Current Opinion in Oncology最新文献

Purpose of review: New evidence has recently emerged regarding the utility and benefits of dual p16 INKa (p16) and Human papillomavirus (HPV) status testing when determining the diagnosis and prognosis of patients with oropharyngeal cancer.

Recent findings: HPV RNA polymerase chain reaction (PCR) is the most accurate diagnostic test. The other assays (HPV DNA PCR, HPV DNA/RNA in-situ hybridization (ISH) and p16) applied to formalin fixed tumour tissue have varying but high sensitivities and specificities. Dual p16 and HPV testing identifies discordant (p16+/HPV- or p16-/HPV+) results in 9.2% of cases, who have significantly poorer prognoses than p16+/HPV+, particularly in smokers. The proportion of discordant cases varies by region, and appears to be highest in regions with lowest attributable (p16+/HPV+) fractions. Dual testing improves prognostication for oropharyngeal cancer cases by identifying discordant cases and improving the prognostic power of the Tumour Node Metastasis (TNM) classification, especially in regions with high discordant rates.

Summary: Dual testing is essential when considering patients for clinical trials of treatment de-escalation, and may be important when counselling patients on prognosis, especially in regions with high discordant rates and in smokers.

Purpose of review: The evolving role of stereotactic ablative radiation therapy (SABR) as metastasis-directed therapy (MDT) for oligometastatic prostate cancer (omPCa) will be discussed.

Recent findings: Oligometastatic disease (OMD) is an intermediate state between localized and wide-spread malignant disease. OMD has recently been spotlighted given the increasing demonstration of clinical benefit from local therapies despite presence of metastatic disease and allure of the curative potential of MDT in select cases. Among the different forms of MDT, SABR has rapidly become a widely adopted treatment modality. Significant efforts in this space have focused on omPCa, owing to its relatively indolent biology, presence of a sensitive and specific serum biomarker and recent advances in molecular imaging. While most studies have evaluated the role of SABR MDT in hormone sensitive omPCa, new emerging clinical data also suggests benefits of SABR MDT for even castration-resistant disease.

Summary: Treating omPCa with SABR MDT appears to generate an efficacy signal with minimal morbidity across both hormone-sensitive and castration-resistant disease. However, additional definitive omPCa trial data are needed. Future research efforts should investigate biomarkers for this heterogeneous disease space and the role of SABR MDT in combination with systemic agents to improve upon standard of care treatments.

Purpose of review: In this review, we summarized published articles on the role of tripartite motif (TRIM) family members in the initiation and development of human malignancies.

Recent findings: The ubiquitin-proteasome system (UP-S) plays a critical role in cellular activities, and UP-S dysregulation contributes to tumorigenesis. One of the key regulators of the UP-S is the tripartite motif TRIM protein family, most of which are active E3 ubiquitin ligases. TRIM proteins are critical for the biological functions of cancer cells, including migration, invasion, metastasis, and therapy resistance. Therefore, it is important to understand how TRIM proteins function at the molecular level in cancer cells.

Summary: We provide a comprehensive and up-to-date overview about the role TRIMs play in cancer progression and therapy resistance. We propose TRIM family members as potential new markers and targets to overcome therapy failure.

Purpose of review: The aim of this review is to outline the current landscape of advanced melanoma treatment options, provide insights on selecting combination therapies within different clinical scenarios, capture clinical relevance of anti-programmed cell death protein 1 (PD-1) monotherapy, and explore the unmet needs with immune check-point inhibitors (ICI) in advanced melanoma.

Recent findings: ICI based treatment consisted of single agent ICI or dual combination ICI-ICI is the standard of care of front-line treatment of metastatic or unresectable melanoma. PD-1 inhibitors (Pembrolizumab and Nivolumab) improved progression free survival (PFS) and overall survival (OS) compared to chemotherapy and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors (Ipilimumab and Tremelimumab). The dual ICI combination (Nivolumab and Ipilimumab) provided profound and durable responses better than monotherapy, and the longest overall survival ever achieved in advanced disease, including in patients with murine sarcoma viral oncogene homolog B (BRAF)-mutated disease, but at the cost of a high risk of severe toxicity. The new dual blockage of LAG-3 and PD-1 (Nivolumab-Relatlimab) emerges as a valid option with promising efficacy outcomes and a favourable toxicity profile. Mature survival data is still needed to capture the real benefit.

