Medical Oncology最新文献

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance. Trastuzumab could induce G1/G0 phase arrest by downregulating cyclin D3 protein expression. However, the protein expression of cyclin D3 was not affected in trastuzumab-resistant cells, which might be related to aberrant activation of ERK signaling pathway. Furthermore, degradation of cyclin D3 protein by trastuzumab was mainly resulted from ubiquitin-dependent proteasome mechanism instead of transcriptional regulation. In trastuzumab-resistant breast cancer cells, trastuzumab-induced degradation of cyclin D3 protein was abrogated. When the ubiquitin pathway was inhibited, cells would show a predisposition to resistance to trastuzumab. Further, CDK4/6 inhibitor can inhibit the proliferation of trastuzumab-resistant HER-2 positive breast cancer cells. Therefore, combination of CDK4/6 inhibitors and anti-HER2 targeted therapy may be an alternative and promising strategy to overcome trastuzumab resistance in the future.

This document was drafted by interdisciplinary experts informed by the evidence and guided by their extensive lymphedema clinical experience at the 2023 American Cancer Society (ACS) Lymphedema Summit: Forward Momentum: Future Steps in Lymphedema Management hosted by the ACS, Lymphology Association of North America, and the Washington School of Medicine  in St. Louis, Missouri. Consensus statements were derived from a facilitated workshop and multiple follow-up discussions and meetings combining available evidence and clinical expertise. The consensus statements find that the essential components of complete decongestive therapy (CDT) are examination, compression, manual techniques (this may include but is not limited to manual lymph drainage), exercise, skin care, education, and self-management. Adjunctive interventions and alternatives may complement CDT. CDT should be provided by specifically trained healthcare practitioners in lymphedema management, preferably a certified lymphedema therapist. The individual's lymphedema etiology and presentation, comorbidities, and other pertinent clinical information will determine the components of CDT applied and the frequency and duration of care.

Glioblastoma (GBM) is a highly prevalent and aggressive brain tumor in adults with limited treatment response, leading to a 5-year survival rate of less than 5%. Standard therapies, including surgery, radiation, and chemotherapy, often fall short due to the tumor's location, hypoxic conditions, and the challenge of complete removal. Moreover, brain metastases from cancers such as breast and melanoma carry similarly poor prognoses. Recent advancements in nanomedicine offer promising solutions for targeted GBM therapies, with nanoparticles (NPs) capable of delivering chemotherapy drugs or radiation sensitizers across the blood-brain barrier (BBB) to specific tumor sites. Leveraging the enhanced permeability and retention effect, NPs can preferentially accumulate in tumor tissues, where compromised BBB regions enhance delivery efficiency. By modifying NP characteristics such as size, shape, and surface charge, researchers have improved circulation times and cellular uptake, enhancing therapeutic efficacy. Recent studies show that combining photothermal therapy with magnetic hyperthermia using AuNPs and magnetic NPs induces ROS-dependent apoptosis and immunogenic cell death providing dual-targeted, immune-activating approaches. This review discusses the latest NP-based drug delivery strategies, including gene therapy, receptor-mediated transport, and multi-modal approaches like photothermal-magnetic hyperthermia combinations, all aimed at optimizing therapeutic outcomes for GBM.

Hepatocellular carcinoma (HCC) is a leading liver cancer that significantly impacts global life expectancy and remains challenging to treat due to often late diagnoses. Despite advances in treatment, the prognosis is still poor, especially in advanced stages. Studies have pointed out that investigations into the molecular mechanisms underlying HCC, including mitochondrial dysfunction and epigenetic regulators, are potentially important targets for diagnosis and therapy. Mitoepigenetics, or the epigenetic modifications of mitochondrial DNA, have drawn wide attention for their role in HCC progression. Besides, molecular biomarkers such as mitochondrial DNA alterations and non-coding RNAs showed early diagnosis and prognosis potential. Additionally, natural compounds like alkaloids, resveratrol, curcumin, and flavonoids show promise in HCC show promise in modulating mitochondrial and epigenetic pathways involved in cancer-related processes. This review discusses how mitochondrial dysfunction and epigenetic modifications, especially mitoepigenetics, influence HCC and delves into the potential of natural products as new adjuvant treatments against HCC.

In the spectrum of breast malignancies, triple-negative breast cancer is the most widely spreading subtype of breast cancer due to a low availability of therapeutic remedies. Recently, antibody-drug conjugates dramatically resolved the landscape for the treatment of triple-negative breast cancer. This review mainly focuses on the chemistry, structure, mechanism of action, and role of antibody-drug conjugates in triple-negative breast cancer. Datopotecan Deruxtecan (Dato-DXd) is a new-generation ADC showing encouraging results for TNBC. In this review, we have also emphasized TROP-2-directed Datopotamab deruxtecan ADCs to treat triple-negative breast cancer, its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, adverse events, and their ongoing clinical trials.

Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer in the world and its incidence and mortality are increasing year by year, frequently diagnosed at an advanced stage. Traditional treatments such as surgery, chemotherapy, and radiotherapy have limited efficacy, so new diagnostic and treatment strategies are urgently needed. Recent research has discovered that intratumoral microbiota significantly influences the development, progression, and metastasis of HCC by modulating inflammation, immune responses, and cellular signaling pathways. Intratumoral microbiota contributes to the pathologic process of HCC by influencing the tumor microenvironment and altering the function of immune system. This article reviews the mechanism of intratumoral microbiota in HCC and anticipates the future possibilities of intratumoral microbiota-based therapeutic strategies for HCC management. This emerging field provides fresh insights into early diagnosis and personalized approaches for HCC while holding substantial clinical application potential to improve patient outcomes and tailor interventions to individual tumor profiles.

Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around - 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer.

Surgical treatments are promising for the treatment of lymphedema. It is important for patients, healthcare providers, and lymphedema community to understand that surgical treatments currently are not a cure for lymphedema but have provided promising options for patients. Post-operative care for patients following surgical treatment of lymphedema is vital to optimize and sustain patient outcomes. This expert-consensus statement addresses current practice and research needs for standardized post-operative care, a core set of outcome measures, quality of care, and training of healthcare providers. Current research and clinical practice support non-surgical lymphedema therapy, also known as conservative therapy of lymphedema (e.g., compression therapy, or manual lymph drainage, or Complete Decongestive Therapy) as an essential part of post-operative care. Importantly, patient education should focus on patients' understanding that surgery is not a cure and the importance to adhere to post-operative care and life-long self-monitoring to sustain surgical results of limb volume reduction, relief of symptoms, and mitigate known or ongoing risk factors for recurrence of lymphedema. To optimize patient outcomes, it is crucial to have a multidisciplinary professional team consisting of well-qualified and credentialed healthcare providers participating in ongoing training and education. The essentials recommended by this expert-consensus are an initial and foundational step to build clinical standards for best practice and provide directions for future research.

Breast cancer-related lymphedema (BCRL) remains a challenging condition impacting function and quality of life. Complete decongestive therapy (CDT) is the current standard of care, necessitating a comprehensive review of its impact. This paper presents a systematic review (SR) of SRs on CDT's efficacy in BCRL, and the components of manual lymph drainage (MLD) and exercise. A literature search yielded 13 SRs published between January 2018 and March 2023 meeting inclusion criteria, with varied quality ratings based on the AMSTAR II. A sub-analysis of CDT investigated the within group effect size estimations on volume in different stages of lymphedema. While a moderate quality SR indicated support for CDT in volume reduction, other SRs on the topic were of critically low quality. Larger effect sizes for CDT were found for later stage BCRL. The impact of MLD as a component of CDT demonstrated no additional volume benefit in a mix of moderate to low quality SRs. Similarly, exercise's role in volume reduction in CDT was limited, although it demonstrated some benefit in pain and quality of life. A rapid review of trials published January 2021-March 2023 reinforced these findings. Variability in CDT delivery and outcomes remained. These findings underscore the need to standardize staging criteria and outcome measures in research and practice. Future research should focus on refining interventions, determining clinically important differences in outcomes, and standardizing measures to improve evidence-based BCRL management. Current evidence supports CDT's efficacy in BCRL. MLD and exercise as components of CDT have limited support for volume reduction.

Several recent studies have investigated the validity of precautionary practices for lymphedema risk reduction after breast cancer treatment, such as avoidance of blood pressure measurements, skin puncture, blood draws, and use of prophylactic compression during air travel. Other studies have elucidated risk factors for breast cancer-related lymphedema, such as axillary lymph node dissection and skin infection (cellulitis). Combining the current evidence base with the consensus opinion of lymphatic experts assembled at the American Cancer Society/Lymphology Association of North America Summit in October 2023, updated evidence-based risk reduction recommendations are presented for those with or at risk of breast cancer-related lymphedema. Recommendation topics include prospective surveillance, patient education, individual risk factors, exercise, blood pressure, skin care and hygiene, skin puncture and blood draws, surgical procedures, prophylactic compression, air travel, and hot climate and sauna. These recommendations will help inform education and medical choices for individuals treated for breast cancer who are at risk of or diagnosed with breast cancer-related lymphedema. More high-quality evidence is required to allow the development of risk reduction recommendations for other cancer types such as gynecological, melanoma, and head and neck. It is recommended that clinicians and organizations serving people at risk of or with lymphedema align risk reduction guidelines with the evidence-based recommendations provided within this consensus document and companion manuscripts from the American Cancer Society/Lymphology Association of North America Lymphedema Summit: Forward Momentum: Future Steps in Lymphedema Management.