Current Treatment Options in Oncology最新文献

Opinion statement: Breast cancer does not wait until a woman reaches her 50's to strike. One in six cases occurs in women between the ages of 40 and 49 and breast cancer is the most prevalent cancer and the leading cause of cancer-related deaths among women under 50 in the United States (10% of breast cancer deaths), emphasizing the urgency of early detection (American Society. 2024). Duffy et al. highlight the vital role of mammography screening in younger women, showing that starting screening at 40 reduces breast cancer mortality, with a consistent absolute reduction over time (Duffy et al. Health Technol Assess. 24(55):1-24, 2020). By starting yearly mammograms at 40, we could see a remarkable 40% reduction in breast cancer deaths (Monticciolo et al. J Am Coll Radiol. 18(9):1280-8, 2021). Screening at age 40 also adds little to the burden of overdiagnosis that already arises from screening at age 50 and older. Comparing this to biennial screening between ages 50-74, yearly screening at 40 saves approximately 13,770 more lives annually according to a report by the American Cancer Society published in JAMA in 2015 (Oeffinger et al. JAMA. 314(15):1599-614, 2015). But it's not just about saving lives; it's also about preserving quality of life. Between ages 40 and 49, 12-15% of years of life lost are attributed to breast cancer, highlighting the impact on women's lives. Early detection through screening can minimize these losses, ensuring more years spent with loved ones. It's clear: starting mammograms at age 40 saves lives. We must prioritize early detection and make screening accessible to all women, regardless of age. This proactive approach can reduce the burden of breast cancer and pave the way for a healthier future for women everywhere.

Opinion statement: Mutations in isocitrate dehydrogenase-1 (IDH1) are recurrent in several malignancies and prevalent in acute myeloid leukemia (AML). Olutasidenib and ivosidenib are inhibitors that target mutant IDH1 (mIDH1) and are FDA approved for the treatment of patients with mIDH1 AML. Olutasidenib and ivosidenib were identified through unique molecular screens and thus are structurally very different molecules. A difference in clinical outcomes has been observed with olutasidenib, which has a longer duration of response than ivosidenib, despite similar rates of response being achieved with the two drugs, such as complete remission (CR) or CR with partial hematologic recovery (CR/CRh). In the absence of a head-to-head trial, this review examines both the extent of differences in clinical outcomes with the two drugs and provides the first comparison of the unique molecular and mechanistic features of each drug, such as molecular structure and binding kinetics, that may contribute to the observed clinical difference in outcomes. Olutasidenib is structurally smaller with a lower molecular weight than ivosidenib (FW 355 vs FW 583) and thus occupies less space in the binding pocket of IDH1 dimers, making it resistant to displacement by IDH1 second-site mutations. In biochemical studies, olutasidenib selectively inhibits mutant but not wild-type IDH1, whereas ivosidenib appears to potently block both mutant and wild-type IDH1. Although they have the same target, olutasidenib and ivosidenib have unique molecular features, which may translate to selectivity differences in their inhibitory activity against IDH1.

Opinion statement: Rectal neuroendocrine neoplasms (NENs) are increasing in incidence. Most lesions are low grade, well-differentiated neuroendocrine tumours with good long term outcomes. However there is metastatic potential and resection offers the only option for a cure and in most cases should be offered to reduce the risk of metastases. Careful staging of rectal NENs should be performed prior to consideration of resection in order to ensure the appropriate technique is chosen, and reduce the risk of incomplete resection. Resection can be endoscopic or surgical, and selecting the appropriate resection technique relies on tumour characteristics such as size, grade, invasion into the muscularis propria, presence of lymph node involvement or of distal metastases. Some patients may require systemic therapies which may involve somatostatin analogues (SSAs), everolimus, tyrosine kinase inhibitors (TKIs), chemotherapy or peptide receptor radionuclide therapy (PRRT). Due the rarity of these tumours, much of the evidence is based on retrospective reviews or smaller cohort studies. This article is an update of the current evidence available to guide management.

Opinion statement: Osteosarcoma is the most common primary malignant bone tumor in adolescents and adults. The 5-year survival rate is 65% when localized; however, survival drops dramatically to 10-20% in cases of metastatic disease. Therapy for osteosarcoma saw its first significant advancement in the 1970-80's, with the introduction of our current standard of care, consisting of the neo/adjuvant treatment regimen methotrexate, doxorubicin (Adriamycin), and cisplatin (collectively referred to as MAP) and surgical resection. Since MAP, development of a better therapeutic approach has stalled, creating a plateau in patient outcomes that has persisted for 40 years. Despite substantial research into a variety of pathways for novel treatment options, clinical trials have not produced sizeable improvements in outcomes. In this article, we discuss our current neoadjuvant standard of care therapy, followed by a review of contemporary therapeutic options, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), monoclonal antibodies (mAbs), and chimeric antigen receptor (CAR) T cells. Lastly, we consider the challenges hindering the success of novel treatment options and future research directions.

