Molecular Subtypes and the Evolution of Treatment Decisions in Metastatic Colorectal Cancer

American Society of Clinical Oncology Educational Book
Rodrigo DienstmannJosep Tabernero

Abstract

Colorectal cancer (CRC) has clinically relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics, and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations define a population refractory to epidermal growth factor receptor monoclonal antibodies, BRAFV600E mutations associate with poor outcomes under standard therapies and response to targeted inhibitors in combinations, and HER2 amplifications confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to epidermal growth factor receptor monoclonal antibodies have been described, with substantial overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment-refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential pre...Continue Reading

References

Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Jul 6, 2014·Clinical Chemistry·Stephen J SalipanteColin C Pritchard
Sep 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pierre Laurent-PuigValerie Taly
Jan 22, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemFortunato Ciardiello
Feb 24, 2015·Nature Genetics·Alexandre CalonEduard Batlle
May 15, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R Dienstmann, A Cervantes
Jul 8, 2015·Nature Medicine·Giulia SiravegnaAlberto Bardelli
Oct 10, 2015·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Emanuele ValtortaMarcello Gambacorta
Oct 13, 2015·Nature Medicine·Justin GuinneySabine Tejpar
Dec 4, 2015·British Journal of Cancer·Alessio AmatuSalvatore Siena
Mar 30, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Zsofia K StadlerLeonard B Saltz
Jul 28, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anne TrinhLouis Vermeulen
Dec 9, 2016·Nature Communications·Beth O Van EmburghAlberto Bardelli
Dec 21, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Andrea Sartore-BianchiSalvatore Siena
Jan 5, 2017·Nature Reviews. Cancer·Rodrigo DienstmannJosep Tabernero
Feb 10, 2017·Translational Oncology·Chen WangSusan P Lees-Miller
Feb 12, 2017·Journal of the National Comprehensive Cancer Network : JNCCN·Jun GongMarwan Fakih
Apr 4, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J GrasselliA Vivancos
Apr 19, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J VidalC Montagut
May 10, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeremy C JonesAxel Grothey
Jul 7, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas Tuxen PoulsenMichael Kragh
Sep 8, 2017·Nature Communications·Rina M MbofungPatrick Hwu
Oct 19, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C CremoliniF Pietrantonio
Oct 19, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Sanz-GarciaJ Tabernero
Dec 16, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anita SveenRagnhild A Lothe
Jan 11, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John D HainsworthRazelle Kurzrock
Jan 26, 2018·Journal of the National Cancer Institute·Filippo PietrantonioChiara Cremolini
Nov 1, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Sanz-GarciaJ Tabernero

❮ Previous
Next ❯

Citations

Jun 25, 2020·Scientific Reports·Angela Kallenbach-ThieltgesKlaus Gerwert
Jul 19, 2020·Nature Reviews. Gastroenterology & Hepatology·Henrik PetrowskyPierre-Alain Clavien
Dec 2, 2020·International Journal of Molecular Sciences·Angela DjananiManuel Maglione
Oct 18, 2020·Biomedicines·Ugo TestaElvira Pelosi
Dec 4, 2020·Clinical Colorectal Cancer·Atul BatraWinson Y Cheung
May 1, 2021·Cancers·Davide CiardielloErika Martinelli
Jul 25, 2021·International Journal of Molecular Sciences·Guido GiordanoMatteo Landriscina
Aug 28, 2021·Der Chirurg; Zeitschrift für alle Gebiete der operativen Medizen·Stefanie Nöpel-DünnebackeMichael Ghadimi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.