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Discrimination and Characterization of Heterocellular Populations Using Quantitative Imaging Techniques
Published on: June 30, 2017
Moving from histological subtyping to molecular characterization: new treatment opportunities in advanced
Simona Carnio1, Silvia Novello, Paolo Bironzo
1Department of Oncology, S. Luigi Hospital, University of Torino, Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
Abstract:
Over the last 10 years, the systemic treatment of advanced non-small-cell lung cancer has progressively moved away from the 'one-size-fits-all' approach to histological subtyping. Currently, there is a progressive implementation of targeted therapies based on specific molecular characteristics such as the EGF receptor sensitizing mutations and the anaplastic lymphoma kinase rearrangements. Despite the availability of effective agents against these abnormalities, acquired resistance is still a major issue. A new generation of tyrosine kinase inhibitors for EGF receptor and anaplastic lymphoma kinase targeting acquired resistance mechanisms have been recently investigated. Several promising tyrosine kinase inhibitors that hit other targets are also in clinical development, including: rat sarcoma gene/MEK, BRAF1, PIK3A, c-mesenchymal-epithelial transition, c-ros oncogene 1, rearranged during transfection, human EGFR 2, FGFR, VEGFR, PDGFR and discoidin death receptor 2. Furthermore, new advances in immunology have been achieved through the discovery of vaccines and immune checkpoint pathways such as the cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1 and its ligands.
Insights
Systemic treatment for advanced non-small-cell lung cancer now uses targeted therapies based on molecular characteristics. New tyrosine kinase inhibitors and immunotherapies are being developed to overcome treatment resistance and improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Systemic treatment for advanced non-small-cell lung cancer (NSCLC) has shifted from a uniform approach to one based on histological subtyping.
- Targeted therapies focusing on specific molecular alterations, like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, are increasingly used.
- Acquired resistance to existing targeted therapies remains a significant challenge in NSCLC management.
Purpose of the Study:
- To review the evolution of systemic treatment for advanced NSCLC.
- To highlight the development of new targeted therapies and immunotherapies.
- To discuss strategies for overcoming acquired resistance in NSCLC.
Main Methods:
- Review of current literature on targeted therapies and immunotherapies for NSCLC.
- Analysis of emerging drug candidates and their mechanisms of action.
- Discussion of clinical development pathways for novel treatments.
Main Results:
- A new generation of tyrosine kinase inhibitors (TKIs) targeting acquired resistance mechanisms for EGFR and ALK are under investigation.
- Several promising TKIs targeting other pathways, including RAS/MEK, BRAF, PIK3CA, MET, ROS1, HER2, FGFR, VEGFR, PDGFR, and DDR2, are in clinical development.
- Advances in cancer immunology have led to the discovery of vaccines and immune checkpoint inhibitors (e.g., targeting CTLA-4, PD-1/PD-L1).
Conclusions:
- The treatment landscape for advanced NSCLC is rapidly evolving with personalized medicine approaches.
- Next-generation TKIs and immunotherapies offer new hope for patients, particularly those with acquired resistance.
- Continued research into molecular targets and immune pathways is crucial for improving NSCLC outcomes.
