Head and neck squamous cell carcinomas (HNSCCs) represent the most common epithelial tumors that arise from mucosa of the oral cavity, pharynx, and larynx. The development of HNSCCs is usually associated with tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Most HNSCCs are diagnosed in advanced states, leading to a worse clinical outcome. Screening tests based on potential biomarkers associated with HNSCCs could improve this scenario. Liquid biopsy has emerged as a promising area of cancer investigation, offering a minimally invasive approach to track circulating biomarkers in body fluids that could potentially contribute to the diagnosis, predict prognosis, and monitor response to treatment. This review will discuss translational studies describing the clinical applications of liquid biopsy in HPV-negative and HPV-positive HNSCCs focused on circulating nucleic acids [cell-free DNA (cfDNA) and cell-free RNA (cfRNA)], circulating tumor cells (CTCs), and extracellular vesicles (EVs), which can be found in plasma, serum, and saliva.

The dynamic spectrum of microRNA (miRNA) has grown significantly over the years with its identification and exploration in cancer therapeutics and is currently identified as an important resource for innovative strategies due to its functional behavior for gene regulation and modulation of complex biological networks. The progression of cancer is the consequence of uncontrolled, nonsynchronous procedural faults in the biological system. Diversified and variable cellular response of cancerous cells has always raised challenges in effective cancer therapy. miRNAs, a class of non-coding RNAs (ncRNAs), are the natural genetic gift, responsible to preserve the homeostasis of cell to nurture. The unprecedented significance of endogenous miRNAs has exhibited promising therapeutic potential in cancer therapeutics. Currently, miRNA mimic miR-34, and an antimiR aimed against miR-122 has entered the clinical trials for cancer treatments. This review, highlights the recent breakthroughs, challenges, clinical trials, and advanced delivery vehicles in the administration of miRNA therapies for precision oncology.

Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells, which are expanded in most cancer patients. MDSCs suppress host immune responses, leading to cancer growth and progression. Several studies demonstrated that there was a relationship between levels of MDSCs and tumorigenesis in colorectal cancer (CRC) patients. MDSCs are now being investigated for their role as possible therapeutic targets in cancer treatment. This review summarizes available studies that investigated MDSC expansion in CRC patients, as well as their role in CRC tumorigenesis, prognosis, and targeting. Based on the available studies, there is a possible relationship between high levels of MDSCs and CRC progression. Additionally, targeting MDSCs in CRC patients selectively represents a significant challenge for the development of targeted treatments. Targeting of MDSCs could be exploited in different ways including MDSC depletion, inhibition of MDSC function and recruitment, and enhancing MDSC differentiation. Overall, MDSCs could be exploited as prognostic biomarkers and potential therapeutic targets in CRC.

Endocrine resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. When abnormally regulated, molecular signals responsible for cellular proliferation, as well as ER itself, allow for cellular evasion of ER-dependent treatments. Therefore, pharmacological treatments that target these evasion mechanisms are beneficial for the treatment of endocrine-resistant breast cancers. This review summarizes currently understood molecular signals that contribute to endocrine resistance and their crosstalk that stem from mitogen-activated protein kinase (MAPK), phosphoinositol-3 kinase/protein kinase B (PI3K/AKT), mechanistic target of rapamycin (mTOR), cyclin-dependent kinases 4 and 6 (CDK4/6) and aberrant ER function. Recent clinical trials that target these molecular signals as a treatment strategy for endocrine-resistant breast cancer are also highlighted.

Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that is still uncurable. The therapies used to treat the disease target immune activity, inhibit proteasome activity, and involve the use of monoclonal antibodies. However, MM is a highly heterogeneous disease, in fact, there are several mutations in signaling pathways that are particularly important for MM cell biology and that are possible therapeutic targets. Indeed, some studies suggest that MM is driven by mutations within the rat sarcoma virus (RAS) signaling cascade, which regulates cell survival and proliferation. The RAS/proto-oncogene, serine/threonine kinase (RAF)/mitogen-activated extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway is deregulated in several cancers, for which drugs have been developed to inhibit these pathways. In addition to the signaling pathways, the disease implements mechanisms to ensure the survival and consequently a high replicative capacity. This strategy consists in the deregulation of apoptosis. In particular, some cases of MM show overexpression of anti-apoptotic proteins belonging to the B cell lymphoma 2 (BCL-2) family that represent a possible druggable target. Venetoclax is an anti-BCL-2 molecule used in hematological malignancies that may be used in selected MM patients based on their molecular profile. We focused on the possible effects in MM of off-label drugs that are currently used for other cancers with the same molecular characteristics. Their use, combined with the current treatments, could be a good strategy against MM.

Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hypercalcemia, pathologic fractures, spinal cord compression, and even death. However, the underlying mechanisms of bone metastasis were not clear. The role of calcium (Ca²⁺) in cancer cell proliferation, migration, and invasion has been well established. Interestingly, emerging evidence indicates that Ca²⁺ signaling played a key role in bone metastasis, for it not only promotes cancer progression but also mediates osteoclasts and osteoblasts differentiation. Therefore, Ca²⁺ signaling has emerged as a novel therapeutical target for cancer bone metastasis treatments. Here, the role of Ca²⁺ channels and Ca²⁺-binding proteins including calmodulin and Ca²⁺-sensing receptor in bone metastasis, and the perspective of anti-cancer bone metastasis therapeutics via targeting the Ca²⁺ signaling pathway are summarized.

With the rapid development of gene therapy technology and the outbreak of coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) therapeutics have attracted more and more attention, and the COVID-19 mRNA vaccine has been approved by the Food and Drug Administration (FDA) for emergency authorization. To improve the delivery efficiency of mRNA in vitro and in vivo, researchers have developed a variety of mRNA carriers and explored different administration routes. This review will systematically introduce the types of mRNA vectors, routes of administration, storage methods, safety of mRNA therapeutics, and the type of diseases that mRNA drugs are applied for. Finally, some suggestions are supplied on the development direction of mRNA therapeutic agents in the future.

Compared to humans, plants can synthesize an extremely diverse array of chemical compounds, including phenolic acids, flavonoids, stilbenes, lignans, terpenoids, alkaloids, and many other types of secondary metabolites that have been demonstrated to exert important bioactivities and impacts on the human health. As a result of extensive and sustained efforts, some phytochemicals like vincristine, vinblastine, and paclitaxel have already been approved as anticancer drugs today, while several others are under clinical trials. However, despite this remarkable success, studies on anticancer action of plant-derived products have been and paradoxically are still in some places, mixed up with alternative approaches and thereby considered non-credible, especially in regions where the role of traditional medicine has not been historically so prevalent as in several Asian countries. As a result, only about 10% of higher plants have been explored regarding the potential therapeutic effects of their constituents. Moreover, as one function of secondary metabolites includes the protection of plants against diverse environmental stresses, the content and composition of these phytochemicals might importantly vary between different regional habitats. Therefore, the stereotyped attitudes to plant products as something related to alternative medicine must be changed to identify new lead molecules for novel anticancer drugs. It is possible that plants still harbor an important spectrum of pharmaceutically interesting, but still unidentified, chemical compounds.