## 1 Introduction  
In the 1970s, cancer research was dominated by molecular genetics and biochemistry [1]. However, in most solid tumors, malignant cells coexist with noncancerous tissue [2]. In addition, it is now clear that cancer growth and progression are associated with the microenvironmental and physical abnormalities of cancer cells and tumors [3, 4, 5]. Recently, physical oncology was proposed and applied to investigate soft tissue tumors, given that the hardness of tumor cells has a significant influence on invasion and metastasis strategies [6].Tumor cells differ in chemoresistance with respect to hardness, organ site, and metastatic performance [7, 8, 9]. For example, tumor cell hardness is critical relative to the surrounding cells because tumor cells may be stiffer than the surrounding tissue and may push the surrounding tissue away. Moreover, they may be softer than the surrounding tissue and develop in the interstitial space. Thus, cancer cells are characterized by heterogeneity within the tumor, ranging from physical and mechanical changes in the extracellular matrix (ECM) [10]. Macroscopic bio-stiffness evaluation schemes in vivo are widely used. The evaluation of the elastic modulus using ultrasound elastography has been conducted in clinical practice as a noninvasive method for the measured organ structures [11, 12]. However, these techniques had a spatial resolution at the submillimeter scale and did not measure the elastic modulus of single cells wherein cell-to-cell interactions occur in the state of organ geometry. By contrast, microscopic in vitro measurement methods at the single-cell level are common. For example, micropipette aspiration is the most classical approach for measuring the mechanical properties of cells, cell nuclei, and tissues [13; 14; 15]. However, this technique has suffered from low throughput ranging from 180 s per cell, as indicated in studies published in the 1950s, [16] to 3.6 s per cell, as reported in the 1990s, [17]. Other methods, such as the magnetic tweezer assay [18], have been developed and utilized to measure DNA elasticity [19; 20; 21; 22]. In the same tweezer assay, the optical tweezer method [23] using laser light was developed in 1968 and is still widely used. In a previous study, the stiffness of cells was reported by measuring the elastic modulus of single cells under optical radiation pressure using a technique referred to as optical stretcher [7]. While tweezer assays can evaluate cells such as red blood cells [24], they are not suitable for all cells [25]. Furthermore, these techniques cannot be evaluated in organ geometry because of their approach to single cells. Atomic force microscope (AFM) has been utilized as a technique for microscopic cellular-level elasticity mapping while preserving organ geometry [26; 27; 28]. Using AFM on normal and malignant human breast biopsies, [PERSON] et al. found that in late-stage cancers there was more softening in the center and an increase in stiffness toward the periphery with sclerosis of the tumor stroma [29]. This study is a clear example in which elastic modulus mapping provided very effective information. However, methods to assess mechanical properties at the single-cell level, including AFM, require high-precision instrumentation and specialized training. Hopefully, these challenges can be overcome to assess cellular response non-destructively and continuously in situ [30]. Recently, laser-induced thermoelastic waves were studied as a diagnostic technique referred to as laser resonance frequency analysis (L-RFA) for the initial stability of orthopedic implant installations [31; 32; 33]. The principle of L-RFA is based on the measurement of the laser-induced photothermal elastic wave (LIPTEW) on implants such as pedicle screws and acetabular cups. The LIPTEW can lead to resonant vibration, which consists of an audible frequency region and employs the same scheme as the hammering test used for the concrete walls of tunnels and fastening bolts of bridges [34; 35].