Current Treatment Options in Oncology最新文献

Opinion statement: Bruton's tyrosine kinase (BTK) inhibitors are transforming chronic lymphocytic leukemia (CLL) treatment. Given the availability of both covalent and non-covalent BTK inhibitors (BTKis) CLL treatment has become more nuanced. Here the mechanisms of action, efficacy, and resistance patterns associated with both inhibitor classes are reviewed to help create a framework for integrating covalent and non-covalent BTKis into CLL treatment algorithms. Our treatment algorithm based on the available data is as follows, in the frontline setting when oral therapy is preferred/chosen and indefinite therapy is not a deterrent, irrespective of DNA and IGVH mutational status, a second-generation covalent BTK inhibitor (cBTKi) is recommended. In the relapsed/refractory setting when oral therapy is preferred a second-generation cBTKi is preferred. For those suffering disease progression during second generation cBTK, it is recommended to change to an alternative cBTKi and for those exposed to greater than two lines of therapy, challenging to a non-covalent BTKi (ncBTKi) in the form of pirtobrutinib. At the time of disease progression on a BTKi, we recommend testing for resistance mutations. Data on combination therapy's role and time-limited BTKi use remain under active investigation.

Non-melanoma skin cancers (NMSCs), particularly basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common malignancies in the Caucasian population. While localized disease has a high cure rate, advanced cases pose therapeutic challenges. The introduction of immune checkpoint inhibitors (ICIs) has revolutionized treatment; however, resistance and contraindications necessitate alternative strategies. Epidermal growth factor receptor (EGFR) inhibition, particularly with cetuximab, has emerged as a potential therapeutic option in cSCC. This review evaluates the role of cetuximab in NMSC, focusing on clinical efficacy, safety, and emerging therapeutic strategies. A literature search was conducted using PubMed and clinical trial databases to identify relevant studies on cetuximab in advanced cSCC and BCC. The review discusses its use as monotherapy, in combination with radiotherapy or chemotherapy, and in the post-ICI setting. Despite the dominance of ICIs in advanced cSCC, cetuximab remains a valuable option, particularly for patients with ICI failure or contraindications. Its role as a radiosensitizer and its potential combination with immunotherapy warrant further investigation. Future studies should clarify optimal sequencing and combination strategies to improve patient outcomes.

Opinion statement: Cancer-related alopecia (CRA) presents a significant challenge for many patients undergoing cancer treatment, often affecting their psychological well-being and sense of identity. In my opinion, the optimal management of CRA requires a proactive, personalized approach that prioritizes both prevention and regrowth, while taking into account the type of cancer therapy, patient goals, and overall clinical context. For patients receiving chemotherapy, especially taxane- or anthracycline-based regimens, scalp cooling should be offered as a first-line preventative option whenever feasible. Its demonstrated effectiveness, particularly when appropriately sequenced with chemotherapy agents, makes it a valuable tool in preserving hair and quality of life. For patients with contraindications to scalp cooling or limited access to this intervention, early counseling and support around hair loss expectations and coping strategies remain critical. In terms of regrowth, topical minoxidil remains the most evidence-based pharmacologic option and should be recommended, especially for patients with endocrine therapy- or chemotherapy-induced alopecia. While oral minoxidil shows promise, it should be used with caution until more robust safety data are available in oncology settings. Spironolactone, tretinoin, prostaglandin analogs, and red light therapy may be considered in select cases, especially when standard options are insufficient, though patients should be counseled on the limitations of available evidence. Ultimately, a patient-centered, multidisciplinary approach is key to optimizing outcomes in CRA care.

