Resistance mechanisms in photodynamic therapy
Kristian
Berg
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway
The therapeutic effects of PDT are in many cases encouraging although more frequently with a palliative than a curative end point. In this respect there is a need to search for factors that may limit the therapeutic outcome of PDT. Resistance mechanisms in the broad sense are a major limitation for a curative treatment end point for many diseases such as cancers and bacterial infections. The treatment resistance may be due to innate or acquired properties of the treated cells or tissue.
Several resistance mechanisms may influence the therapeutic outcome. A better understanding of these resistance mechanisms, prognostic markers for therapeutic outcome and adjuvant treatments and combination therapies to enhance the curative outcome of PDT are needed. This is the focus of this special issue of Photochemical & Photobiological Sciences which presents a comprehensive overview of this field and hopefully stimulates innovative preclinical and clinical PDT research.
In cancer, the target cells or tissue may have developed a phenotype that is intrinsically resistant to PDT, such as those related to the hallmarks of cancer as described by Hanahan and Weinberg.1 Hasan and coworkers provide an overview of how PDT may interact with the resistance mechanisms of cancer and provide an alternative to other exciting therapies (DOI: 10.1039/c4pp00495g). Resistance mechanisms may develop due to repeated treatments with alternative therapies such as radio- and chemotherapy as well as PDT itself, as described by Juarranz and coworkers (DOI: 10.1039/c4pp00448e). PDT may influence many of the intrinsic survival and growth signals of cancer cells such as NFκB (Piette, DOI: 10.1039/c4pp00465e), the double-edged sword nitric oxide (Girotti, DOI: 10.1039/c4pp00470a), autophagy (Agostinis and coworkers, DOI: 10.1039/c4pp00466c), anti-apoptotic signaling (Kessel, DOI: 10.1039/c4pp00413a), p53 (Acedo and Zawacka-Pankau, DOI: 10.1039/c5pp00251f), modifications of the cytoskeleton and adhesion proteins such as in epithelial-to-mesenchymal transition (Casas and coworkers, DOI: 10.1039/c4pp00445k) or subpopulations of cells such as cancer stem cells (Selbo et al., DOI: 10.1039/c5pp00027k). These mechanisms may have negative influences on the therapeutic outcome of current uses of PDT. However, increasing knowledge of these mechanisms may guide treatment modifications and adjuvant therapies to improve the therapeutic outcome, as described in this special issue. The photochemical treatment may also be used to enhance the therapeutic effect of other therapeutics, such as in photochemical internalization (Weyergang et al., DOI: 10.1039/c5pp00029g). A major cause of cancer development is the escape from T-cell recognition. Many of the established treatment regimens, such as surgery, ionizing radiation and chemotherapy, have no or only moderate stimulatory effects on T-cells, while the newly developed immune check-point inhibitors have shown encouraging results. PDT has been shown to induce T-cell mediated anti-tumor immunity in some clinical cases and in preclinical studies. Hamblin and coworkers (DOI: 10.1039/c4pp00455h) have described why it does not always work and how to improve it. The innate immune system also greatly influences tumor growth and macrophages have been shown to be important targets of PDT that may cause both anti- and pro-survival effects, as described by Korbelik and Hamblin (DOI: 10.1039/c4pp00451e. Therapeutic approaches to modify these responses for improved therapeutic outcome are described.
PDT is attractive as an alternative to antibiotics that, due to extensive use in recent years, have caused the development of resistant subpopulations. This is becoming a global health problem. Maisch (DOI: 10.1039/c5pp00037h) described the utilization of photodynamic antimicrobial chemotherapy (PACT) as an alternative to antibiotics and the impact of PACT on the surviving bacteria.
This special issue is dedicated to Professor Giulio Jori who sadly passed away on the 23rd of December 2014. He had a great impact on the development of many aspects of photodynamic therapy, as described in the obituary published in the July 2015 issue of Photochemical & Photobiological Sciences. We thank him for his contributions to the PDT field and photobiology in general, both scientifically and by his enthusiasm, and his memory will also stimulate our future photobiology activities.
References
| This journal is © The Royal Society of Chemistry and Owner Societies 2015 |