Opinion statement: Lung cancer is expected to contribute to about 0.234 million new cases and about 0.125 million mortalities in the United States in the year 2024. Small cell lung cancer (SCLC), a neuroendocrine carcinoma, has lesser prevalence but is more aggressive at an extensive stage where the tumor is not only confined to hemithorax, mediastinum, and supraclavicular region but spread beyond the supraclavicular region. The prognosis of SCLC, irrespective of the limited or extensive stage, is very poor. Only a 5-10% overall survival rate in five years is expected and with extensive-stage SCLC, long-term disease-free survival is rare. In May 2024, the USFDA approved Tarlatamab-dlle, a DLL3 targeted bi-specific T-cell engager, for treating extensive-stage SCLC in adult patients, on or after platinum-based chemotherapy or on progression. Before the approval of Tarlatamab-dlle, only a few drugs, such as Atezolizumab and Durvalumab, received FDA approval for treating extensive-stage SCLC. It might be possible that Tarlatamab-dlle received accelerated FDA approval for extensive-stage SCLC, leaving some questions unanswered at this stage. This manuscript is focused on clinical, pre-clinical, and other pharmacological aspects of Tarlatamab-dlle for extensive-stage SCLC.

Opinion statement: Multiple myeloma (MM) is a heterogeneous plasma cell tumor with a survival period of several months to over ten years. Despite the development of various new drugs, MM is still incurable and recurs repeatedly. Bortezomib, a landmark event in the history of MM treatment, has dramatically improved the prognosis of patients with MM. Although proteasome inhibitors (PIs) represented by bortezomib, have greatly prolonged MM survival, unfortunately, almost all MM will develop bortezomib resistance, leading to relapse with a shorter survival. It has been reported that both the tumor microenvironment and myeloma cells drive bortezomib resistance. Multiple treatment methods have been attempted to overcome bortezomib resistance, but unfortunately, there has been no breakthrough. It is believed that the key resistance mechanism has not yet been discovered. A deeper understanding of the mechanism of bortezomib resistance and strategies to overcome it can help identify key resistance mechanisms and further improve the prognosis of MM.

Opinion statement: Bone metastasis, a frequent and detrimental complication of advanced cancers, often triggers bone deterioration events that severely compromise patient quality of life and prognosis. The past few years have witnessed the emergence and continuous advancements in immunotherapy, ushering in innovative therapeutic prospects for bone metastasis. These advancements include not only the use of immune checkpoint inhibitors (ICIs), both as standalone and combined treatments, but also the investigation of novel targets within immune cells residing in bone metastases. These breakthroughs have instilled fresh optimism for effectively managing patients with bone metastasis. This article endeavors to present an exhaustive review of the recent progress made across a spectrum of immunotherapeutic strategies and targeted therapies specifically designed for individuals battling bone metastasis from malignant tumors. By doing so, it seeks to offer insights that can inform clinical practices and guide further medical research in this domain.

Opinion statement: Gastrointestinal stromal tumor (GIST) is characterized by well-defined oncogenes. Despite the significant improvement in treatment outcomes with adjuvant imatinib therapy for patients, drug resistance remains a major challenge for GIST therapy. This review focuses on the mechanisms contributing to drug resistance phenotype in GIST, such as primary imatinib-resistant mutants, secondary mutations, non-covalent binding of TKI to its target, tumor heterogeneity, re-activation of pro-survival/proliferation pathways through non-KIT/PDGFRA kinases, and loss of therapeutic targets in wild-type GIST. Corresponding suggestions are proposed to overcome drug-resistance phenotype of GIST. This review also summarizes the suitability of currently approved TKIs on different KIT/PDGFRA mutations and updates related clinical trials. Recent potent drugs and emerging strategies against advanced GISTs in clinical trials are presented. Additionally, metabolic intervention offers a new avenue for clinical management in GIST. A landscape of metabolism in GIST and metabolic changes under imatinib treatment are summarized based on currently published data. The OXPHOS pathway is a promising therapeutic target in combination with TKI against sensitive KIT/PDGFRA mutants. Comprehensive understanding of the above resistance mechanisms, experimental drugs/strategies and metabolic changes is critical to implement the proper therapy strategy and improve the clinical therapy outcomes for GIST.

Opinion: All opioids have a risk of causing respiratory depression and reduced cerebral circulation. Fentanyl has the greatest risk of causing both. This is particularly a concern when combined with illicit opioids such as diamorphine (also known as heroin). Fentanyl should not be used as a frontline potent opioid due its significant risks. Buprenorphine, a schedule III opioid, morphine, or hydromorphone is preferred, followed by oxycodone, which has a significant risk of abuse relative to buprenorphine and morphine. Although all opioids were equally effective in producing analgesia, the relative safety of each opioid is no longer a secondary concern when prescribing. In the face of an international opioid epidemic, clinicians need to choose opioid analgesics safely, wisely, and carefully.

Opinion statement: Myxoid liposarcoma (MLS) is a rare subtype of soft tissue sarcoma that distinguishes itself from conventional subtypes through its propensity for extrapulmonary metastasis. The distinctive magnetic resonance imaging (MRI) characteristics of MLS render it an invaluable tool for identifying primary and secondary lesions. Pathologically, MLS is characterized by the FUS-DDIT3 gene fusion. Accurate diagnosis, facilitated by MRI and pathological assessment, is critical for prognostication and the formulation of appropriate treatment strategies. Surgery remains the cornerstone of local management for MLS. The combination of surgery and radiotherapy can significantly reduce the local recurrence rate in MLS, as it is highly sensitive to both radiotherapy and chemotherapy. Additionally, for high-risk MLS cases with a large tumor diameter, chemotherapy has been shown to improve survival. The comprehensive treatment approach for MLS demonstrates superior local recurrence rates and survival rates compared to most soft tissue sarcomas. Current research focuses on developing effective therapies for unresectable or advanced disease based on genomic and phenotypic characteristics as well as the immune-tumor microenvironment.