This review summarizes actual clinical needs in oncology that can be addressed by Raman spectroscopy, provides results published in the last 10 years and analyses the current status of translation of these results into clinical practice.

Clinical diagnosis of early melanoma (Breslow thickness less than 0.8 mm) is crucial to disease-free survival. However, it is subjective and can be exceedingly difficult, leading to missed melanomas, or unnecessary excision of benign pigmented skin lesions. An objective technique is needed to improve the diagnosis of early melanoma. We have developed a method to improve diagnosis of (thin) melanoma, based on Raman spectroscopy. In an ex vivo study in a tertiary referral (pigmented lesions) centre, high-wavenumber Raman spectra were collected from 174 freshly excised melanocytic lesions suspicious for melanoma. Measurements were performed on multiple locations within the lesions. A diagnostic model was developed and validated on an independent data set of 96 lesions. Approximately 60% of the melanomas included in this study were melanomas in situ. The invasive melanomas had an average Breslow thickness of 0.89 mm. The diagnostic model correctly classified all melanomas (including in situ) with a specificity of 43.8%, and showed a potential improvement of the number needed to treat from 6.0 to 2.7, at a sensitivity of 100%. This work signifies an important step towards accurate and objective clinical diagnosis of melanoma and in particular melanoma with Breslow thickness <0.8 mm.

In 2020, approximately 10 million people died of cancer, rendering this disease the second leading cause of death worldwide. Detecting cancer in its early stages is paramount for patients’ prognosis and survival. Hence, the scientific and medical communities are engaged in improving both therapeutic strategies and diagnostic methodologies, beyond prevention. Optical vibrational spectroscopy has been shown to be an ideal diagnostic method for early cancer diagnosis and surgical margins assessment, as a complement to histopathological analysis. Being highly sensitive, non-invasive and capable of real-time molecular imaging, Raman and Fourier transform infrared (FTIR) spectroscopies give information on the biochemical profile of the tissue under analysis, detecting the metabolic differences between healthy and cancerous portions of the same sample. This constitutes tremendous progress in the field, since the cancer-prompted morphological alterations often occur after the biochemical imbalances in the oncogenic process. Therefore, the early cancer-associated metabolic changes are unnoticed by the histopathologist. Additionally, Raman and FTIR spectroscopies significantly reduce the subjectivity linked to cancer diagnosis. This review focuses on breast and head and neck cancers, their clinical needs and the progress made to date using vibrational spectroscopy as a diagnostic technique prior to surgical intervention and intraoperative margin assessment.

(1) Breast cancer is presently the leading cause of death in women worldwide. This study aims at identifying molecular biomarkers of cancer in human breast cancer cells, in order to differentiate highly aggressive triple-negative from non-triple-negative cancers, as well as distinct triple-negative subtypes, which is currently an unmet clinical need paramount for an improved patient care. (2) Raman and FTIR (Fourier transform infrared) microspectroscopy state-of-the-art techniques were applied, as highly sensitive, specific and non-invasive methods for probing heterogeneous biological samples such as human cells. (3) Particular biochemical features of malignancy were unveiled based on the cells’ vibrational signature, upon principal component analysis of the data. This enabled discrimination between TNBC (triple-negative breast cancer) and non-TNBC, TNBC MSL (mesenchymal stem cell-like) and TNBC BL1 (basal-like 1) and TNBC BL1 highly metastatic and low-metastatic cell lines. This specific differentiation between distinct TNBC subtypes—mesenchymal from basal-like, and basal-like 1 with high-metastatic potential from basal-like 1 with low-metastatic potential—is a pioneer result, of potential high impact in cancer diagnosis and treatment.