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Melanoma Resistance to Photodynamic Therapy

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Resistance to Photodynamic Therapy in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 5))

Abstract

Melanoma is a dreaded form of skin cancer caused by the malignant transformation of skin melanocytes and can be highly aggressive and has a rapidly growing incidence and elevated mortality and a poor prognosis at an advanced stage. Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches are being developed. Photodynamic therapy (PDT) has shown promising results for the treatment of different types of cancer. This therapy involves administration of a photosensitizer (PS), which on excitation after suitable irradiation generates singlet oxygen and other cytotoxic reactive oxygen species (ROS), thus, killing the cancer cells. Unfortunately, melanoma is considered to be resistant to PDT. There are many different reasons for this resistance including: (1) optical interference by melanin; (2) the anti-oxidant effect of melanin (3) sequestration of PS inside melanosomes (4) efflux of PS by multi-drug transporters and (5) errors in apoptotic pathways. Various approaches to overcome this PDT resistance of melanoma are being evaluated such as the use of agents that overcome the apoptotic defects, or hinder the efflux of PS, or use of methods to reduce the quantity or the pigmentation of the melanin. The introduction of highly active PS absorbing in the 700–800 nm near infrared (NIR) spectral region, and new advances in two-photon excitation of PS, together with PS linked to upconverting nanoparticles may overcome the optical interference of melanin. Finally, employing immunotherapy and, thus, exploiting the ability of PDT to activate the host immune system against the treated tumor, may also play a role in allowing PDT to overcome resistant melanomas.

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Acknowledgments

Research in the Hamblin laboratory is supported by US NIH grant R01AI050875.

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Authors and Affiliations

  1. Wellman Center for Photomedicine, Massachusetts General Hospital, 02114, Boston, MA, USA

    Sulbha K Sharma, Ying-Ying Huang & Michael R Hamblin

  2. Raja Ramanna Centre for Advanced Technology, Indore, India

    Sulbha K Sharma

  3. Department of Dermatology, Harvard Medical School, 02115, Boston, MA, USA

    Ying-Ying Huang & Michael R Hamblin

  4. Harvard-MIT Division of Health Sciences and Technology, 02139, Cambridge, MA, USA

    Michael R Hamblin

Authors
  1. Sulbha K Sharma
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  2. Ying-Ying Huang
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Correspondence to Michael R Hamblin .

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Editors and Affiliations

  1. Medical and Biological Sciences, University of Udine, Udine, Italy

    Valentina Rapozzi

  2. Prof. Ghiretti, Universita Padova Ist. Biologia Animale, Padova, Italy

    Giulio Jori

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Sharma, S., Huang, YY., Hamblin, M. (2015). Melanoma Resistance to Photodynamic Therapy. In: Rapozzi, V., Jori, G. (eds) Resistance to Photodynamic Therapy in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-319-12730-9_11

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