Cancer Research UK and NIHR-funded scientists at the University of Cambridge create a tool which allows them to find some vulnerable tumours. Over 4,000 tumours from seven types of cancers were analysed, with scientists creating an algorithm that picks out cancers which are unable to fix errors in their DNA when growing. The algorithm could help doctors figure out which patients are more likely to have successful immunotherapy treatment.

A new study conducted by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has uncovered a key mechanism behind lenalidomide resistance in multiple myeloma (MM), offering new insights into potential strategies for improving treatment outcomes and overcoming drug resistance.

The team, led by Dr Teoh Phaik Ju and Dr Koh Mun Yee, together with Professor Chng Wee Joo and Associate Professor Polly Chen, identified a gene called ADAR1, which encodes an RNA editing enzyme, as a key factor in suppressing the immune response triggered by lenalidomide—an immune-stimulating drug, essential to kill MM cells. The findings were published in the high-impact scientific journal Blood on 13 March 2025.

ADAR1’s role in lenalidomide resistance in MM

MM is a type of cancer that affects plasma cells in the bone marrow. While standard-of-care treatments like lenalidomide, an immunomodulatory drug (IMiD), have improved survival rates for many MM patients, a significant number still experience relapse due to the development of drug resistance.

Lenalidomide works by binding to a protein called cereblon (CRBN), which breaks down several proteins that are essential for MM cell survival and growth. However, many patients eventually stop responding to the drug, leading to disease relapse. While 20 to 30 per cent of the resistance cases have been linked to defects in CRBN and its associated factors, the underlying mechanisms in most resistance cases have remained poorly understood. This study reports new findings demonstrating that ADAR1 abnormalities lead to a suppressed immune system in IMiD-resistant MM cases.

Overcoming drug resistance

ADAR1 inhibits lenalidomide’s activity by editing double-stranded RNA (dsRNA), thus hindering the immune response and reducing the effectiveness of the drug in combating MM growth and proliferation. The researchers discovered that by reducing the levels of ADAR1 and increasing dsRNA accumulation in MM cells, they could increase the sensitivity of the cells to lenalidomide. This would, in turn, lead to the activation of the immune responses and kill the MM cells. The discovery adds a new layer to the understanding of how MM patients may become resistant to IMiD, highlighting the role of dsRNA pathways beyond the previously understood CRBN pathway.

The findings also suggest that targeting ADAR1 and the dsRNA pathway could offer promising strategies to overcome resistance to lenalidomide in MM. As clinical trials continue to explore the potential of new IMiD analogues, such as CRBN-E3 ligase modulators (CELMoDs) and other drugs with similar pharmacological profile, combining these treatments with ADAR1 inhibitors may provide a more effective approach to tackle drug resistance and improve patient outcomes.

With ADAR1 inhibitors currently in preclinical development, this strategy holds great promise for advancing treatment options for MM. In addition, the research team plans to further investigate ADAR1’s role in alternative splicing, a post-transcriptional gene regulatory mechanism, in MM, which could uncover even more opportunities for treatments.

Background

Semi-rigid and large bore (≥ Fr 24) polyvinyl chloride (PVC) drains are routinely used for the evacuation of fluid and air from the pleural space following video-assisted thoracoscopic surgery (VATS) lung resections. The rigidity and caliber of these drains are widely recognized as significant contributors to postoperative pain. Inadequate pain management can thereby compromise respiratory efficiency, coughing, and patient mobility, potentially precipitating respiratory complications like atelectasis and pneumonia (1-7). In VATS, postoperative pain has been commonly assessed through a combination of methods, including pain scales, analgesic consumption analysis, and functional evaluation tests (5,8-12).

Rationale and knowledge gap

In recent years, significant efforts have been made to minimize drain-related postoperative pain by modifying and improving the methods of chest drainage. Since one or two large bore drains (≥ Fr 24) are still commonly used to ensure effective drainage of air leaks, improvements have also been directed towards the materials used for the drains (1-4,7).

Hence, there has been growing adoption of softer silicone (SIL) drains, purportedly offering reduced patient discomfort without compromising drainage efficacy compared to standard PVC drains. Previous studies have demonstrated the efficacy of SIL drains in fluid management and suggested potential pain reduction following diverse chest procedures, encompassing VATS and open surgeries (1-4,13,14). However, the benefit of SIL drains in reducing postoperative pain after VATS anatomical lung resections has not yet been clearly demonstrated, and postoperative pain remains a significant concern.