Summary: These new plethora of options pose new challenges not only for optimal treatment sequencing strategies but especially for management of adverse effects, endorsing the need to integrate a holistic and personalized approach for patient care.

Purpose of review: Cellular dormancy is a major contributor to cancer progression and recurrence. This review explores recent findings on the molecular mechanisms implicated in cancer dormancy and investigates potential strategies to improve therapeutic interventions.

Recent findings: Research on cancer dormancy reveals a complex and multifaceted phenomenon. Providing a latent reservoir of tumor cells with reduced proliferation and enhanced drug-tolerance, dormant cancer cells emerge from a clonally diverse population after therapy or at metastatic sites. These cells exhibit distinct transcriptional and epigenetic profiles, involving the downregulation of Myc and mechanistic target of rapamycin (mTOR) pathways, and the induction of autophagy. Senescence traits, under the control of factors such as p53, also contribute significantly. The tumor microenvironment can either promote or prevent dormancy establishment, notably through the involvement of T and NK cells within the dormant tumor niche. Strategies to combat dormancy-related relapse include direct elimination of dormant tumor cells, sustaining dormancy to prolong survival, or awakening dormant cells to re-sensitize them to antiproliferative drugs.

Summary: Improving our understanding of cancer dormancy at primary and secondary sites provides valuable insights into patient care and relapse prevention.

Purpose of review: Breast cancer ranks first among gynecological cancer in India. It is associated with urbanization, changes in lifestyle and obesity. Hormones also play a crucial role in the development of breast cancer. Steroid hormones play critical role in development of breast cancer.

Recent finding: Breast cancer is caused due to alteration in different hormone expressions leading to genetic instability. Loss or gains of functions due to genetic instability were associated with the alterations in housekeeping genes. Up-regulation in c-myc, signal transducer and activator of transcription (STAT), CREB-regulated transcription coactivator (CRTC), and eukaryotic translation initiation factor 4E (eIF4E) may cause the development of breast cancer. Peptide hormones are commonly following the phosphoinositide 3-kinases (PI3K) pathway for activation of cell cycle causing uncontrolled proliferation. Although steroid hormones are following the Ras/Raf/mitogen-activated protein kinase (MEK) pathway, their hyper-activation of these pathways causes extracellular-signal-regulated kinase (ERK) and MAPK activation, leading to carcinogenesis.

Summary: Alteration in cell cycle proteins, oncogenes, tumor suppressor genes, transcription and translation factors lead to breast cancer. Apoptosis plays a vital role in the elimination of abnormal cells but failure in any of these apoptotic pathways may cause tumorigenesis. Hence, a complex interplay of hormonal and genetic factors is required to maintain homeostasis in breast cells. Imbalance in homeostasis of these hormone and genes may lead to breast cancer.

Purpose of review: In this review, we explore the potential of tertiary lymphoid structures (TLS) as predictive biomarkers in the response to immunotherapy for melanoma patients.

Recent findings: The significance of TLS as indicators predicting immunotherapy response becomes particularly pronounced. Melanoma, renowned for its aggressive characteristics, has undergone revolutionary transformations in treatment through immunotherapeutic interventions. Investigations have unveiled a compelling correlation between the presence of TLS in the melanoma tumor microenvironment and favorable responses to immunotherapy. These responses, characterized by heightened survival rates and improved clinical outcomes, imply that TLS might be pivotal in tailoring more efficient and personalized treatments for individuals with melanoma. The ongoing discourse regarding TLS as a predictive biomarker underscores the need for a meticulous examination of its potential in guiding clinical decisions and optimizing therapeutic strategies.

Summary: TLS show great promises as potential biomarkers to melanoma patient's outcomes in ICI treatment; however, more studies are needed to understand their mechanisms of actions and the long-term impact of their functionality.