Tuesday, June 6, 2023
SCIENMAG: Latest Science and Health News
No Result
View All Result
  • Login
  • HOME PAGE
  • BIOLOGY
  • CHEMISTRY AND PHYSICS
  • MEDICINE
    • Cancer
    • Infectious Emerging Diseases
  • SPACE
  • TECHNOLOGY
  • CONTACT US
  • HOME PAGE
  • BIOLOGY
  • CHEMISTRY AND PHYSICS
  • MEDICINE
    • Cancer
    • Infectious Emerging Diseases
  • SPACE
  • TECHNOLOGY
  • CONTACT US
No Result
View All Result
Scienmag - Latest science news from science magazine
No Result
View All Result
Home SCIENCE NEWS Cancer

MYC inhibition halts metastatic breast cancer progression by blocking tumor growth, invasion & seeding

February 22, 2022
in Cancer
0
Share on FacebookShare on Twitter

 

Laura Soucek

Credit: Vall d’Hebron Institute of Oncology (VHIO).

  • VHIO-led research published in Cancer Research Communications shows that the first-in-class MYC inhibitor Omomyc effectively halts disease progression in metastatic breast cancer, from seeding to cancer cell spread, in vitro and in vivo.
  • For the first time, the investigators show that MYC inhibition by Omomyc dramatically reduces both primary and metastatic growth in breast cancer.
  • By demonstrating the applicability of Omomyc against metastatic breast cancer, with particular focus on the triple-negative subtype, results challenge the controversial notion that MYC inhibition could induce tumor cell invasion and metastasis.
  • The validation of the Omomyc mini-protein for the treatment of metastatic disease could ring in a new therapeutic opportunity for patients suffering from triple-negative breast cancer.

 

Published in Cancer Research Communications (1), a journal of the American Association for Cancer Research (AACR), findings reported by investigators of the Vall d’Hebron Institute of Oncology’s (VHIO) Models of Cancer Therapies Group (Vall d’Hebron Barcelona Hospital Campus), and VHIO-born spin-off Peptomyc S.L., show that MYC inhibition is anti-metastatic in breast cancer.

The deregulation of the pleiotropic and ubiquitous MYC oncoprotein is implicated in almost all human cancers, and while its role as a promoter of tumorigenesis is beyond doubt, its function in the process of metastasis remains controversial. Contrasting reports suggest both a pro-metastatic and anti-metastatic function of MYC have largely precluded research assessing MYC inhibitors in the metastatic setting.

Thanks to two decades of research pioneered by Laura Soucek and her team, as well as the dedicated work of other groups, MYC inhibition is gaining pace in entering the clinic. Historically considered as an undruggable target, MYC now officially occupies a top spot on the most-wanted list of targets in cancer therapy.

Having shown potent anti-tumor activity of the MYC inhibitor Omomyc in multiple cancer cell lines and mouse models, regardless of their tissue of origin or driver mutations, Laura’s group and her Peptomyc team are developing viable, non-toxic pharmacological options for MYC targeting in the clinic.

“Considering the results of our previous studies that have clearly demonstrated Omomyc’s efficacy in primary tumors, we hypothesized that targeting MYC could also be efficacious against metastatic breast cancer,” said Laura Soucek, corresponding author of this present study, Co-Founder & Chief Executive Officer (CEO) of Peptomyc, and an ICREA Research Professor.

Ringing in MYC inhibition in the metastatic setting

Metastases are genetically unstable. Information from a patient’s primary tumor might not mirror the metastasis, and one metastasis may vary from another, thus hampering the benefits of targeted therapies. Based on their data indicating the efficacy of MYC inhibition independently of the mutational profile of the tumor, the investigators hypothesized that this approach could overcome th challenge.

They also sought to establish if MYC inhibition could revert MYC’s promotion of epithelial-mesenchymal transition (EMT) and dedifferentiation, two important hallmarks of cancer metastasis.

The promise of Omomyc as a potential anti-metastatic therapy in breast cancer

To evaluate Omomyc’s efficacy against breast cancer and metastasis, the researchers used a panel of breast cancer cell lines, representative of all molecular subtypes of the disease. Assessing the transgenically expressed Omomyc first, they observed therapeutic impact in these cell lines and in cell-derived in vivo xenograft models.

They then confirmed that the same therapeutic impact can be achieved pharmacologically using the purified Omomyc mini-protein which demonstrated efficacy in cell lines in vitro, as well as in vivo, in cell-derived and patient-derived xenograft (PDX) models.

Results of this present study (1) shed important light on the efficacy of MYC inhibition in the metastatic setting, with particular focus on triple-negative breast cancer (TNBC). The investigators demonstrate for the first time that MYC inhibition by Omomyc is effective against TNBC by displaying potent anti-metastatic activity in vivo.

“Our results illuminate the relevance of MYC inhibition in metastatic disease, and are particularly timely now that MYC inhibitors, including our first Omomyc-derived compound, OMO-103, are reaching the clinic,” added Laura Soucek.

