This blot corresponds to the p-Rb panel, as can be seen in the unprocessed version of these blots in Supplementary Fig. 9. The corrected version of the panel is shown below, together with a completely uncropped image of both blots. In addition, in the ‘Viral transduction’ section of the Methods, the pLKO.1 plasmids encoding short hairpin RNAs targeting human Rnd1 were incorrectly listed as clones TRCN0000018338 and TRCN0000039977. The correct clone numbers are TRCN0000047434 and TRCN0000047435.”

That should presumably cover for the later discovered gel duplication in Figure 4, Giancotti must have decided:

It seems, Giancotti was never a big fan of issuing corrections, he only issued them when he really had to:

Michael Dans , Laurent Gagnoux-Palacios , Pamela Blaikie , Sharon Klein , Agnese Mariotti , Filippo G. Giancotti Tyrosine phosphorylation of the beta 4 integrin cytoplasmic domain mediates Shc signaling to extracellular signal-regulated kinase and antagonizes formation of hemidesmosomes Journal of Biological Chemistry (2001) doi: 10.1074/jbc.m008663200 

But then again, what’s the point of correction in cases like this:

Sotiris N. Nikolopoulos , Pamela Blaikie , Toshiaki Yoshioka , Wenjun Guo , Claudia Puri , Carlo Tacchetti , Filippo G. Giancotti Targeted deletion of the integrin beta4 signaling domain suppresses laminin-5-dependent nuclear entry of mitogen-activated protein kinases and NF-kappaB, causing defects in epidermal growth and migration Molecular and Cellular Biology (2005)   doi: 10.1128/mcb.25.14.6090-6102.2005 

Anyway, the paper was already corrected for a typo, so it should cover also later discovered image forgeries, no?

And what about Dario Altieri, President and CEO of The Wistar Institute in Philadelphia? Did his cancer research deliver?

Irene Bertolini , Michela Perego , Jagadish C. Ghosh , Andrew V. Kossenkov , Dario C. Altieri NFκB activation by hypoxic small extracellular vesicles drives oncogenic reprogramming in a breast cancer microenvironment Oncogene (2022) doi: 10.1038/s41388-022-02280-3

The freshly published paper was already corrected twice. In January 2023 correction we were informed by the journal:

“A panel of Figure 3 was inadvertently duplicated during the review process. In the originally published manuscript, the Vimentin panel of pXSC treatment after sEVNORM exposure was erroneously duplicated as the Vimentin panel of pXSC treatment after sEVHYP exposure.”

The second correction was issued in June 2023:

“In former Supplementary Fig. 6A, the top left panel was inadvertently mislabeled as “Control” when, in fact, corresponded to sEVHYP-exposed cells treated with the small molecule NFκB inhibitor, pXSC. The correct “Control” panel has now been included in a revised Supplementary Fig. 6A.”

Bullshitter Mauro Ferrari out as ERC President

Mauro Ferrari was made to resign as ERC president. In his 3 months in office, he published a ridiculously fraudulent paper with Houston colleagues. Now Ferrari announces from his Texas lockdown “trenches” to cure COVID-19.

But also Altieri is no fan of publishing corrections. Not even easy ones, for fresh papers:

Irene Bertolini , Jagadish C. Ghosh , Andrew V. Kossenkov , Sudheer Mulugu , Shiv Ram Krishn , Valentina Vaira , Jun Qin , Edward F. Plow , Lucia R. Languino, Dario C. Altieri Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment Developmental Cell (2020) doi: 10.1016/j.devcel.2020.07.014 

Actinopolyspora biskrensis: “The control images in Figure 1C appear to be unexpectedly similar for different cell lines, with an adjustment to brightness.”

This 10 year old papers needs one for sure. Maybe even a retraction:

Valentina Vaira , Alice Faversani , Nina M. Martin , David S. Garlick , Stefano Ferrero , Mario Nosotti , Joseph L. Kissil , Silvano Bosari, Dario C. Altieri Regulation of Lung Cancer Metastasis by Klf4-Numb–like Signaling Cancer Research (2013) doi: 10.1158/0008-5472.can-12-4232 (Fig 2 C and 2E)

The treatments may look same, but according to figure legends, those are different cell lines: Figure 2C shows “monolayers of A549 cells” and Figure 2E shows “breast adenocarcinoma MDA-MB231 cells”. Not likely to have been recycled by an honest mistake.

What exactly is the scientific value in this kind of research data?

Bing Z. Carter , Michele Milella , Dario C. Altieri , Michael Andreeff Cytokine-regulated expression of survivin in myeloid leukemia Blood (2001) doi: 10.1182/blood.v97.9.2784 

There is more on PubPeer, for both scientists, the late Giancotti and the live Altieri, and there likely will be even more if someone has a fresh look into their papers. I am not even showing the many inappropriately spliced gels here.

And here is yet another great Italian cancer researcher in USA, Antonio Giordano. This champion of research ethics is apparently trying to sue me in court in Italy:


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19 comments on “Dario Altieri remembers Filippo Giancotti

    • Another prominent cancer researcher leaves a dubious legacy, Jose Baselga.

