Onco, Volume 4, Issue 4 (December 2024) – 14 articles

Background: Patients with lung cancer experience higher rates of hospitalization due to their elevated mortality and associated comorbidities. Hospital admissions among oncology patients often indicate organ vulnerability and are linked to poor prognosis. This study aimed to assess the characteristics and potential prognostic factors of hospitalized lung cancer patients. Methods: We retrospectively analyzed 646 patients admitted from June 2021 to May 2022 to the Medical Oncology Service at La Paz University Hospital (Madrid, Spain). Results: During this period, 158 patients admitted had lung cancer (24.5%). The median overall survival since admission (mOSSA) was 3.3 months (95%CI: 1.86–7.74). In the univariate analysis, poorer mOSSA was associated with admission for tumor-related causes (1.33 vs. 7.30 months, p < 0.001), ECOG ≥ 2 (2.43 vs. 8.50 months, p < 0.001), NLR ≥ 6 (1.87 vs. 7.40 months), PNI ≤ 40 (1.67 vs. 4.97 months), and LDH ≥ 210 (2.27 vs. 7.87 months, p = 0.044). In the multivariate analysis, independent prognostic factors included admission for tumor-related causes (p = 0.032, aHR 1.81, 95%CI: 1.05–3.11) and ECOG ≥ 2 (p = 0.041, aHR 1.80, 95%CI: 1.03–3.16). Conclusions: Hospital admission for lung cancer is a poor prognostic event, particularly when associated with tumor-related causes or a decline in performance status. Full article

Immune checkpoint blockade (ICB), radiotherapy, chemotherapy and surgery are currently used as therapeutic strategies against melanoma, lung, bladder and renal cancers, but their efficacy is limited. Thus, I need to predict treatment response and resistance to address this challenge. In this study, I analyzed 350 lung cancer, 320 melanoma, 215 bladder cancer, 139 head and neck cancer and 151 renal carcinoma patients treated with ICB to identify tumor mutations associated with response and resistance to treatment. I identified several tumor mutations linked with a difference in survival outcomes following ICB. In lung cancer, missense mutations in ABL1, ASXL1, EPHA3, EPHA5, ERBB4, MET, MRE11A, MSH2, NOTCH1, PAK7, PAX5, PGR, ZFHX3, PIK3C3 and REL genes were indicative of favorable responses to ICB. Conversely, mutations in TGFBR2, ARID5B, CDKN2C, HIST1H3I, RICTOR, SMAD2, SMAD4 and TP53 genes were associated with shorter overall survival post-ICB treatment. In melanoma, mutations in FBXW7, CDK12, CREBBP, CTNNB1, NOTCH1 and RB1 genes predict resistance to ICB, whereas missense mutations in FAM46C and RHOA genes are associated with extended overall survival. In bladder cancer, mutations in HRAS genes predict resistance to ICB, whereas missense mutations in ERBB2, GNAS, ATM, CDKN2A and LATS1 genes, as well as nonsense mutations in NCOR1 and TP53 genes, are associated with extended overall survival. In head and neck cancer, mutations in genes like PIK3CA and KRAS correlated with longer survival, while mutations in genes like TERT and TP53 were linked to shorter survival. In renal carcinoma, mutations such as EPHA5, MGA, PIK3R1, PMS1, TSC1 and VHL were linked to prolonged overall survival, while others, including total splice mutations and mutations in B2M, BCOR, JUN, FH, IGF1R and MYCN genes were associated with shorter overall survival following ICB. Then, I developed predictive survival models by machine learning that correctly forecasted cancer patient survival following ICB within an error between 5 and 8 months based on their distinct tumor mutational attributes. In conclusion, this study advocates for personalized immunotherapy approaches in cancer patients. Full article

Anaplastic thyroid cancer (ATC) is considered to be one of the most virulent, treatment-refractory malignancies. Recent molecular insights into the biology of thyroid cancer have transformed ATC management, and BRAF/MEK targeted therapy is now incorporated into guideline-based multidisciplinary care. We report visceral perforation in the setting of an extreme response to such therapy in a patient with ATC. Molecularly targeted therapy afforded a dramatic but life-threatening response to treatment. This report highlights the complexities of care for the patient and treating clinicians. Full article

