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Chemotherapy-Induced Neuropathy and Drug Discovery Platform Using Human Sensory Neurons Converted Directly from Adult Peripheral Blood.

Chemotherapy-induced peripheral neuropathy (PN) is a disorder damaging the peripheral nervous system (PNS) and represents one of the most common side effects of chemotherapy, negatively impacting the quality of life of patients to the extent of withdrawing life-saving chemotherapy dose or duration. Unfortunately, the pathophysiological effects of PN are poorly understood, in part due to the lack of availability of large numbers of human sensory neurons (SNs) for study. Previous reports have demonstrated that human SNs can be directly converted from primitive CD34+ hematopoietic cells, but was

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.

Currently, chemotherapy is the main treatment for tumors, but there are still problems such as unsatisfactory chemotherapy results, susceptibility to drug resistance, and serious adverse effects. Natural compounds have numerous pharmacological activities which are important sources of drug discovery for tumor treatment. The combination of chemotherapeutic drugs and natural compounds is gradually becoming an important strategy and development direction for tumor treatment. In this paper, we described the role of natural compounds in combination with chemotherapeutic drugs in synergizing, reduci

Assessment tools for peripheral neuropathy in multiple myeloma.

Advances in treating multiple myeloma (MM) have improved survival, shifting the management focus toward quality of life. Peripheral neuropathy (PN) is a common treatment-related toxicity that significantly impairs quality of life. However, standardized assessment methods for PN in patients with MM are currently lacking. A comprehensive search of multiple databases (PubMed, Embase, Cochrane Library, and KoreaMed) was conducted to identify relevant records. Eligible studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-

Consensus on the Treatment and Follow-Up for Metastatic Castration-Resistant Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PurposeTo present a summary of the recommendations for the treatment and follow-up for metastatic castration-resistant prostate cancer (mCRPC) as acquired through a questionnaire administered to 99 physicians working in the field of prostate cancer in developing countries who attended the Prostate Cancer Consensus Conference for Developing Countries.MethodsA total of 106 questions out of more than 300 questions addressed the use of imaging in staging mCRPC, treatment recommendations across availability and response to prior drug treatments, appropriate drug treatments, and follow-up, and those

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… compounds as appropriate treatment options in the setting of limited healthcare resources and in men with mCRPC who progressed on or after docetaxel. … A systematic search on electronic databases evaluated the role of platinum compounds for mCRPC and suggested a statistically significant increase in both clinical as well biochemical response when adding platinum compounds to chemotherapy. 38 Similarly, oral cyclophosphamide was favored by 64.47% of …

Биологические движущие силы инъекции периферальной Neurophy в Множестве миеломы.

Внедрение иммуноводных препаратов (ИМИД), таких, как талидомид, линалидомид и помалидомид, привело к значительному улучшению методов лечения миеломы (ММ). Многие пациенты в настоящее время живут 10 или более лет со своим заболеванием, в результате чего побочные эффекты, связанные с лечением, приобретают все большее значение. Периферальная нейропатия (PN) является общим побочным эффектом терапии IMID, которая оказывает существенное воздействие на качество жизни пациентов, и в настоящее время не имеется никаких профилактических или целевых терапевтических стратегий. В ходе этого обзора изучаются

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… PN developing after treatment initiation is classified as chemotherapy‐induced PN (CIPN), commonly associated with anti‐myeloma agents such as IMiDs and Bortezomib, as well as platinum compounds and anti‐tubulins [ 27 , 35 ]. … They are dependent on intact retrograde axonal transport | Ion channel dysfunction (e.g., sodium, calcium or potassium) | Altered excitability, increased neuropathic pain signalling | Neuropathic pain signalling: upregulation TRPVs (animal model, all IMiDs) | CIPN (e.g., platinum compounds, bortezomib …

Current Management and the New Paradigm for ALK+ NSCLC After CROWN.

