Data from Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery Article Swipe

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Huang‐Chiao Huang , Imran Rizvi , Joyce F. Liu , Sriram Anbil , Ashish Kalra , Helen Lee , Yan Baglo , Nancy Paz , Ivor S. Douglas , Stephen P. Pereira , Brian W. Pogue , Jonathan B. Fitzgerald , Tayyaba Hasan ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/0008-5472.c.6509981.v1

Physiologic barriers to drug delivery and selection for drug resistance limit survival outcomes in cancer patients. In this study, we present preclinical evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve drug delivery barriers in the tumor microenvironment to safely widen the therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal-IRI) prevented tumor relapse, reduced metastasis, and increased both progression-free survival and 1-year disease-free survival. PDP enabled these durable improvements by targeting multiple tumor compartments to (i) increase intratumoral drug accumulation by >10-fold, (ii) increase the duration of drug exposure above a critical therapeutic threshold, and (iii) attenuate surges in CD44 and CXCR4 expression, which mediate chemoresistance often observed after multicycle chemotherapy. Overall, our results offer preclinical proof of concept for the effectiveness of PDP to minimize risks of tumor relapse, progression, and drug resistance and to extend patient survival.Significance: A biophysical priming approach overcomes key treatment barriers, significantly reduces metastases, and prolongs survival in orthotopic models of human pancreatic cancer. Cancer Res; 78(2); 558–71. ©2017 AACR.

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Medicine Pancreatic cancer Irinotecan Metastasis Drug Drug delivery Cancer Tumor microenvironment Priming (agriculture) Drug resistance Tumor progression Cancer research Pharmacology Chemotherapy Oncology Internal medicine Chemistry Biology Colorectal cancer Microbiology Organic chemistry Botany Germination

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/0008-5472.c.6509981.v1
OA Status: gold
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OpenAlex ID: https://openalex.org/W4361235197

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DOI: https://doi.org/10.1158/0008-5472.c.6509981.v1

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Title: Data from Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-03-31

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Authors: Huang‐Chiao Huang, Imran Rizvi, Joyce F. Liu, Sriram Anbil, Ashish Kalra, Helen Lee, Yan Baglo, Nancy Paz, Ivor S. Douglas, Stephen P. Pereira, Brian W. Pogue, Jonathan B. Fitzgerald, Tayyaba Hasan

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Landing page: https://doi.org/10.1158/0008-5472.c.6509981.v1

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Concepts: Medicine, Pancreatic cancer, Irinotecan, Metastasis, Drug, Drug delivery, Cancer, Tumor microenvironment, Priming (agriculture), Drug resistance, Tumor progression, Cancer research, Pharmacology, Chemotherapy, Oncology, Internal medicine, Chemistry, Biology, Colorectal cancer, Microbiology, Organic chemistry, Botany, Germination

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abstract_inverted_index.observed	120
abstract_inverted_index.outcomes	12
abstract_inverted_index.prolongs	164
abstract_inverted_index.relapse,	65, 142
abstract_inverted_index.strategy	29
abstract_inverted_index.survival	11, 72, 165
abstract_inverted_index.(nal-IRI)	62
abstract_inverted_index.558–71.	176
abstract_inverted_index.attenuate	109
abstract_inverted_index.barriers,	159
abstract_inverted_index.combining	57
abstract_inverted_index.cytotoxic	48
abstract_inverted_index.increased	69
abstract_inverted_index.overcomes	156
abstract_inverted_index.patients.	15
abstract_inverted_index.prevented	63
abstract_inverted_index.selection	6
abstract_inverted_index.survival.	76
abstract_inverted_index.targeting	83
abstract_inverted_index.treatment	158
abstract_inverted_index.xenograft	52
abstract_inverted_index.irinotecan	61
abstract_inverted_index.multicycle	122
abstract_inverted_index.orthotopic	51, 167
abstract_inverted_index.pancreatic	55, 171
abstract_inverted_index.resistance	9, 146
abstract_inverted_index.threshold,	106
abstract_inverted_index.biophysical	153
abstract_inverted_index.expression,	115
abstract_inverted_index.metastases,	162
abstract_inverted_index.metastasis,	67
abstract_inverted_index.preclinical	21, 128
abstract_inverted_index.therapeutic	43, 105
abstract_inverted_index.>10-fold,	94
abstract_inverted_index.accumulation	92
abstract_inverted_index.compartments	86
abstract_inverted_index.disease-free	75
abstract_inverted_index.improvements	81
abstract_inverted_index.intratumoral	90
abstract_inverted_index.photodynamic	26
abstract_inverted_index.progression,	143
abstract_inverted_index.chemotherapy.	123
abstract_inverted_index.effectiveness	134
abstract_inverted_index.nanoliposomal	60
abstract_inverted_index.significantly	160
abstract_inverted_index.nanoformulated	47
abstract_inverted_index.subtumoricidal	25
abstract_inverted_index.<i>Cancer	173
abstract_inverted_index.chemoresistance	118
abstract_inverted_index.microenvironment	38
abstract_inverted_index.progression-free	71
abstract_inverted_index.AACR</i>.</p></div>	178
abstract_inverted_index.<div>Abstract<p>Physiologic	0
abstract_inverted_index.survival.</p><p><b>Significance:</b>	151
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	13
sustainable_development_goals[0].id	https://metadata.un.org/sdg/3
sustainable_development_goals[0].score	0.8199999928474426
sustainable_development_goals[0].display_name	Good health and well-being
citation_normalized_percentile.value	0.03494965
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False