Current Oncology Reports最新文献

Purpose of the review: This review aims to explore the pivotal role of long non-coding RNAs (lncRNAs) as epigenetic regulators in the pathogenesis of multiple myeloma (MM). Additionally, we have portrayed the dual role of lncRNAs in the epigenetic landscape of MM pathobiology.

Recent findings: In MM, lncRNAs are pivotal for proliferation, progression, and drug resistance by acting as miRNA sponges, regulating mRNA activity through microRNA recognition elements (MREs). Epigenetic modifications in lncRNAs influence gene expression, with some like MEG3, GAS5, CRNDE, and H19 showing promoter hypermethylation, while MALAT1 exhibits hypomethylation. Targeting lncRNAs using siRNA, ASO, CRISPR-Cas9, or small molecule inhibitors shows promise in preclinical studies, alongside the potential benefits of epigenetic-based therapies such as DNMTi and HDACi. Clinical trials combining epigenetic modifiers with standard chemotherapy show encouraging results, especially in relapsed/refractory MM. The key finding of the studies highlighted in the review paves the way for understanding the epigenetic role of lncRNAs in MM disease progression and biology. In addition, the novel therapeutic strategies that have shown promising results have been highlighted. The adoption of the epigenetic landscape into therapeutics in addition to existing treatment strategies may increase the efficacy of treatment approaches.

Purpose of review: The advent of checkpoint immunotherapy has dramatically changed the outcomes for patients with cancer. However, a considerable number of patients have little or no response to therapy. We review recent findings on the connection between the gut microbiota and the immune system, exploring whether this link could enhance the effectiveness of immunotherapy.

Recent findings: Clinical studies have reported specific types of bacteria in larger quantities at baseline in responders than in non-responders, especially Akkermansia mucinifila, Ruminococcaceae, Faecalibacterium, and Lachnospiraceae. Following the consumption of a high-fiber diet, bacteria in the gut ferment dietary fiber to short-chain fatty acids (SCFAs), like acetate, propionate, and butyrate. Some of the SCFAs nurture intestinal epithelial cells, and some enter the bloodstream. Here SCFAs can activate DC8 + cytotoxic T-cells to induce cancer cell death. High fiber intake in the diet was associated with a reduced risk of progression or death during checkpoint immunotherapy. Recent findings demonstrate that high-fiber plant-based diets such as the Mediterranean Diet positively influence the gut microbiota whereas antibiotics and proton pump inhibitors can negatively influence outcomes of cancer immunotherapy by changing the gut microbiota. This narrative review provides evidence of an association between types of bacteria and their metabolites and favorable responses to checkpoint immunotherapy. Prospective clinical trials are needed to determine if diet interventions can improve treatment outcomes.

Purpose of review: Human epidermal growth factor receptor 2 (HER2) is a critical target in advanced gastric cancer (AGC). This review highlights the current treatment landscape, lessons learned from past clinical trials, and prospects for future treatment strategies for HER2-positive AGC.

Recent findings: Trastuzumab had been the standard treatment for HER2-positive AGC for a decade, and subsequently, trastuzumab deruxtecan, an antibody-drug conjugate (ADC), emerged with an impressive response. Recently, the addition of pembrolizumab to first-line chemotherapy plus trastuzumab has become a novel standard treatment. Past clinical trials of HER2-targeted therapies, which succeeded in HER2-positive breast cancer but failed in AGC, have deepened our understanding of resistance mechanisms. Based on these results, several clinical trials of novel HER2-targeted therapies, including immunologic approaches such as CAR-T cells and vaccines, are currently ongoing. Circulating tumor DNA is also expected to be a tool for real-time biomarker analysis. Additionally, ADCs with a bystander effect have the potential to expand the scope of HER2-targeted therapies to HER2-expressing, including HER2-low AGC. Learning from past trials, further development of novel HER2-targeted therapies is underway, expanding their scope to HER2-expressing AGC. Meanwhile, selecting optimal treatment is a challenging issue in cases with HER2-low AGC overlapping with other biomarkers like CLDN18.2.

Purpose of review: The purpose of this review is to outline the current knowledge on epidemiology, diagnosis and management of neuroendocrine neoplasms (NENs) that develop in the context of Von Hippel-Lindau (VHL) syndrome.

Recent findings: Pancreatic NENs develop in 8-17% of VHL patients (vPNENs) and are mostly multi-focal, cystic and non-functioning. Surgical resection is recommended for vPNENS > 3 cm that exhibit higher metastatic potential or in tumors with short doubling time while in the 20% of cases with metastatic disease the HIF-2 A inhibitor belzutifan is considered a promising option. Pheochromocytomas arising in VHL type 2 are often bilateral and have a noradrenergic phenotype while they are associated with increased risk of recurrence. High-specific activity [¹³¹I]-MIBG and sunitinib are the treatment options with the highest level of evidence whereas studies on belzutifan are evolving. Life-long surveillance and management in the context of a multidisciplinary team are suggested to achieve the best clinical outcome.

Purpose of review: In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.

Recent findings: Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures. In this new frontier, translational efforts are underway to personalize the use of ADCs, including refining HER2 quantification and elucidating genetic, epigenetic, and post-translational mechanisms of resistance. ADCs have provided important treatment options for patients with breast cancer. As patients become eligible for more than one ADC, there is an unmet need to identify the appropriate timing and sequence of these therapies to maximize their efficacy.

Purpose of review: There has been controversy in the management of gastroesophageal (GE) junction cancers with pre-operative chemoradiation and peri-operative chemotherapy as accepted practices. We aim to assess and compare the defining trials establishing current standards of care and discuss future directions seeking to further improve patient-centered outcomes in GE junction cancers.