Background: Locally advanced rectal cancer (LARC) presents a significant treatment challenge. Transarterial chemoembolization (TACE) has emerged as a potential adjunctive treatment, offering targeted delivery of chemotherapeutic agents to the tumor site, minimizing systemic exposure. This systematic review aims to assess the current literature on this novel technique and evaluate the safety and efficacy profile of TACE in treating this complex cohort of patients. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, and Cochrane Library, to identify studies evaluating TACE in LARC. Inclusion criteria encompassed clinical trials, cohort studies, and case series reporting on outcomes such as tumor response rate, overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results: A total of eight studies involving 543 patients met the inclusion criteria. The studies varied in design, with five prospective and three retrospective studies. A higher prevalence of male participants (68.7%) was noted, with a median age of 60.3 years. The studies primarily evaluated the efficacy and safety of TACE in LARC treatment. Pathological response rates, tumor reduction, and survival outcomes varied across studies, with TACE showing promise in reducing tumor size, improving survival, and controlling metastasis. Major complications were rare, reported in 6.0% of cases. Conclusions: TACE is a promising therapeutic option for patients with LARC, demonstrating favorable tumor response rates and manageable toxicity profiles. Further large-scale, randomized controlled trials are warranted to confirm these findings and better define the role of TACE in the multimodal treatment of LARC. Full article

Background: Exercise has beneficial effects on cancer and its treatment, but the underlying mechanisms are poorly understood. Some studies have linked the positive impact of exercise to catecholamine signaling. In contrast, cancer stress studies have typically reported that catecholamines worsen cancer hallmarks and outcomes. Here, we aimed to investigate whether adrenergic receptor isoform expression can explain the contradictory effects of catecholamines in cancer. Methods: We cultured two pediatric sarcoma cancer cell lines that either express (A673 cell line) or do not express (RD cell line) adrenergic receptors. The cells were treated with a 5× dilution series of noradrenaline to assess the effects of noradrenaline on cell numbers. After these dose-finding experiments, we treated both cancer cell lines with 60 μM noradrenaline to examine its effect on cell proliferation and migration and cAMP signaling. Results: Treatment with 60 μM noradrenaline significantly decreased the cell numbers by 61.89% ± 10.36 (p ≤ 0.001), decreased cell proliferation by 15.88% ± 6.76 (p ≤ 0.05), decreased cell migration after 24 h (p ≤ 0.001), and increased cAMP concentrations 38-fold (p ≤ 0.001) in the A673 cells, which express adrenergic receptors, but not in the RD cells, which do not express adrenergic receptors. Conclusions: Our results indicate, as a proof of principle, that the effects of catecholamines on cancer progression and metastasis might depend on the expressions of the nine adrenergic receptor isoforms. As cancers express adrenergic and other receptors differentially, this has implications for the response of cancers to exercise, stress, and medication and may help to further personalize cancer treatments. Full article

Background/Objectives: Brain cancers offer poor prognoses to patients accompanied by symptoms that drastically impact the patient and their family. Brain tumours recruit local non-transformed cells to provide trophic support and immunosuppression within the tumour microenvironment, supporting tumour progression. Given the localisation and supportive role of pericytes at the brain vasculature, we explored the potential for brain pericytes to contribute to the brain cancer microenvironment. Methods: To investigate this, primary brain pericytes were treated with factors commonly upregulated in brain cancers. Immunofluorescent labelling identified changes to brain pericyte cell signalling, cytometric bead array measured inflammatory secretion, and flow cytometry investigated brain pericyte phagocytosis. Results: The TGFβ superfamily cytokines TGFβ and GDF-15 activated SMAD2/3 and inhibited C/EBP-δ, revealing a potential mechanism behind the pleiotropic action of TGFβ on brain pericytes. IL-17 induced secretion of IL-6 without activating NFκB, STAT1, SMAD2/3, or C/EBP-δ signalling pathways. IL-27 and IFNγ induced STAT1 signalling and significantly reduced brain pericyte phagocytosis. The remaining brain cancer-derived factors did not induce a measured response, indicating that these factors may act on other cell types or require co-stimulation with other factors to produce significant effects. Conclusions: We identify several brain cancer-secreted factors which alter relevant brain pericyte functions. This reveals mechanisms through which brain tumours may regulate brain pericyte activity and these data start to uncover the supportive role these cells may play in brain cancers. Full article

Introduction: Glioblastoma is a fatal intracranial neoplasm that is refractory to treatment, with inevitable disease recurrence and progression to death. Marine-derived compounds, including those found in nutraceutical products, may provide therapeutic benefit in the setting of glioblastoma. We present two patient cases whose courses demonstrate a compelling role for marine-derived products in the management of glioblastoma. Cases: Case 1 describes a patient with MGMT promoter unmethylated glioblastoma who went on to complete standard of care chemoradiation along with concurrent use of a majority sea cucumber (MSC) blend known as SeaCare^® (SeaCare, Torrington, CT, USA). Her survival of over 2 years significantly exceeds the recognized median survival time of glioblastoma. Case 2 describes a patient with a complicated course who experienced dramatic improvement after the initiation of the MSC blend, with an exceptional survival time of over 4 years post-diagnosis. Discussion: The mechanisms of marine-derived products that underlie these dramatic clinical effects are likely multifaceted but may hinge on the modification of the tumor immune microenvironment and suppression of tumorigenic effects. Specifically, the change in tumor-associated macrophages (TAMs) within the tumor microenvironment is central to this complex interplay. Conclusions: Ultimately, the use of marine products in the treatment of glioblastoma may present a novel and promising therapeutic strategy that warrants further investigation. Full article

