Adjuvant Biophysical Therapies in Osteosarcoma - PubMed (original) (raw)

Review

Adjuvant Biophysical Therapies in Osteosarcoma

Valeria Carina et al. Cancers (Basel). 2019.

Abstract

Osteosarcoma (OS) is a primary bone sarcoma, manifesting as osteogenesis by malignant cells. Nowadays, patients' quality of life has been improved, however continuing high rates of limb amputation, pulmonary metastasis and drug toxicity, remain unresolved issues. Thus, effective osteosarcoma therapies are still required. Recently, the potentialities of biophysical treatments in osteosarcoma have been evaluated and seem to offer a promising future, thanks in this field as they are less invasive. Several approaches have been investigated such as hyperthermia (HT), high intensity focused ultrasound (HIFU), low intensity pulsed ultrasound (LIPUS) and sono- and photodynamic therapies (SDT, PDT). This review aims to summarize in vitro and in vivo studies and clinical trials employing biophysical stimuli in osteosarcoma treatment. The findings underscore how the technological development of biophysical therapies might represent an adjuvant role and, in some cases, alternative role to the surgery, radio and chemotherapy treatment of OS. Among them, the most promising are HIFU and HT, which are already employed in OS patient treatment, while LIPUS/SDT and PDT seem to be particularly interesting for their low toxicity.

Keywords: adjuvant therapies; biophysical stimuli; osteosarcoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

OS genesis (A). Genetic alterations in germline or sporadic mutation in osteoblasts interfere with the osteogenic process, resulting in an alterate balance between proliferation and differentiation, that cause an uncontrolled cell proliferation. Standard OS treatment Flow Chart (B) according to the NCCN Clinical Practice Guidelines in Oncology Version I.2018.

Figure 2

Figure 2

Physical principles of adjuvant biophysical stimuli. HT treatment (A): The use of different type of HT source alone (alternating magnetic field (AMF) or radiofrequency (RF) or laser) causes a temperature increase reaching the maximum on the body surface that decreases while moving away from the source (Left Panel). The combined use with nanoparticles is able to concentrate the heat into target cells without heating the surrounding tissues (Right Panel). HIFU treatment (B): Thermal effect: the mechanical energy is converted into heat reaching the maximum temperature on tumor by focusing the US in a site-specific manner (Left Panel). Mechanical effect: focused ultrasound causes inertial cavitation, bubble explosion and ROS formation (Right Panel). LIPUS and SDT Treatment (C): LIPUS brings microstreaming improving membrane permeability and drugs uptake, moreover, in combination with sonosensitizer, triggers stable cavitation causing ROS generation. PDT treatment (D): The light beam excites photosensitizer electrons that, returning to the basal level, transmit the energy to nearby molecules inducing two type of reaction: (a) generation of reactive oxygen species (ROS) into the medium; (b) activation of singlet oxygen (1O2) promoting also ROS production.

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