Objective

The objective of our prospective randomized study was to evaluate the impact of coaxial SIL drains on postoperative pain, drainage efficacy, short-term treatment outcome, and costs following VATS lobectomy, in comparison to standard PVC drains. Authors hypothesized that patients receiving a coaxial SIL drain would require less analgesia and demonstrate greater respiratory muscle strength. Furthermore, authors anticipated that drainage efficacy and short-term treatment outcome would be comparable between the two groups.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma, a distinctive subtype of non-Hodgkin’s lymphoma (1), exemplifies primary extranodal lymphomas originating in the lung (2). Renowned for its indolent nature and infrequent occurrence, the clinical presentation of pulmonary MALT lymphoma is subtle (3), and its radiological manifestations are diverse, posing considerable diagnostic challenges (4). In contrast to more aggressive lymphomas, MALT lymphoma often lacks the hallmark symptoms of high-grade malignancies (5), making early detection elusive and potentially causing delays in therapeutic intervention.

Clinical manifestations of MALT lymphoma may vary but often include non-specific symptoms such as cough, chest pain, or shortness of breath (6,7). Systemic symptoms, such as fever and weight loss, are less common but can occur (8). The overall incidence of pulmonary MALT lymphoma is relatively low compared to other lymphomas (9,10). Risk factors for developing pulmonary MALT lymphoma may include a history of autoimmune diseases, chronic infections, or exposure to environmental factors that trigger chronic inflammation (11).

The treatment landscape for pulmonary MALT lymphoma primarily revolves around surgical resection, radiotherapy, and chemotherapy, with surgery being the preferred modality for localized disease (12,13). The indolent course of MALT lymphoma, coupled with its relative insensitivity to chemotherapy and radiotherapy, underscores the importance of accurate diagnosis and appropriate selection of treatment modality (14,15). Moreover, the prognosis of MALT lymphoma is generally favorable, with surgical interventions yielding better outcomes compared to cases where complete resection is not feasible (16).

The clinical significance of pulmonary MALT lymphoma transcends its rarity, delving into the domain of differential diagnosis (17). This is particularly critical when distinguishing it from prevalent pulmonary pathologies like adenocarcinomas, focal invasive mucinous adenocarcinoma of the lung, focal organizing pneumonia or infectious granulomas (18,19). The management and prognosis of these conditions vary significantly, underscoring the importance of accurate differentiation. The complexity of pulmonary MALT lymphoma is further complicated by its etiology, commonly associated with chronic inflammatory stimuli (20). This association is notable, especially in patients with autoimmune diseases or a history of chronic infections, adding layers of intricacy to the understanding of the disease (21,22).

Radiologically, pulmonary MALT lymphoma displays a spectrum of patterns on high-resolution computed tomography (HRCT), ranging from solitary or multiple nodules, areas of consolidation, to ground-glass opacities (23,24). These imaging features, although valuable, overlap significantly with those of other pulmonary conditions, thereby necessitating a more nuanced approach to interpretation (25,26). The role of imaging in MALT lymphoma extends to not only diagnosis but also to treatment planning and monitoring response to therapy. Pathologically, MALT lymphoma is characterized by the proliferation of marginal zone B-cells, which may manifest in a variety of cytological appearances (27). Immunohistochemistry plays a pivotal role in diagnosis, with markers such as CD20 and CD79a often showing positivity (28,29). The Ki67 proliferation index is another valuable tool, providing insights into the tumor’s growth dynamics (30). Ki67 indicates the level of cellular proliferation activity, representing the proliferation rate of MALT tumor cells. It reflects the degree of malignancy of the cells and is related to the prognosis of the patients. However, the lack of a histological grading system in MALT lymphoma contrasts with other lymphomas, where such grading significantly influences treatment decisions (31).

This study aimed to elucidate the imaging and pathological characteristics of pulmonary MALT lymphoma based on a comprehensive analysis of 20 cases from a thoracic specialty hospital. Our focus is to assist radiologists in understanding the disease’s unique imaging features from a pathological perspective, thereby improving differential diagnosis during initial chest imaging assessments. This understanding is critical in guiding further biopsy for definitive diagnosis and timely surgical intervention when feasible, or alternatively, opting for radiotherapy or chemotherapy.