      Not just failing to disclose corporate ties/ conflicts of interest,

      but quite a bit of problematic data, the science wasn’t so good.

      https://pubpeer.com/search?q=Jose+Baselga

      Try as they might “death-washing” doesn’t change the problematic data for others.

      Like

      • “And what about Dario Altieri, President and CEO of The Wistar Institute in Philadelphia? Did his cancer research deliver?”

        https://pubpeer.com/publications/F432F1B4244FADC94F0EE35EA5A4C9#1

        “The EPR-1 gene described in this paper appears to be a cloning artifact

        See Blood. 2000 Jul 1;96(1):145-8. The elusive factor Xa receptor: failure to detect transcripts that correspond to the published sequence of EPR-1 G J Zaman, E M Conway PMID: 10891443 “

        Like

    • Very famous deceased American, with very problematic data. The paper was not that old when the detailed comments began.
      Is this deeply flawed paper going to remain in the scientific record forever?

      https://pubpeer.com/publications/262782AAA2FE7464C4CE3641C71743#9

      Scroll up?

      Like

      • Obituary: “On February 24, 2019, the biomedical research community lost Dr. Arthur B. Pardee, whose numerous and diverse contributions to molecular and cancer biology will never be forgotten. In a field where most of us would be thrilled to make one major contribution, Art Pardee’s legacy is vast, having shaped disparate areas of research including enzymology, DNA repair, gene regulation, cell-cycle control, and novel technologies that ushered in the era of global gene expression profiling. “
        If his peers care so much for Art’s memory, why don#t they find out who faked this paper?

        Like

  1. “But then again, what’s the point of correction in cases like this:”

    Sotiris N. Nikolopoulos , Pamela Blaikie , Toshiaki Yoshioka , Wenjun Guo , Claudia Puri , Carlo Tacchetti , Filippo G. Giancotti Targeted deletion of the integrin beta4 signaling domain suppresses laminin-5-dependent nuclear entry of mitogen-activated protein kinases and NF-kappaB, causing defects in epidermal growth and migration Molecular and Cellular Biology (2005) doi: 10.1128/mcb.25.14.6090-6102.2005

    The cells are breeding on the page. 2, now 3.

    https://pubpeer.com/publications/2CFFF919AC221F9D7D49CB78194E61#2

    Like

  2. https://www.cuimc.columbia.edu/news/passing-filippo-giancotti-md-phd

    Third signatory obituary above , Gerard Karsenty, Columbia University, has these problematic data:

    https://pubpeer.com/search?q=Gerard+Karsenty+

    Like

  3. Columbia University, with the help of MIT, is a purveyor of vintage fraud. Wei Gu (Columbia University), and Leonard Guarente (MIT), are mere employees of the corporate Behemoths.

    https://pubpeer.com/publications/65ECC6CE97FC8FD6C8139C293F6064

    Like

    • NMH, the failed scientist and incel

      maybe we should build a wall to prevent the south americans from getting “trained” in the US.
      (possible from) Trump: “Is it possible to bomb Argentina, because of CONCEITed research”?

      What is it with italian/spanish/portaguese/greek “scientists”? WTF?

      Like

    • Same organisation as Vanesa Gottifredi (LeLoir).

      Mol Cell Biol. 2010 Mar; 30(5): 1285–1298.
      Published online 2009 Dec 28. doi: 10.1128/MCB.01190-09
      PMCID: PMC2820887
      PMID: 20038533
      The hsp90-FKBP52 Complex Links the Mineralocorticoid Receptor to Motor Proteins and Persists Bound to the Receptor in Early Nuclear Events▿
      Mario D. Galigniana,1,2 Alejandra G. Erlejman,2 Martín Monte,2 Celso Gomez-Sanchez,3 and Graciela Piwien-Pilipuk1,2,*
      Author information Article notes Copyright and License information PMC Disclaimer
      Instituto de Biología y Medicina Experimental/CONICET, Buenos Aires, Argentina,1 Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina,2 Division of Endocrinology, G. V. (Sonny) Montgomery VA Medical Center, and University of Mississippi Medical Center, Jackson, Mississippi3
      *Corresponding author. Present address: IBYME/CONICET, Vuelta de Obligado 2490, Buenos Aires C1428ADN, Argentina. Phone: 54 (11) 4783-2869. Fax: 54 (11) 4786-2564.
      E-mail: gppilipuk@leloir.org.ar

      https://pubpeer.com/publications/11001B97070C275419F1E6BF6F3AD4#1

      Like

    • What is the point of a review of a retracted paper?

      https://pubpeer.com/publications/255DB581E3B5B29C6061D377B0C273

      That’ll do nicely for Carol Prives!

      Why not retract the review?

      Like

  4. “In lumine Tuo videbimus lumen”.

    If only Columbia University could see the light in the first place before virtue-signalling motto.

    What a breath of fresh air if Columbia University were to review allegations about scientific fraud within its own walls, and come to a determination.

    Like

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