Current Treatment Options in Oncology最新文献

Opinion statement: Melanoma is a malignant tumor that originates from activated or genetically altered epidermal melanocytes, resulting from the interplay of genetic, somatic, and environmental factors. It is the fastest-growing malignancy among the Caucasian population and has a high mortality rate, second only to lung cancer. Current mainstream treatments have led to unavoidable drug resistance and toxic side effects despite improvements in efficacy and prognosis. Traditional Chinese Medicine is a significant component of complementary and alternative medicine, playing a vital role in cancer treatment. Natural compounds derived from Chinese herbal medicines offer notable advantages owing to their multimolecular, multitarget, and multipathway characteristics. These compounds exert anti-melanoma effects through various mechanisms, including antiproliferation, promotion of apoptosis, inhibition of metastasis, suppression of angiogenesis, modulation of autophagy, and enhancement of the immune response. Furthermore, combining natural compounds with mainstream antagonistic medicine not only enhances treatment efficacy but also significantly reverses multidrug resistance. This article discusses the specific mechanisms by which natural compounds combat melanoma and reviews the recent research advancements in this field. It also addresses the challenges faced in the widespread clinical application of these natural compounds in melanoma treatment and outlines the future directions for their development.

Opinion statement: Desmoplastic small round cell tumor (DSRCT) is an aggressive soft-tissue sarcoma driven by the EWSR1::WT1 fusion protein resulting from a chromosomal translocation between the EWSR1 (Ewing sarcoma breakpoint region 1) gene on chromosome 22 and the WT1 (Wilms tumor 1) gene on chromosome 11. This disease typically occurs in post-pubertal adolescent and young adult males, which suggests it may be hormonally driven through the androgen receptor (AR) pathway. Over the years, various groups have established a relationship between AR and DSRCT. Profiling studies have noted a high expression of AR in DSRCT. Fine et al. showed that combined androgen blockade led to a clinical benefit in three (all male) of six patients with stable disease or at least a minor response lasting three months. The AR pathway is relevant not only in prostate cancer but has been discovered to be oncogenic in salivary gland cancers, melanoma, and breast cancer. Though numerous AR-directed therapies are available to treat prostate cancer, AR has not been extensively evaluated as a therapeutic target in DSRCT. Preclinical studies revealed that AR stimulation increased cell proliferation. Conversely, single-agent targeting of the pathway delayed tumor growth in xenograft models. Pharmacodynamic analysis showed that AR inhibition activates the PI3K/Akt/mTOR pathway, and recent epigenetic analysis of AR binding showed that it may interact with EWSR1::WT1 and the forkhead protein family of transcription factors that regulate development and cellular differentiation. A deeper understanding of the impact of AR on the epigenetic landscape and signaling pathway crosstalk of DSRCT promises to expand the therapeutic arsenal of agents available to combat this deadly disease.

Opinion statement: Ocular cancers, though rare, present significant therapeutic challenges due to their aggressive nature, high metastatic potential and anatomical constraints that limit drug delivery. Conventional therapies, including radiation, enucleation, and chemotherapy, often result in significant side effects and suboptimal outcomes. Recent advancements in nanomedicine offer promising alternatives, utilizing NPs for targeted drug delivery, gene therapy, photodynamic therapy, and brachytherapy. Nanocarriers such as liposomes, polymeric NPs, and lipid-based NPs improve drug bioavailability, reduce systemic toxicity, and enhance treatment efficacy. Additionally, gold and silver NPs serve as effective radiosensitizers, optimizing radiation therapy. Preclinical and clinical studies indicate the potential of nanomedicine-based approaches to revolutionize ocular cancer treatment. However, challenges remain, including optimizing nanoparticle formulations and addressing regulatory hurdles. This review underscores the transformative role of nanotechnology in major and deadly ocular cancers mainly Uveal Melanoma and Retinoblasoma and emphasized cutting-edge drug delivery systems poised to improve therapeutic precision, minimize side effects, and improve patient survival and quality of life.

