Targeted multiplex proteomics towards more precisely matching patients to novel anti-cancer medicines

Recently published open access in Scientific Reports*, VHIO’s Paolo Nuciforo, Principal Investigator of our Molecular Oncology group, is Senior and Corresponding Author of an Article exploring the promise of using targeted multiplex proteomics (TMP) as a novel approach to simultaneously measure a panel of proteins implicated in oncogenic processes, tumor suppression, drug metabolism and resistance.

Also including tumor differentiation markers, this tool could guide standard diagnostic decision-making as well as render the selection of new targeted therapies and immune-based therapeutics for patients with metastatic colorectal cancer (mCRC) more precise.

Lead authored by Garazi Serna, alongside co-authors Roberta Fasani and Jose Jimenez of VHIO’s Molecular Oncology Group, this elegant report begins by concisely reviewing the strengths and limitations of the current ‘gold standard’ in accurately measuring multi-proteins in experimental samples, immunoassay, and outlines the downside of applying targeted proteomics using selected reaction monitoring mass spectrometry (SRM-MS).

The researchers, also counting on the expertise of other VHIO investigators and groups as well as the Vall d´Hebron University Hospital’s Pathology Department which is directed by Santiago Ramón y Cajal, then proceed to describe their findings by superbly sub-chaptering each stage of their analyses. Representing the very first study to measure the impact of quantitative targeted proteomics in precision oncology against mCRC, they analyzed protein biomarker profiles and integrated the results obtained with the available clinical, pathological and genomic data towards advancing precious insights into predictive and prognostic makers.

Not only do their findings signpost that proteomics-steered drug development will expand treatment options for patients who are eligible to participate in early phase clinical trials, particularly considering the increasing emergence of promising antibody-drug conjugates (ADCs) and immune-based treatments, but also ring in the repurposing of proteomics as powerful anti-cancer armory in precision oncology.

Commenting for VHIO Communications Paolo Nuciforo said, “Our data shows that targeted multiplex proteomics constitutes a promising molecular screening tool in this particular patient population. Importantly, this new approach could represent a powerful contender in pinpointing protein expression alterations that could impact on patient outcomes and more precisely guide patient eligibility for inclusion in clinical trials.”

“We have re-affirmed the inter-tumor heterogeneity of colorectal cancer with unique protein alterations in individual cases. Our approach could more effectively guide patient enrolment in early phase clinical studies, and spur the co-development of biomarkers and novel agents against this tumor type,” added Garazi Serna, first author of this present study and PhD student of Paolo Nuciforo’s group.

“Based on our results thus far, our TMP panel including proteins as targets for ADCs and immune checkpoints will ultimately advance combinatorial immunotherapeutic strategies against colorectal cancer,”she concluded.

To access this present open access Article please click here.

For more information about this research contact Amanda Wren, Director of Communications at VHIO, via email: awren@vhio.net.

This research was supported by our Institutional Advanced Molecular Diagnostics Program (DIAMAV) which is powered by the FERO Foundation and co-led by VHIO’s Director, Josep Tabernero, in collaboration with Ana Vivancos, Paolo Nuciforo, and Rodrigo Dienstmann, Principal Investigators of our Cancer Genomics, Molecular Oncology, and Oncology Data Science (ODysSey) Groups, respectively.

We also acknowledge and gratefully thank the CELLEX Foundation for VHIO’s state-of-the-art research facilities and scientific equipment.

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*Serna G, Ruiz-Pace F, Cecchi F, Fasani R, Jimenez J, Thyparambil S, Landolfi S, Elez E, Vivancos A, Hembrough T, Tabernero J, Dienstmann R, Nuciforo P.Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer. Sci Rep. 2019 Sep 19;9(1):13568. doi: 10.1038/s41598-019-49867-7.