TY - JOUR
T1 - Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy
AU - Makinde, Adeola Y.
AU - Eke, Iris
AU - Aryankalayil, Molykutty J.
AU - Ahmed, Mansoor M.
AU - Coleman, C. Norman
N1 - Publisher Copyright:
© 2016
PY - 2016/10/1
Y1 - 2016/10/1
N2 - The dramatic changes in the technological delivery of radiation therapy, the repertoire of molecular targets for which pathway inhibitors are available, and the cellular and immunologic responses that can alter long-term clinical outcome provide a potentially unique role for using the radiation-inducible changes as therapeutic targets. Various mathematical models of dose and fractionation are extraordinarily useful in guiding treatment regimens. However, although the model may fit the clinical outcome, a deeper understanding of the molecular and cellular effect of the individual dose size and the adaptation to repeated exposure, called multifraction (MF) adaptation, may provide new therapeutic targets for use in combined modality treatments using radiochemotherapy and radioimmunotherapy. We discuss the potential of using different radiation doses and MF adaptation for targeting transcription factors, immune and inflammatory response, and cell “stemness.” Given the complex genetic composition of tumors before treatment and their adaptation to drug treatment, innovative combinations using both the pretreatment molecular data and also the MF-adaptive response to radiation may provide an important role for focused radiation therapy as an integral part of precision medicine and immunotherapy.
AB - The dramatic changes in the technological delivery of radiation therapy, the repertoire of molecular targets for which pathway inhibitors are available, and the cellular and immunologic responses that can alter long-term clinical outcome provide a potentially unique role for using the radiation-inducible changes as therapeutic targets. Various mathematical models of dose and fractionation are extraordinarily useful in guiding treatment regimens. However, although the model may fit the clinical outcome, a deeper understanding of the molecular and cellular effect of the individual dose size and the adaptation to repeated exposure, called multifraction (MF) adaptation, may provide new therapeutic targets for use in combined modality treatments using radiochemotherapy and radioimmunotherapy. We discuss the potential of using different radiation doses and MF adaptation for targeting transcription factors, immune and inflammatory response, and cell “stemness.” Given the complex genetic composition of tumors before treatment and their adaptation to drug treatment, innovative combinations using both the pretreatment molecular data and also the MF-adaptive response to radiation may provide an important role for focused radiation therapy as an integral part of precision medicine and immunotherapy.
UR - http://www.scopus.com/inward/record.url?scp=84995530495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995530495&partnerID=8YFLogxK
U2 - 10.1016/j.semradonc.2016.07.001
DO - 10.1016/j.semradonc.2016.07.001
M3 - Review article
C2 - 27619247
AN - SCOPUS:84995530495
SN - 1053-4296
VL - 26
SP - 254
EP - 260
JO - Seminars in Radiation Oncology
JF - Seminars in Radiation Oncology
IS - 4
ER -