TY - JOUR
T1 - Investigational agents to enhance the efficacy of chemotherapy or radiation in pancreatic cancer
AU - Hurtado, Myrna
AU - Sankpal, Umesh T.
AU - Ranjan, Amalendu
AU - Maram, Rajasekhar
AU - Vishwanatha, Jamboor K.
AU - Nagaraju, Ganji Purnachandra
AU - El-Rayes, Bassel F.
AU - Basha, Riyaz
N1 - Funding Information:
This work is partially supported by Shirley E. Noland Foundation grant awarded to RB and a grant ( #2U54MD006882-06 ) awarded to Dr. JKV from the National Institute of Minority Health and Health Disparities .
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/6
Y1 - 2018/6
N2 - Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays. Cur has a low level of toxicity and promising anti-cancer activity, however, its clinical development has been limited by low bioavailability. Cur analogs and nanoparticles were synthesized to improve Cur's efficacy and bioavailability. These compounds were found to be effective in enhancing the therapeutic effects of chemotherapy in pre-clinical models. Small molecules such as NSAIDs have also been tested for the anti-cancer activity and induction of response of chemotherapy and radiation. Interest in TA, a NSAID, has recently increased due to promising preclinical data demonstrating its anti-cancer properties with minimum toxicity. TA also synergistically increased the response of XRT in PC cells and in an orthotropic mouse model. With strong preclinical evidence, research aimed at developing less toxic therapies for PC using Cur analogues or TA is ready for translation into clinical testing.
AB - Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays. Cur has a low level of toxicity and promising anti-cancer activity, however, its clinical development has been limited by low bioavailability. Cur analogs and nanoparticles were synthesized to improve Cur's efficacy and bioavailability. These compounds were found to be effective in enhancing the therapeutic effects of chemotherapy in pre-clinical models. Small molecules such as NSAIDs have also been tested for the anti-cancer activity and induction of response of chemotherapy and radiation. Interest in TA, a NSAID, has recently increased due to promising preclinical data demonstrating its anti-cancer properties with minimum toxicity. TA also synergistically increased the response of XRT in PC cells and in an orthotropic mouse model. With strong preclinical evidence, research aimed at developing less toxic therapies for PC using Cur analogues or TA is ready for translation into clinical testing.
KW - Chemotherapy
KW - Combination treatment
KW - Pancreatic cancer
KW - Radiation
UR - http://www.scopus.com/inward/record.url?scp=85046131662&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2018.03.016
DO - 10.1016/j.critrevonc.2018.03.016
M3 - Review article
C2 - 29759562
AN - SCOPUS:85046131662
SN - 1040-8428
VL - 126
SP - 201
EP - 207
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
ER -