Opinion statement: Sarcomas are a diverse group of rare, mesenchymal tumors that vary in terms of clinical behavior, aggressiveness, and responsiveness to treatment. The management of metastatic sarcoma is challenging and requires a multidisciplinary approach. Apart from a few subtypes of sarcomas that respond to targeted therapies, the vast majority of metastatic sarcomas are treated with chemotherapy regimens that have been unchanged for decades. These regimens are aggressive and cause clinically relevant toxicity. Despite this, treatment outcomes remain unsatisfactory and prognosis dismal. Metastatic disease is largely incurable, and new strategies are needed to simultaneously control metastatic disease while preserving patients' quality of life. For example, the optimal duration of palliative treatment for patients with metastatic sarcoma is unknown, as is the role and feasibility of planned treatment holidays. Whereas the benefit to patient quality of life from a treatment break can be easily predicted, it is not well understood the influence these treatment "holidays" have on overall survival (OS). Herein, we summarize the available literature on drug holidays in sarcoma and offer clinicians updated guidance for managing patients with metastatic disease.

Opinion statement: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enabling the immune system to effectively target and destroy cancer cells. While ICIs offer significant survival benefits across various malignancies, their use is associated with a unique profile of immune-related adverse events, including potentially fatal cardiovascular toxicities. Recent studies have highlighted various cardiac complications associated with ICIs, such as myocarditis, arrhythmias, heart failure, pericarditis, atherosclerosis, and hypertension. These complications arise from mechanisms involving T-cell activation and cytokine release. Patient-related factors such as pre-existing cardiovascular disease, diabetes mellitus, age, gender, and genetic predisposition, along with treatment-related factors like specific ICI regimens, contribute to these toxicities. To manage these complications effectively, comprehensive cardiovascular risk assessment and monitoring before, during, and after ICI therapy are crucial. Adhering to guidelines from the European Society of Cardiology (ESC) and other international organizations allows for early recognition of cardiovascular toxicities and tailored interventions. This review emphasizes the importance of cardioprotective measures, regular monitoring, and multidisciplinary collaboration between oncologists and cardiologists to mitigate cardiovascular risk and optimize patient outcomes. Ongoing research is essential to better understand the mechanisms of ICI-induced cardiovascular toxicities and to develop effective management strategies for affected patients. As we continue to expand the use of ICIs in oncology, balancing oncologic efficacy with cardiovascular safety remains critical.

Opinion statement: Vismodegib is a hedgehog inhibitor used in the treatment of basal cell carcinomas and basal cell nevus syndrome. However, treatment is associated with significant side effects that can impact compliance, including fatigue, muscle cramps, hair loss, and taste disturbance. Multiple strategies to change dosing frequency have been implemented to improve the tolerability. Vismodegib may be administered with non-daily dosing or with drug holidays to improve the side effects associated with administration. Intermittent dosing of vismodegib may be more appropriate for patients with locally advanced BCC and drug holidays may be more suited for patients with basal cell nevus syndrome. The most appropriate strategy in each case though will ultimately depend on patient preference.

Opinion statement: Ovarian Cancer (OC) is a serious health problem that affects a great number of women globally. It is still one of the deadliest gynecological cancers due to restricted treatment choices and late-stage diagnosis. Worldwide, OC ranks as the seventh most commonly diagnosed kind of malignant neoplasm in women and the eighth leading cause of death in them. Because of several reasons such as genetic and economic ones, the epidemiology of OC shows disparities between races and countries. Lack of public screening program makes it difficult to diagnose this cancer earlier and as a result, most OCs are detected after they have progressed to other parts. However, advances in biotechnology and artificial intelligence (AI) are transforming both early detection and treatment strategies. Over the years, the application of AI in OC screening has shown promising results. The best way to get the drawbacks of traditional treatment methods is to combine newly developed strategies with existing treatment choices. Additionally, clinical researches are crucial to ensure the practical implementation of these advancements in healthcare settings. Utilizing state-of-the-art technologies and creative strategies will offer significant opportunity to lessen the worldwide impact of this curable cancer thereby enhancing women's quality of life in low and middle income countries (LMICs) and beyond. Hence, this review explores recent breakthroughs in ovarian cancer screening and therapy, highlighting the synergistic role of biotechnology and AI in improving patient outcomes that reshapes the ovarian cancer treatment landscape.