Recent findings: Over the last two decades, several large Phase III randomized trials have been conducted including GE junction cancers, showing superiority of 1) pre-operative chemoradiation over surgery (CROSS) and 2) peri-operative chemotherapy with FLOT over CROSS without radiotherapy (FLOT 4). While NEO-Aegis suggested equipoise between the CROSS vs. peri-operative chemotherapy, the recently presented ESOPEC trial demonstrated superiority of peri-operative FLOT versus CROSS in esophagus and GE junction adenocarcinomas. Based on the ESOPEC trial, peri-operative chemotherapy with FLOT appears to be a preferred regimen for patients with resectable GE junction adenocarcinomas in patients able to receive FLOT. There is evidence in support of other practices, such as induction chemotherapy, pre-operative chemoradiation, definitive chemoradiation for those not fitting ESOPEC criteria. Chemoradiation ± chemotherapy with non-operative intent represents a promising strategy for patients seeking organ preservation, and ongoing studies will better define its feasibility and long-term outcomes.

Purpose of review: This review examines contemporary strategies for managing brain metastases (BM) from common cancers such as lung, breast, and melanoma. We evaluate the efficacy and applicability of targeted therapies and immunotherapies, exploring their potential to cross the blood-brain barrier and improve patient outcomes.

Recent findings: Recent studies have shown that tyrosine kinase inhibitors, immune checkpoint inhibitors, and ADCs effectively treat BM. These treatments can overcome the challenges posed by the blood-brain barrier and improve therapeutic outcomes. ADCs are promising because they can deliver cytotoxic agents directly to tumor cells, which reduces systemic toxicity and increases drug delivery efficiency to the brain. Personalized medicine is becoming increasingly significant in treatment decisions, with biomarkers playing an essential role. Advances in molecular genetics and drug development have led to more refined treatments, emphasizing the precision medicine framework. The management of BM is evolving, driven by drug efficacy, resistance mechanisms, and the need for personalized medicine. Integrating ADCs into treatment regimens represents a significant advancement in targeting metastatic brain tumors. Despite these advances, BM management still presents considerable challenges, requiring ongoing research and multi-institutional trials to optimize therapeutic strategies. This review outlines the current state and future directions in treating BM, highlighting the critical need for continued innovation and comprehensive clinical evaluations to improve survival rates and quality of life for affected patients.

Purpose of review: Adolescent and young adult (AYA) breast cancer survivors face a significant risk of infertility due to the gonadotoxic effects of (neo)adjuvant therapy, which complicates their ability to conceive post-treatment. While (neo)adjuvant therapy primarily aims to improve recurrence-free and overall survival, fertility preservation strategies should also be considered for young patients. This narrative review explores recent advancements in fertility preservation techniques, such as oocyte, embryo, and ovarian tissue cryopreservation, and evaluates the feasibility of modifying breast cancer (neo)adjuvant therapy to preserve fertility without compromising survival outcomes.

Recent findings: Our review highlights that clinical trials with co-primary endpoints of oncological safety and fertility preservation are limited, and substituting standard treatment regimens solely for fertility preservation is currently not recommended. Nevertheless, new clinical studies have emerged that either exclude highly ovarian-toxic agents, such as cyclophosphamide, or omit adjuvant therapy altogether, even if fertility preservation is not their primary endpoint. Unfortunately, many of these trials have not evaluated ovarian toxicity. Notably, since 2020, major oncology organizations, including the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO) have advocated for the routine assessment of ovarian toxicity in all clinical trials. The review underscores the importance of incorporating ovarian toxicity as a standard endpoint in future trials involving premenopausal breast cancer patients to identify treatment regimens that can effectively balance fertility preservation with treatment efficacy.

Purpose of review: The purpose of this review is to provide an overview of the practical applications of comprehensive cancer rehabilitation services through telemedicine.

Recent findings: Telemedicine has been shown to be an effective platform leading to positive outcomes and high patient/provider satisfaction for several forms of skilled therapy and cancer physiatry visits. Several survivorship resources are also available through telemedicine in recent years. Telemedicine can increase accessibility to geographically sequestered services including cancer physiatry, skilled therapy and survivorship resources. In certain situations and for specific services, telemedicine can be effective, however, in other situations such as the evaluation of new neurologic deficits or when providing manual therapies, in-person visits should take precedence.

Purpose of review: At present, breast cancer represents the most common malignancy diagnosed in women worldwide. Due to the trend toward delayed childbearing, many women of reproductive age are being diagnosed with breast cancer and treated with chemotherapy or hormone therapy which can adversely affect their fertility. This literature review discusses the effects of breast cancer treatment on fertility and options for fertility preservation.

Recent findings: Treatments used in the management of breast cancer often result in a diminished ovarian reserve, premature ovarian insufficiency, and treatment-related amenorrhea. Chemotherapy may cause direct damage to oocytes and deplete ovarian reserve, while hormone therapies such as tamoxifen can cause amenorrhea and delay childbearing. Targeted therapies and radiotherapy may also pose risks to reproductive health. Fertility preservation is a concern for patients, and many of them may refuse or prematurely discontinue treatment to preserve their fertility. It is relevant to incorporate considerations of fertility at the time of treatment planning for breast cancers and to provide information to appropriate patients regarding their options. Current techniques available for fertility preservation include ovarian suppression, oocyte and embryo cryopreservation, and ovarian tissue cryopreservation. In spite of these techniques being in existence, there are plenty of barriers that deter the patients from availing them, including lack of awareness, financial constraints, and the need for timely treatment. This review implicates that these challenges require multidisciplinary approaches and a patient-centered approach. Further research is warranted toward the improvement of fertility preservation techniques, individual variability in protocols, and newer advances in reproductive medicine to further optimize quality of life in survivors of breast cancer.