Cancer treatment reviews最新文献

Background

Primary and acquired endocrine resistance remains a major issue in the treatment of hormone receptor positive breast cancer. Acquired resistance often results from estrogen receptor 1 (ESR1) mutations leading to estrogen independent estrogen receptor activation. Selective estrogen receptor degraders (SERDs) induce degradation of this receptor, thereby overcoming this resistance. The intramuscular administration and modest efficacy of fulvestrant, the first SERD, triggered development of oral, more potent SERDs. This narrative review gives an overview of the current evidence regarding this new drug class.

Methods

Medline/PubMed and Embase database were screened using a systematic search strategy. We assessed the San Antonio Breast Cancer Symposium abstract reports, the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meeting resources by applying the following terms: ‘SERD’, ‘giredestrant’, ‘elacestrant’, ‘imlunestrant’, ‘amcenestrant’, ‘camizestrant’ and ‘rintodestrant’. ClinicalTrials.gov was consulted to include ongoing trials.

Results

The search retrieved 1191 articles. After screening, 108 articles were retained. In the phase 3 EMERALD trial, elacestrant demonstrated benefit in progression free survival (PFS) in second line metastatic disease in postmenopausal women or men, leading to Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the ESR1 mutated population. This PFS advantage was more pronounced among patients who had priorly received at least 12 months of a cyclin-dependent kinases 4/6 inhibitor (CDK4/6i). In the phase 2 SERENA-2 trial, camizestrant improved PFS as second line treatment. However, trials of giredestrant and amcenestrant failed to show PFS benefit in second line metastatic setting. In the preoperative setting, several oral SERDs resulted in a significant reduction of tumoral proliferation. Furthermore, many trials are still in progress.

Conclusion

Oral SERDs constitute an exciting new drug class. Ongoing and future research will further refine the role of these drugs next to standard endocrine treatments and targeted therapies.

With the advancements in conventional treatment modalities such as radiation, chemotherapy, and surgery, as well as the emergence of immunotherapy, the overall cure rate for solid tumor malignancies has experienced a significant increase. However, it is unfortunate that exposure to cancer treatments can have detrimental effects on the function of osteoblasts and osteoclasts, disturbing bone metabolic homeostasis in patients, as well as causing damage to bone marrow cells and other bone tissues. Consequently, certain tumor treatment options may pose a risk for subsequent bone diseases. Common bone disorders associated with cancer treatment include osteonecrosis, bone loss, and secondary bone tumors. (1)Cancer treatment-related osteonecrosis is primarily linked to the use of radiation therapy and certain chemicals, such as bisphosphonates, denosumab, antiangiogenic agents, and immunomodulators. It has been observed that high-dose radiation therapy is more likely to result in osteonecrosis. (2)Chemicals and hormones, particularly sex hormones, glucocorticoids, and thyroid hormones or thyrotropic hormones, are among the factors that can contribute to cancer treatment-related bone loss. (3)Secondary bone tumors differ from metastases originating from primary tumors, and radiotherapy plays a significant role in their development, while chemotherapy may also exert some influence. Radiogenic secondary bone tumors are predominantly malignant, with osteosarcoma being the most common type. Chemotherapy may be a risk factor for the relatively rare occurrence of secondary Ewing sarcoma of the bone. These treatment-related bone disorders have a considerable adverse impact on the prognosis of cancer patients. Hence, it is imperative to prioritize the bone health of patients undergoing cancer treatment and give it further attention.

Background

Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro.

Methods

PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test.

Findings

A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC₀₂₅: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC₀₂₅: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration.

Interpretation

Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.

Human epidermal growth factor receptor-2 (HER2) is overexpressed in various solid tumor types, acting as an established therapeutic target. Over the last three decades, the fast-paced development of diverse HER2-targeted agents, notably marked by the introduction of the antibody-drug conjugate (ADC), yielding substantial improvements in survival rates. However, resistance to anti-HER2 treatments continues to pose formidable challenges. The complex structure and dynamic dimerization properties of HER2 create significant hurdles in the development of novel targeted therapeutics. In this review, we synthesize the latest insights into the structural intricacies of HER2 and present an unprecedented overview of the epitope characteristics of HER2-targeted antibodies and their derivatives. Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future.