Notably, OMO-103 entered clinical trials in May 2021, and is being tested in patients with various solid tumors in the Phase I/IIa MYCure study (2). 

“We have now demonstrated that MYC inhibition by Omomyc exerts a dramatic effect on the metastatic process, from tumor growth, invasion to seeding. Findings evidenced a striking reduction in both primary tumor and metastatic growth. In some cases, metastases were even eradicated,” said Daniel Massó-Vallés, first author of this study and a Postdoctoral Researcher and Project Manager at Peptomyc.

This study shows the promise of Omomyc as an anti-metastatic therapy against breast cancer and also challenges the controversial notion that MYC inhibition potentiates, rather than inhibits, tumor cell invasion and metastasis.

Results support the inclusion of metastatic TNBC patients in the ongoing MYCure trial, uphold MYC’s essential role in all aspects of tumorigenesis, and could ultimately lead to improved survival in this patient population.

This research was carried out in collaboration with investigators from other VHIO groups including Violeta Serra (PI, Experimental Therapeutics Group), and Joaquín Arribas (PI, Growth Factors Group), and researchers at CIEMAT (Madrid, Spain), and the Karolinska Institutet (Stockholm, Sweden). 

This project was mainly funded by grants received from the Agència de Gestió d’Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants), Spanish Ministry of Science and Innovation, Spanish Ministry of Science and Technology – Institute of Health Carlos III, European Research Council (ERC), and the FERO Foundation.

 

###

References:

1. Daniel Massó-Vallés, Marie-Eve Beaulieu, Toni Jauset, Fabio Giuntini, Mariano F. Zacarías-Fluck, Laia Foradada, Sandra Martínez-Martín, Erika Serrano, Génesis Martín- Fernández, Sílvia Casacuberta-Serra, Virginia Castillo Cano, Jastrinjan Kaur, Sergio López- Estévez, Miguel Ángel Morcillo, Mohammad Alzrigat, Loay Mahmoud, Antonio Luque-García, Marta Escorihuela, Marta Guzman, Joaquín Arribas, Violeta Serra, Lars-Gunnar Larsson, Jonathan R. Whitfield & Laura Soucek. MYC inhibition halts metastatic breast cancer progression by blocking growth, invasion and seeding. Cancer Res Commun. 2022;2:110–30. doi: 10.1158/2767-9764.CRC-21-0103.

 

2. Phase 1/2 Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours (MYCure). ClinicalTrials.gov Identifier: NCT04808362.

 



Journal

Cancer Research Communications

DOI

10.1158/2767-9764.CRC-21-0103

Article Title

MYC inhibition halts metastatic breast cancer progression by blocking growth, invasion and seeding

Article Publication Date

21-Feb-2022

COI Statement

DMV, TJ, LF, SMM, GMF, SCS, VCC and SLE are or have been employees of Peptomyc S.L. LS and MEB are founders of Peptomyc S.L. and inventors of the European patent application #EP13382167.8 “METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER” (March 2013). MEB, MZF, LF, SCS, JRW and LS are shareholders of Peptomyc S.L. All other authors declare they have no conflict of interest.

Tags: blockingbreastcancergrowthhaltsinhibitioninvasionmetastaticMYCprogressionseedingtumor
Share26Tweet17Share5ShareSendShare
  • UTHSC Pangenome Researchers

    UTHSC researchers’ work on human pangenome aids understanding of common chromosomal abnormality

    75 shares
    Share 30 Tweet 19
  • Weather anomalies are keeping insects active longer

    67 shares
    Share 27 Tweet 17
  • Mount Sinai researchers use new deep learning approach to enable analysis of electrocardiograms as language

    65 shares
    Share 26 Tweet 16
  • Healthy vascular fat during menopause may stave off dementia later in life

    65 shares
    Share 26 Tweet 16
  • Renowned sociologist and Black Voices Quintet set to dazzle at HDR UK’s Black Internship Programme Opening Ceremony 2023

    65 shares
    Share 26 Tweet 16
  • ASCO: Targeted therapy achieves responses across multiple cancer types with FGFR alterations

    65 shares
    Share 26 Tweet 16
ADVERTISEMENT

About us

We bring you the latest science news from best research centers and universities around the world. Check our website.

Latest NEWS

UTHSC researchers’ work on human pangenome aids understanding of common chromosomal abnormality

Null results research now published by major behavioral medicine journal

Why expensive wine appears to taste better

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Join 206 other subscribers

© 2023 Scienmag- Science Magazine: Latest Science News.

No Result
View All Result
  • HOME PAGE
  • BIOLOGY
  • CHEMISTRY AND PHYSICS
  • MEDICINE
    • Cancer
    • Infectious Emerging Diseases
  • SPACE
  • TECHNOLOGY
  • CONTACT US

© 2023 Scienmag- Science Magazine: Latest Science News.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In