(1) Background: Glioblastoma (GBM) is the most common malignant brain tumor in adults. Due to a lack of level 1 evidence, there is no clear consensus on the optimal extent of resection to improve overall survival. This umbrella review aggregates existing meta-analyses (MAs) to assess overall survival in patients undergoing subtotal resection (STR) versus gross total resection (GTR). (2) Methods: A systematic search of PubMed, Scopus, and Web of Science identified 441 studies, with four MAs meeting inclusion criteria. Data were analyzed using the metaumbrella R package, focusing on overall survival. Quality was assessed using AMSTAR2, with scores ranging from 0 to 11. The Ioannidis criteria were applied to evaluate the credibility of the evidence. (3) Results: The quality assessment rated all four studies highly, with a mean AMSTAR2 score of 10.25. The pooled analysis revealed a significant survival advantage for GTR over STR. However, the Ioannidis classification graded the evidence as Class III, indicating weak credibility. (4) Conclusions: GTR offers a slight survival benefit over STR in GBM patients, but the credibility of the evidence is weak, highlighting the need for further research. Full article

Isocitrate dehydrogenase wild-type glioblastoma, a Grade 4 malignant brain neoplasm, remains resistant to multimodal treatment, with a median survival of 16 months from diagnosis with no geographical bias. Despite increasing appreciation of intra-tumour genotypic variation and stem cell plasticity, such knowledge has yet to translate to efficacious molecular targeted therapies in this post-genomic era. Critically, the manifestation of molecular heterogeneity and stem cell biological process within clinically relevant infiltrative disease is little understood. Here, we review the interactions between neural plasticity, intra-tumour heterogeneity and residual infiltrative disease, and we draw upon antibiotic resistance as an insightful analogy to further explain tumour heterogeneity. Full article

Raman spectroscopy is a technique which involves quantitative and qualitative molecular analysis based on the interaction between incident light and isolation of scattered wavelengths in generating a molecular fingerprint. It has a broad array of potential scientific applications, encompassing areas as diverse as food science and forensics. However, it may also be highly useful in clinical oncology. A recent focus of research in oncology has been in achieving the individualisation of care. Two important strategies to achieve a so-called “precision oncology” approach may include the detection of circulating tumour DNA (ctDNA) in more objectively evaluating treatment response and guiding de-escalation and intensification approaches in systemic therapy and therapeutic drug monitoring (TDM). Therapeutic drug monitoring involves the quantitation of plasma drug levels in order to tailor medication dosing in optimizing outcomes. The existing approaches to characterize small molecules, such as fluorescence-based and chromatographic strategies, may be limited by high costs, long turnaround times, and bulky equipment. Surface-enhanced Raman spectroscopy (SERS) may be deployed by utilizing a handheld device, with the potential for point of care, rapid turnaround, low-cost assessment of clinically relevant parameters, and prompt implementation of attendant changes in treatment. Although there is a growing body of data supporting the implementation of TDM and evaluation of ctDNA in achieving precision medicine, the uptake of such approaches remains relatively limited outside of clinical trials. As stated, the nature of existing analytical methodologies may prove to be a significant barrier to the routine clinic-based implementation of such approaches. Therefore, we provide the existing evidence for SERS in alleviating these barriers. We also provide insights into how SERS could contribute to clinical oncology. Full article

Chromosomal instability and DNA damage are hallmarks of cancers that can result in the accumulation of micronuclei, cytosolic chromatin fragments (CCFs), or cytosolic DNA species (cytoDNA). The cyclic GMP-AMP synthase (cGAS) is a DNA sensor that recognizes cytosolic DNA and chromatin fragments and subsequently triggers a systemic type I interferon response via the cGAS-STING pathway. Although cancer cells usually contain a high level of chromosomal instability, these cells can avoid the induction of the interferon (IFN) response either by silencing cGAS-STING or the upregulation of the three prime exonuclease 1 (TREX1). TREX1 restricts the spontaneous activation of the cGAS-STING pathway through the degradation of cytoDNA; this in turn limits tumor immunogenicity allowing cancer cells to evade immune detection. Deletion of TREX1 in different cancer types has been shown to decrease tumor growth and increase tumor immune infiltration in pre-clinical mice models. These recent studies also showed the efficacy of TREX1-targeting in combination with anti-PD-1 immune checkpoint blockade. Therefore, targeting TREX1 represents a unique therapeutic strategy to induce an amplified induction of a type I IFN response, promoting the host’s immune response against chromosomally unstable cancer cells. We here discuss these recent advances obtained in preclinical cancer models that pave the way to develop TREX1 inhibitors and to find new avenues to target the broad cGAS-STING pathway signaling in cancer therapy. Full article

