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Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tum

The Dynamic Role of Curcumin in Mitigating Human Illnesses: Recent Advances in Therapeutic Applications.

Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effectiveness, accessibility, and minimal risk of adverse effects. Curcuma longa L., commonly known as turmeric, exemplifies such herbal remedies with its extensive history of culinary and medicinal applications across Asia for thousands of years. Traditionally utilized as a dye, flavoring, and in cultural rituals, turmeric has also been employed to treat a spectrum of medical conditions, including inflammatory, bacterial, and fungal infections, jaundice, tumors, and ulcers. Building on this longstandin

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… Chin D. Wagner A.E. Rimbach G. Curcumin—From Molecule to Biological Function Angew. Chem. Int. Ed. 2012 51 5308 5332 10.1002/anie.201107724 22566109 9. Venkateswarlu S. Ramachandra M.S. Subbaraju G.V. Synthesis and Biological Evaluation of Polyhydroxycurcuminoids Bioorg. Med. …

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

The current socioeconomic and regulatory landscape of immune effector cell therapies.

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T ce

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… Lee L, Draper B, Chaplin N, Philip B, Chin M, Galas-Filipowicz D, et al. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. (2018) 131:746–58. doi: 10.1182/blood-2017-05-781351, PMID: 50. …

Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serio

H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.

During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as

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… Chin H. G. Benner J. Feehery G. R. Samaranayake M. Horwitz G. A. ( 2009 ). Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells . Proc. Natl. Acad. Sci. 106 ( 13 ), 5076 – 5081 . 10.1073/pnas.0810362106 19282482 PMC2654809 Etani T. Suzuki T. Naiki T. …

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review.

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The c

The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.

Cancer is caused by abnormal proliferation of cells and aberrant recognition of the immune system. According to recent studies, natural products are most likely to be effective at preventing cancer without causing any noticeable complications. Among the bioactive flavonoids found in fruits and vegetables, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties. This review aims to highlight the potential therapeutic effects of quercetin on some different types of cancers including blood, lung and prostate cancers.

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox

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… Chin. Med. J. 2021;134:1897–1907. doi: 10.1097/CM9.0000000000001628. 68. Kumar S., Yedjou C.G., Tchounwou P.B. Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells. J. Exp. Clin. …

Localized Drug Delivery Systems: An Update on Treatment Options for Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, with surgery, radiotherapy, chemotherapy, and immunotherapy being the primary treatment modalities. The treatment for HNSCC has evolved over time, due to which the prognosis has improved drastically. Despite the varied treatment options, major challenges persist. HNSCC chemotherapeutic and immunotherapeutic drugs are usually administered systemically, which could affect the patient's quality of life due to the associated side effects. Moreover, the systemic administration of salivary stimulating agent

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies.

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic dr

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… Two-photon imaging of lymphoma cells targeted by gold nanoparticles Chin. Opt. Lett. 2008 6 879 881 84. Moghiseh M. Lowe C. Lewis J.G. Kumar D. Butler A. Anderson N. Raja A. …

Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabo

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… Ali A, Levantini E, Teo JT, Goggi J, Clohessy JG, Wu CS, Chen L, Yang H, Krishnan I, Kocher O, Zhang J, Soo RA, Bhakoo K, Chin TM, Tenen DG. Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer. EMBO Mol Med. 2018. 10(3) 91. …

Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.

Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, h…

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

Emerging Therapies in the Management of Advanced-Stage Gastric Cancer.

Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer. The Cancer Genome Atlas (TCGA) pr

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… Chin K. Lee K.-W. Park S. H. Rha S. Y. ( 2017 ) Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial . J. Clin. …

Cellular immunotherapy in melanoma: the next frontier in cancer treatment.

Therapy-resistant melanoma remains a major clinical challenge despite advances with immune checkpoint inhibitors and targeted therapies, as most patients ultimately exhibit primary or acquired resistance and progress through multiple toxic treatment lines with limited durable benefit. This resistance reflects not only T-cell dysfunction but also a profound quantitative deficit of tumor-reactive lymphocytes, compounded by myeloid- and Treg-mediated immunosuppression, impaired antigen presentation, and tumor dedifferentiation programs generating a cold tumor microenvironment. Cellular immunother

Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell qual

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

Comprehensive review of targeted therapy for colorectal cancer.

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents

Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer.

The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields … cation. As drug efficacy remains the main bottleneck for overall success, we discuss the need for machine-learning computational methods in combination with specific phenotypic studies along with mechanistic studies, chemical genetics and omics assays to successfully predict disease-drug pairs. Such a pipeline could be particularly important to cancer …