Current Insights and Advancements in Head and Neck Cancer: Emerging Biomarkers and Therapeutics with Cues from Single Cell and 3D Model Omics Profiling

Abstract

Head and neck cancer (HNC) is among the ten leading malignancies worldwide, with India solely contributing one-third of global oral cancer cases. The current focus of all cutting-edge strategies against this global malignancy are directed towards the heterogeneous tumor microenvironment that obstructs most treatment blueprints. Subsequent to the portrayal of established information, the review details the application of single cell technology, organoids and spheroid technology in relevance to head and neck cancer and the tumor microenvironment acknowledging the resistance pattern of the heterogeneous cell population in HNC. Bioinformatic tools are used for study of differentially expressed genes and further omics data analysis. However, these tools have several challenges and limitations when analyzing single-cell gene expression data that are discussed briefly. The review further examines the omics of HNC, through comprehensive analyses of genomics, transcriptomics, proteomics, metabolomics, and epigenomics profiles. Patterns of alterations vary between patients, thus heterogeneity and molecular alterations between patients have driven the clinical significance of molecular targeted therapies. The analyses of potential molecular targets in HNC are discussed with connotation to the alteration of key pathways in HNC followed by a comprehensive study of protein kinases as novel drug targets including its ATPase and additional binding pockets, non-catalytic domains and single residues. We herein review, the therapeutic agents targeting the potential biomarkers in light of new molecular targeted therapies. In the final analysis, this review suggests that the development of improved target-specific personalized therapies can combat HNC’s global plight.

Oxygen-releasing nanodroplets relieve intratumoral hypoxia in head and neck cancer spheroids.

“…The cells in the spheroids grow in multiple layers, forming aggregates and leading to the formation of zones, namely an outer proliferating zone, a middle quiescent viable zone, and an inner hypoxic to necrotic core. 6,72 The formation of different zones results in differential distribution of oxygen, nutrients, and growth factors and ultimately leads to heterogeneous uptake of drugs and drug resistance.…”

“…3,4 At the molecular level, HNC exhibits substantial heterogeneity, with diverse genetic alterations and dysregulated signaling pathways contributing to its aggressive behavior and therapeutic resistance. [5][6][7][8][9][10] Additionally, hypoxia, a hallmark of solid tumors, 11,12 plays a pivotal role in shaping the tumor microenvironment (TME) and compromising treatment outcomes in HNC. Hypoxic conditions within tumors arise due to the rapid proliferation of cancer cells and inadequate supply of oxygen from the aberrant tumor vasculature.…”

“…Conventional 2D monolayer models do not provide the complexity of tumor heterogeneity and architectures, while animal models can resemble actual tumor environments but lack high throughput and are difficult to control. 6,46,47 Three dimensional multicellular tumor spheroid models are a promising alternative that bridges the gap between traditional 2D monolayer cultures and in vivo animal models. Spheroids are self-assembled, multicellular aggregates grown in suspension that mimic tumor heterogeneity and complex architectures.…”

Identifying Biomarkers and Therapeutic Targets by Multiomic Analysis for HNSCC: Precision Medicine and Healthcare Management

“…The heterogeneity and relapsing nature of head and neck cancer require an improved understanding of the tumor nature in order to counteract the resistance, recurrence, and disparities in therapeutic response. 9 The failure in early diagnosis is due to a lack of suitable diagnostic biomarkers for screening and diagnosis. 10 Thus, new biomarkers for earlier detection as well as targeted therapies are essential for precision medicine.…”

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

“…Further improvements in prognosis and QOL in the malignancy are dependent upon the discovery of the disease-specific molecules or genomic alterations that can be used as therapeutic targets and powerful predictive biomarkers of individual response to the therapy, which could lead to precision medicine with truly active drug targets [ 6 , 9 , 15 – 17 ]. Omics research has been increasing the understanding of molecular basis underlying the disease [ 18 – 20 ]. Even so, the great heterogeneity of both clinical and biological characteristics, including the status with or without human papillomavirus infection, becomes a big obstacle to elucidate the cancer-specific mechanisms and the critical action molecules in hypopharyngeal cancer [ 1 , 6 , 9 , 10 ].…”