Opinion statement: Melanoma is the most malignant skin tumor and exhibits extremely aggressive behavior with a high tendency to metastasize. Although the 5-year survival rate of early-stage patients (stage I-II) can reach over 90%, intermediate- and late-stage patients (stage III-IV) still face a high risk of recurrence and metastasis even after surgical resection. Moreover, these patients show low sensitivity to traditional therapies such as chemotherapy and radiotherapy. While immune checkpoint therapies (ICIs) represented by PD-1 inhibitors have significantly improved patient prognosis, they remain ineffective in 30%-40% of cases due to tumor immune escape or microenvironmental suppression. Additionally, long-term use of ICIs may induce autoimmune side effects (e.g., thyroid dysfunction). Therefore, there is an urgent need to develop more precise and durable treatment strategies. Vaccines for the treatment of melanoma represent one of the most promising therapeutic approaches. Melanoma vaccines activate the immune system through antigen recognition, leading to precise tumor killing. The vaccine also induces immune memory, demonstrates safety, and can be combined with immune checkpoint inhibitors to significantly enhance efficacy-making it a vital treatment for postoperative high-risk patients in their pursuit of long-term disease-free survival. With theoretical breakthroughs and technological iterations in immunotherapy, the development of melanoma vaccines has thrived and shown encouraging efficacy in clinical trials. Current mainstream melanoma vaccines are categorized into cell-based, peptide, nucleic acid, and viral types. Remaining challenges include complex and costly production processes, individual variability in therapeutic response, limited efficacy in advanced-stage patients, and potential autoimmune risks. Although melanoma vaccines face many shortcomings and challenges, these difficulties are being actively addressed through innovative strategies. For example, mRNA vaccine optimization involves improving stability and immunogenicity while shortening preparation cycles via enhanced lipid nanoparticle delivery and antigen design; novel vaccine platforms include nanovaccines and phage vaccines; combination therapy strategies entail combining vaccines with immune checkpoint inhibitors or targeted therapies; and using multi-omics analysis and AI to predict neoantigens, screen patients most likely to benefit, and develop efficacy monitoring markers to optimize treatment regimens. Although most melanoma vaccines are still under research, their emergence exemplifies the realization of individualized precision medicine and marks a milestone in the shift from "passive killing" to "active immunomodulation" in cancer treatment. This study provides an overview of recent research on melanoma vaccines to enable readers to grasp the latest advances in this field.

Opinion statement: Cutaneous adverse events (cAEs) are among the most common toxicities associated with modern cancer therapies, which are particularly heightened among immunotherapies and targeted agents. Despite being frequently immune-mediated, the majority of cAEs are mild to moderate and can be effectively managed without interruption of anticancer treatment. In immunotherapies-receiving patients, common phenotypes of cAEs include eczema-like, lichenoid, psoriasiform, vitiligo-like, and bullous eruptions. Targeted therapies including epidermal growth factor receptor inhibitors, BRAF inhibitors/MEK inhibitors, and phosphoinositide 3-kinase inhibitors are frequently associated with papulopustular eruptions, xerosis, paronychia, and photosensitivity. Mechanistically, cAEs may result from on-target immune activation, which correlates with treatment efficacy, or off-target hypersensitivity. Notably, certain phenotypes such as vitiligo, alopecia areata, and lichenoid reactions have been associated with improved survival in melanoma and non-small cell lung cancer. Management is guided based on the Common Terminology Criteria for Adverse Events grading, emphasizing the role of topical therapies for mild cases, systemic corticosteroids or immunosuppressants for moderate-to-severe reactions, and biologic or novel topical agents for steroid-refractory disease. By timely and appropriate intervention, most cAEs are manageable and may carry favorable prognostic significance. Early dermatologic collaboration is essential to reduce morbidity and ensure uninterrupted oncologic therapy.

Opinion statement: Extensive-stage small cell lung cancer (ES-SCLC) remains a challenging disease with a poor prognosis, despite recent advances in immunotherapy. The integration of thoracic radiotherapy (TRT) with chemoimmunotherapy has emerged as a promising strategy to improve treatment outcomes. However, the optimal role and timing of TRT in the first-line treatment of ES-SCLC in the immunotherapy era are still under investigation. Traditional approaches to TRT, based on high-dose regimens, have shown limited efficacy in overcoming the immunosuppressive tumor microenvironment (TME) characteristic of SCLC. The advent of low-dose radiotherapy (LDRT) offers a novel perspective by modulating the TME to enhance antitumor immunity. This review aims to re-evaluate the role of TRT, particularly LDRT, in the context of evolving immunotherapy strategies for ES-SCLC. By examining recent clinical trials and preclinical studies, we discuss the potential mechanisms through which LDRT can reshape the TME, promote immune activation, and improve the efficacy of immunotherapy. Additionally, we highlight the ongoing clinical trials that are essential for validating these approaches and determining the optimal treatment paradigms.

Opinion statement: Dyadic interventions are uniquely positioned not only to improve psychosocial outcomes for those with cancer, but also to improve caregiver and relationship outcomes. Although dyadic interventions have demonstrated efficacy in reducing distress and improving quality of life among individuals with cancer and caregivers in the general population, their applicability to minoritized populations, such as LGBTQ + individuals, remains understudied. Adapting dyadic interventions may be particularly important for LGBTQ+ cancer survivors and their caregivers given that they face higher rates of psychological distress than their heterosexual and cisgender counterparts. In the absence of interventions created for LGBTQ+ dyads facing cancer, we rely on adjacent literature: studies focused on dyadic interventions for a broader population of those affected by cancer, as well as those addressing LGBTQ+ individuals outside the context of cancer. Together, this literature illustrates an opportunity to address the psychological distress faced by LGBTQ+ individuals through dyadic approaches. Given the identified gap in the literature, however, there is a need for new research to explore how dyadic interventions can improve psychological well-being among LGBTQ+ people facing cancer.

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.