The t(11;14) translocation is among the most prevalent cytogenetic abnormalities in multiple myeloma (MM), distinguished by its unique features and biology that have been thoroughly explored for decades. What further sets this MM subtype apart is its oscillating prognostic significance, from initially being considered a favorable alteration to intermediate risk and potential future reclassification as favorable risk. Despite not being inherently a high-risk alteration indicative of an aggressive phenotype, it appears that t(11;14)-MM is less responsive to novel agents like proteasome inhibitors and immunomodulatory drugs which have otherwise transformed the disease’s treatment landscape, perhaps partially explained by its reduced propensity for immunoglobulin production and oligosecretory nature. However, its distinct reliance on Bcl-2 has heightened its sensitivity to venetoclax. Further subclassification based on morphological and genomic characteristics could enhance our prediction models of treatment responses and enable more tailored therapeutic strategies for patients. This review aims to encapsulate the existing research evidence in this area.

The aim of this review is to provide an overview of the status of patient/public involvement (PPI) in oncology research, including definitions, regulatory aspects, ongoing clinical activities in different countries, achievements and difficulties. The 10-year activities of the Swiss Group for Clinical Cancer Research (SAKK) Patient Advisory Board are described, illustrating challenges faced and solutions in daily practice.

Even though clinical data are still limited, it appears PPI has great potential for development in oncology. The drive for precision medicine, activities of patient organizations, pharmaceutical industry interest, and strong support from regulatory agencies, are facilitators to integration of PPI throughout the drug development process. Despite the availability of guidance documents providing recommendations for the implementation of PPI, lack of human and structural resources, training for patients / caregivers and healthcare personnel, and lack of collaboration among stakeholders are some of the main barriers reported. More rigorous reporting of PPI in clinical studies is needed, including the methods to evaluate the impact of PPI and in the representation of patients as partner.

Colorectal cancer that occurs before age of 50 is defined as Early-Onset Colorectal Cancer (EOCRC). Its incidence has worryingly increased since the late 90 s and is expected to keep rising in the next future, despite Late-Onset CRC (LOCRC) is decreasing worldwide. Because of this, there is an urgent need to better understand this subset of patients in order to give them the best treatment possible. However, most of the literature is retrospective and often discordant. In this review, we aim to provide a general overview of the issue, endeavoring to highlight the current available knowledge. We decided to move from the beginning, investigating risk factors and inheritance, passing through diagnosis and clinical aspects, and to conclude with the translational part, focusing on the biology of the tumor. However, lot of questions remain open, including screening age and prognosis. Indeed, young patients tend to be treated more aggressively, even if a survival benefit has not been proven yet. Every clinician should be aware of the best practice for young people, and more translational studies are awaited in order to clarify is EOCRC represents a distinct biological entity.

Defined as scarce expression of hormone receptors and human epidermal growth factor receptor 2, triple-negative breast cancer (TNBC) is labeled as the most heterogeneous subtype of breast cancer with poorest prognosis. Despite rapid advancements in precise subtyping and tailored therapeutics, the ensuing cancer therapy-related cardiovascular toxicity (CTR-CVT) could exert detrimental impacts to TNBC survivors. Nowadays, this interdisciplinary issue is incrementally concerned by cardiologists, oncologists and other pertinent experts, propelling cardio-oncology as a booming field focusing on the whole-course management of cancer patients with potential cardiovascular threats. Here in this review, we initially profile the evolving molecular subtyping and therapeutic landscape of TNBC. Further, we introduce various monitoring approaches of CTR-CVT. In the main body, we elaborate on typical cardiotoxicities ensuing anti-TNBC treatments in detail, ranging from chemotherapy (especially anthracyclines), surgery, anesthetics, radiotherapy to immunotherapy, with future perspectives on promising directions in the era of artificial intelligence and traditional Chinese medicine.