Cancer, one of the leading causes of death worldwide, is on the rise. The high toxicity of conventional chemotherapy, often applied as drug cocktails, and the development of resistance limit the use of antineoplastic drugs and reduce the quality of life. With easier access, a growing number of patients are using cannabis (cannabinoids) for alleviation of their symptoms, and in the hope of improving survival. This article summarizes results observed with combinations of phytocannabinoids and standard chemotherapeutic agents in animal tumour models and in patients. It is limited to approved phytocannabinoids. Preliminary preclinical data suggest that conventional antineoplastic agents combined with cannabinoids exert enhanced anti-cancer effects, reduce resistance development and improve survival. Corresponding experiences with patients are still very limited and only concern a few patients with glioblastoma and pancreatic cancer. Benefits of combinations containing cannabinoids have also been reported for chemotherapy-induced nausea and vomiting, loss of appetite (dronabinol), and chemotherapy-induced peripheral neuropathic pain and anxiety (cannabidiol). In addition, phytocannabinoids, particularly cannabidiol, may play a role in protecting organs such as the heart, lungs or kidneys from chemotherapy-related toxicity. Although the results are promising, more research is needed to ensure whether the benefits of adjuvant cannabinoids outweigh the potential risks. Full article

Background: For patients with head and neck squamous cell carcinoma (HNSCC), after a single or multi-modality treatment, a specific follow-up strategy is needed, but there is no agreement between the main international societies on the proper methods and timing of follow-up. Methods: We performed a descriptive review to evaluate the available data and compare the main guidelines, giving some practical guidance to perform effective personalized follow-up strategies. Results and Conclusions: While clinical and endoscopic follow-up alone seems to be appropriate for early-stage HNSCCs, the addition of close radiologic follow-up in locally advanced HNSCCs is still debated, as there are no data indicating that an earlier detection of recurrence correlates with increased survival, while it is mandatory in the first three-six months to define the response to treatment. For patients who have undergone conservative surgery or have major pathological risk factors, the incidence of locoregional recurrence is higher, and locoregional radiologic follow-up (magnetic resonance imaging is preferred to computed tomography) should be considered. Positron emission tomography may be useful in cases of suspected locoregional persistence of disease, differentiating it from post-irradiation outcomes. Distant radiological follow-up can be considered in the detection of the second primary in cases of specific risk factors and for virus-related tumors. For the latter, the use of circulating DNA should always be considered. A brain scan is not recommended without specific symptoms. For all patients who do not fall into the above categories, clinical and endoscopic follow-up should be proposed, reserving radiological investigations only at the onset of symptoms. Full article

The epidermal growth factor receptor (EGFR) plays a critical role in regulating essential cellular processes that are frequently hijacked to promote cancer. In colorectal cancer (CRC) in particular, the EGFR signaling pathway is frequently hyperactivated via receptor and/or ligand overexpression and downstream oncogenic mutations. Current EGFR-targeted therapies for metastatic CRC (mCRC) include the mAbs cetuximab and panitumumab. However, intrinsic and acquired resistance to EGFR-targeted mAbs are commonly observed. Thus, additional biomarkers are necessary to better understand patient sensitivity to EGFR-targeted therapies. Furthermore, therapeutic targeting of alternative EGFR pathway components may serve as one mechanism to overcome EGFR-targeted mAb resistance. In this review, we discuss the mounting evidence supporting EGFR ligands epiregulin (EREG) and amphiregulin (AREG), which are overexpressed in CRC with potential key roles in tumor progression, as predictive biomarkers for EGFR-targeted therapy sensitivity, as well as mediators of therapy resistance, though further studies are necessary to validate the prognostic roles and mechanisms by which these ligands contribute to resistance. Additionally, we review recent advances towards therapeutic targeting of EREG and AREG in cancer through the development and use of EREG- and AREG-targeted mAbs as well as antibody–drug conjugates (ADCs). We conclude with a discussion on the roadblocks to clinical implementation of EREG and AREG as biomarkers, as well as approaches to enhance the efficacy of current EREG- and AREG-targeted strategies. Full article