Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy

TY - JOUR

T1 - Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy

AU - Viktorsson, Kristina

AU - Rieckmann, Thorsten

AU - Fleischmann, Maximilian

AU - Diefenhardt, Markus

AU - Hehlgans, Stephanie

AU - Rödel, Franz

N1 - © 2023. The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - Recent advances in understanding the tumor's biology in line with a constantly growing number of innovative technologies have prompted characterization of patients' individual malignancies and may display a prerequisite to treat cancer at its patient individual tumor vulnerability. In recent decades, radiation- induced signaling and tumor promoting local events for radiation sensitization were explored in detail, resulting the development of novel molecular targets. A multitude of pharmacological, genetic, and immunological principles, including small molecule- and antibody-based targeted strategies, have been developed that are suitable for combined concepts with radiation (RT) or chemoradiation therapy (CRT). Despite a plethora of promising experimental and preclinical findings, however, so far, only a very limited number of clinical trials have demonstrated a better outcome and/or patient benefit when RT or CRT are combined with targeted agents. The current review aims to summarize recent progress in molecular therapies targeting oncogenic drivers, DNA damage and cell cycle response, apoptosis signaling pathways, cell adhesion molecules, hypoxia, and the tumor microenvironment to impact therapy refractoriness and to boost radiation response. In addition, we will discuss recent advances in nanotechnology, e.g., RNA technologies and protein-degrading proteolysis-targeting chimeras (PROTACs) that may open new and innovative ways to benefit from molecular-targeted therapy approaches with improved efficacy.

AB - Recent advances in understanding the tumor's biology in line with a constantly growing number of innovative technologies have prompted characterization of patients' individual malignancies and may display a prerequisite to treat cancer at its patient individual tumor vulnerability. In recent decades, radiation- induced signaling and tumor promoting local events for radiation sensitization were explored in detail, resulting the development of novel molecular targets. A multitude of pharmacological, genetic, and immunological principles, including small molecule- and antibody-based targeted strategies, have been developed that are suitable for combined concepts with radiation (RT) or chemoradiation therapy (CRT). Despite a plethora of promising experimental and preclinical findings, however, so far, only a very limited number of clinical trials have demonstrated a better outcome and/or patient benefit when RT or CRT are combined with targeted agents. The current review aims to summarize recent progress in molecular therapies targeting oncogenic drivers, DNA damage and cell cycle response, apoptosis signaling pathways, cell adhesion molecules, hypoxia, and the tumor microenvironment to impact therapy refractoriness and to boost radiation response. In addition, we will discuss recent advances in nanotechnology, e.g., RNA technologies and protein-degrading proteolysis-targeting chimeras (PROTACs) that may open new and innovative ways to benefit from molecular-targeted therapy approaches with improved efficacy.

U2 - 10.1007/s00066-023-02064-y

DO - 10.1007/s00066-023-02064-y

M3 - SCORING: Review article

C2 - 37041372

VL - 199

SP - 1091

EP - 1109

JO - STRAHLENTHER ONKOL

JF - STRAHLENTHER ONKOL

SN - 0179-7158

IS - 12

ER -