Prognostic Factors, Predictive Markers and Cancer Biology: The Triad for Successful Oral Cancer Chemoprevention

Abstract

Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers. A major global health concern, oral squamous cell carcinoma (OSCC) is currently the 13th most common cancer worldwide, with an estimate of 300,000 new cases, and 145,000 deaths each year [1]. Tobacco, alcohol and/or betel nut exposure are well-established risk factors for OSCC. Interruption of carcinogen use is an obvious key intervention to reduce oral cancer incidence ('primary' prevention). Nonetheless, OSCC risk remains elevated even after alcohol and tobacco cessation and may take up to 20 years to reach baseline levels [2] illustrating the need for development of approaches that can interrupt/reverse the process of carcinogenesis after initiation, but before full malignant transformation. Furthermore, an increase in the incidence of oral cancer in women with no clear etiologic factors has been observed [3], supporting the need for improved understanding of molecular pathways dysregulation that lead to cancer and how they could be targeted for OSSC prevention.Oral potentially malignant lesions (OPMLs) are often clinically characterized as leukoplakia and/or erythroplakia. Histologically, these lesions frequently exhibit hyperplasia, hyperkeratosis and/or varying degrees of dysplasia (i.e., intraepithelial neoplasias [IEN]). OPMLs are not obligate precursors of oral cancers, but they are estimated to precede development of at least 7% of OSCC [4] OPMLs are in and of themselves risk factors for oral cancer, but have a variable frequency of malignant transformation, depending on other clinical, demographic, etiologic, histological and/or molecular features [5]. The anatomic accessibility of OPMLs for examination and biopsies provides an opportunity for clinical and translational studies of oral carcinogenesis. In this review, we will summarize the recent advances and future perspectives of molecularly focused strategies of oral cavity cancers chemoprevention, many of which stem from OPML-based research. We will specifically

Clinico-pathological prognosticators in oral squamous cell carcinoma

“…A working classification along with some of the markers with prognostic significance is listed in Table 3. [117][118][119][120][121][122][123] It is observed that site-wise distribution of OSCC is responsible for intra and inter-tumoural heterogeneity. In this regard, some authors studied buccal mucosa and tongue OSCC for possible heterogeneity in the cell cycle regulatory mechanism by comparing major cell cycle regulatory proteins.…”

Ki-67 Prognostic Value in Different Histological Grades of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

“…until now, a panel of molecular markers has not been determined that allows for a prognostic prediction of oral squamous cell carcinoma. However, these new markers could be considered complementary to conventional prognostic evaluation (Monteiro de Oliveira Novaes and William, 2016).…”

Identification of Proteomic Markers in Head and Neck Cancer Using MALDI–MS Imaging, LC–MS/MS, and Immunohistochemistry

“…In the context of precision medicine approaches for the treatment of HNC, MALDI-MSI is capable of supporting the strategy of integrating molecular prognostic and predictive marker and cancer biology. [42] Our study reveals the potential MALDI-MSI holds for clinical applications. In contrast to classical histopathological methods, it makes it possible to detect different markers in one tissue section and with a single measurement.…”

“…In the context of precision medicine approaches for the treatment of HNC, MALDI–MSI is capable of supporting the strategy of integrating molecular prognostic and predictive marker and cancer biology …”