Opinion statement: At initial diagnosis, over half of the patients with metastatic colorectal cancer (mCRC) are aged 65 years or older. In this population, age-related declines in organ reserve and the presence of comorbidities can significantly weaken drug tolerance and affect treatment outcomes. However, existing clinical guidelines, largely based on clinical trials involving younger, fitter adults, may not be fully applicable to older patients, particularly those are vulnerable. Moreover, chronologic age and commonly used performance assessment tools, such as the Eastern Cooperative Oncology Group and Karnofsky Performance Status scores, are insufficient for accurate evaluation of physiological fitness in older adults. To provide evidence-based references for clinicians, this review summarizes advances in targeted therapy and immunotherapy for elderly patients with mCRC over the past five years, with a focus on vascular endothelial growth factor (VEGF) targeting agents, epidermal growth factor receptor (EGFR) inhibitors, multi-targeted tyrosine kinase inhibitors (TKIs) and single-agent immunotherapy. Overall, for elderly patients assessed as fit, first-line treatment may include dose-reduced doublet chemotherapy combined with VEGF targeting agents, or alternatively, single-agent chemotherapy plus VEGF targeting agents. For vulnerable elderly patients with mCRC, single-agent chemotherapy with VEGF targeting agents remains the preferred first-line strategy, while RAS wild-type left-sided tumors may benefit from single-agent chemotherapy plus EGFR inhibitors. Although multi-targeted TKIs have shown positive outcomes in elderly patients who are intolerant to other therapies. There is currently no evidence supporting their use in first-line treatment or combination therapy. In terms of immunotherapy, similar to the general mCRC population, single-agent immunotherapy is recommended as a first-line option for elderly microsatellite instability-high/mismatch repair-deficient patients. Notably, integrating comprehensive geriatric assessment into clinical practice can facilitate personalized treatment strategies, particularly for vulnerable and frail patients.

Opinion statement: Diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) is the most common aggressive lymphoma and can be cured with CHOP-R immunochemotherapy in 60% of cases. The second-line therapy includes salvage regimens followed by autologous stem cell transplantation (ASCT), which offers a cure to a minority of patients due to limitations in efficacy and eligibility. These data present the unmet need in the field, and this review article focuses on how second-generation chimeric antigen receptor T (CAR T) cell therapy targeting CD19 antigen may improve the outcomes with relapsed/refractory DLBCL. In heavily pretreated patients, who have dismal outcomes with conventional therapy, all three approved products-tisangenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), and lisocabtagene maraleucel (liso-cel) have shown durable, unprecedented complete responses with the potential for cure. When compared to salvage regimens and ASCT as the standard of care, axi-cel and liso-cel, unlike tisa-cel, have demonstrated superiority in long-term control. In ASCT-ineligible r/r DLBCL, liso-cel has shown a favourable benefit-risk ratio. Regarding safety, two adverse events of interest have emerged: cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both of which are manageable. Real-world evidence reflects the results of pivotal trials while favouring axi-cel in heavily pretreated patients, albeit with higher toxicity. The main barrier to the implementation of this treatment modality is the cost associated with the process of CAR T therapy, along with complications and reimbursement issues. However, the barriers can be overcome, and CAR T therapy has the potential to become the standard of care in relapsed/refractory DLBCL. Furthermore, with advances in the scientific engineering of CAR products and the understanding of novel treatment modalities currently being tested in clinical trials, we believe that targeted cellular therapy will become the future of relapsed/refractory DLBCL treatment.