Anticancer drugs directed at single specific molecular targets tend to induce transitory responses, followed by relapses. Laser photobiomodulation may offer the possibility of targeting multiple hallmarks of cancer by using fit-for-purpose electromagnetic (EM) energy aiming to restore homeostasis-homeokinesis. 

Methods/Principal Findings: A literature search of English-language articles in five databases (Medline, ISI Web of Knowledge, Cochrane, Google Scholar, Scirus) was conducted using search terms relating to cancer (neoplasm, advanced cancer, palliative) in combination with photobiomodulation and/or low-level laser therapy (LLLT) in the period from January 1990 to January 2013. Controlled clinical trials with at least 1 year of follow up and minimum compliance of 90% were included. Clinical studies evaluating lymphedema, mucositis or pain were also included to illustrate post-LLLT responses to adverse effects of chemo-radiotherapy. In vitro and in vivo studies were considered as preliminary data for clinical trials. 

Retrieved articles suggest that photobiomodulation can modulate anti-tumor effects and reduce the adverse effects of chemo-radiotherapy. Results are discussed giving particular attention to two mechanistic proposals with potential anticancer applications, photo-infrared pulsed biomodulation (PIPBM) and water oscillator (WO). 

Conclusions/Significance: Translational research with laser photobiomodulation as a multi-target (multi-hallmark) therapy in cancer and other complex diseases appears warranted 

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