Roles for receptor tyrosine kinases in tumor progression and implications for cancer treatment

Soma Ghosh, Ilaria Marrocco, Yosef Yarden

Research output: Chapter in Book/Report/Conference proceedingChapter


Growth factors and their receptor tyrosine kinases (RTKs), a group of transmembrane molecules harboring cytoplasm-facing tyrosine-specific kinase functions, play essential roles in migration of multipotent cell populations and rapid proliferation of stem cells' descendants, transit amplifying cells, during embryogenesis and tissue repair. These intrinsic functions are aberrantly harnessed when cancer cells undergo intertwined phases of cell migration and proliferation during cancer progression. For example, by means of clonal expansion growth factors fixate the rarely occurring driver mutations, which initiate tumors. Likewise, autocrine and stromal growth factors propel angiogenesis and penetration into the newly sprouted vessels, which enable seeding micro-metastases at distant organs. We review genetic and other mechanisms that preempt ligand-mediated activation of RTKs, thereby supporting sustained cancer progression. The widespread occurrence of aberrant RTKs and downstream signaling pathways in cancer, identifies molecular targets suitable for pharmacological intervention. We list all clinically approved cancer drugs that specifically intercept oncogenic RTKs. These are mainly tyrosine kinase inhibitors and monoclonal antibodies, which can inhibit cancer but inevitably become progressively less effective due to adaptive rewiring processes or emergence of new mutations, processes we overview. Similarly important are patient treatments making use of radiation, chemotherapeutic agents and immune checkpoint inhibitors. The many interfaces linking RTK-targeted therapies and these systemic or local regimens are described in details because of the great promise offered by combining pharmacological modalities.

Original languageEnglish
Title of host publicationAdvances in Cancer Research
EditorsRakesh Kumar, Paul B. Fisher
PublisherAcademic Press Inc.
Number of pages57
ISBN (Print)9780128201428
StatePublished - 2020

Publication series

NameAdvances in Cancer Research
ISSN (Print)0065-230X

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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