The 7-year update of the phase 3 CROWN study is the most impressive milestone in anaplastic lymphoma kinase (ALK)+ non-small-cell lung cancer (NSCLC) since the discovery of the oncogene 20 years ago and inaugurates an entire new paradigm. The progression-free survival (PFS) plateau at a high level > 50%, with an estimated very low annual progression rate < 2% after the third year, suggests that lorlatinib can inactivate the disease in most patients. The complete abrogation of on-target resistance abolishes ALK tyrosine kinase inhibitor (TKI) sequencing and will seriously impact future drug dev

Bisphosphonate conjugation for bone specific drug targeting.

Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types. The bisphosphonate molecule class binds specifically to hydroxyapatite and inhibits

The Proliferative and Apoptotic Landscape of Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is an aggressive molecular subtype that represents up to 15% of breast cancers. It occurs in younger patients, and typically shows rapid development of locoregional and distant metastasis, resulting in a relatively high mortality rate. Its defining features are that it is positive for basal cytokeratins and, epidermal growth factor receptor and/or c-Kit. Problematically, it is typically negative for the estrogen receptor and human epidermal growth factor receptor 2 (HER2), which means that it is unsuitable for either hormone therapy or targeted HER2 therapy. As

Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates.

Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs inco

A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapeutic agents cause many short and long term toxic side effects to peripheral nervous system (PNS) that drastically alter quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and enduring disorder caused by several anti-neoplastic agents. CIPN typically presents with neuropathic pain, numbness of distal extremities, and/or oversensitivity to thermal or mechanical stimuli. This adverse side effect often requires a reduction in chemotherapy dosage or even discontinuation of treatment. Currently there are no effective treatment options for CIPN. While the under

Targeting FGFR for cancer therapy.

The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current

Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use.

In the current chapter, a new strategic compilation of phytochemicals with potent antitumor properties has been addressed, most importantly focusing on cell cycle arrest and apoptotic signaling mechanism. A promising approach in tumor prevention is to eliminate cancer cells preferably via cell cycle arrest and programmed cell death with lesser harm to neighboring normal cells. Cancer cells have a survival advantage to escape apoptosis and relentlessly divide to proliferate, gearing up the cell cycle process. Recently, the use of phytochemical-derived conjugated chemotherapeutic agents has incr

Analysis of patient reported outcomes included in the registrational clinical trials of nivolumab for advanced non-small cell lung cancer.

In the era of value-based oncology care, stakeholders are increasingly using patient reported outcomes (PROs) to guide clinical and regulatory decisions. PROs are also included in health technology assessments to guide patient access, drug reimbursement and pricing. We reviewed PROs collected in the United States Food and Drug Administration approved indications of nivolumab in advanced NSCLC. We analyzed the PRO data reported in the CheckMate 9LA (NCT03215706), CheckMate 227 (NCT02477826), CheckMate 057 (NCT01673867), and CheckMate 017 (NCT01642004) registrational clinical trials, and conclud

Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that f

Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.

Antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs) are modular targeted therapeutics in which molecular recognition is coupled with controlled payload delivery. Owing to their high specificity and precision, they have been regarded as a transformative paradigm for cancer therapy. In this review, current understandings and future perspectives of ADCs and PDCs are synthesized across rational design principles, historical evolution, clinical translation, and emerging formats, aiming to improve practical comprehension and application in oncology. Key determinants of performance: ta

Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.

BACKGROUND: Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems. AIMS/OBJECTIVES: This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and o

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

Antibody drug conjugate: the "biological missile" for targeted cancer therapy.

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreove

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review.

Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors

An overview of randomized phase III clinical trials of cancer nanomedicines.

BackgroundCancer therapy has undergone significant advances in recent decades attributed to personalized medicine and targeted drug delivery. Among the promising approaches, the use of nano-based delivery systems has become a relevant approach capable of improving treatment by releasing antineoplastic drugs at the target site, improving therapeutic efficacy, minimizing cytotoxicity in healthy tissues, and ultimately, reducing the intensity of adverse effects of chemotherapy. This study prospectively evaluated the impact of formulating anti-neoplastic drugs as nanomedicines on clinical response