The efficacy and off-target effects of immune checkpoint inhibitors (ICI) in cancer treatment vary among patients. Monocytes likely contribute to this heterogeneous response due to their crucial role in immune homeostasis. We conducted a systematic review and meta-analysis to evaluate the impact of monocytes on ICI efficacy and immune-related adverse events (irAEs) in patients with cancer. We systematically searched PubMed, Web of Science, and Embase for clinical studies from January 2000 to December 2023. Articles were included if they mentioned cancer, ICI, monocytes, or any monocyte-related terminology. Animal studies and studies where ICIs were combined with other biologics were excluded, except for studies where two ICIs were used. This systematic review was registered with PROSPERO (CRD42023396297) prior to data extraction and analysis. Monocyte-related markers, such as absolute monocyte count (AMC), monocyte/lymphocyte ratio (MLR), specific monocyte subpopulations, and m-MDSCs were assessed in relation to ICI efficacy and safety. Bayesian meta-analysis was conducted for AMC and MLR. The risk of bias assessment was done using the Cochrane-ROBINS-I tool. Out of 5787 studies identified in our search, 155 eligible studies report peripheral blood monocyte-related markers as predictors of response to ICI, and 32 of these studies describe irAEs. Overall, based on 63 studies, a high MLR was a prognostic biomarker for short progression-free survival (PFS) and overall survival (OS) hazard ratio (HR): 1.5 (95% CI: 1.21–1.88) and 1.52 (95% CI:1.13–2.08), respectively. The increased percentage of classical monocytes was an unfavorable predictor of survival, while low baseline rates of monocytic myeloid-derived suppressor cells (m-MDSCs) were favorable. Elevated intermediate monocyte frequencies were associated but not significantly correlated with the development of irAEs. Baseline monocyte phenotyping may serve as a composite biomarker of response to ICI; however, more data is needed regarding irAEs. Monocyte-related variables may aid in risk assessment and treatment decision strategies for patients receiving ICI in terms of both efficacy and safety.

Gaining significant attention in recent years, starvation therapy based on the blocking nutrients supply to cancer cells via blood occlusion and metabolic interventions is a promisingly novel approach in cancer treatment. However, there are many crucial obstacles to overcome to achieve effective treatment, for example, poor-targeting delivery, cellular hypoxia, adverse effects, and ineffective monotherapy. The starvation-based multitherapy based on multifunctional nanomaterials can narrow these gaps and pave a promising way for future clinical translation. This review focuses on the progression in nanomaterials-mediated muti-therapeutic modalities based on starvation therapy in recent years and therapeutic limitations that prevent their clinical applications. Moreover, unlike previous reviews that focused on a single aspect of the field, this comprehensive review presents a broader perspective on starvation therapy by summarising advancements across its various therapeutic strategies.

The landscape of cancer treatment has shifted from histology-specific to tissue-agnostic approaches, targeting molecular alterations regardless of tumor origin. Currently, six pan-cancer biomarkers—NTRK, BRAF V600E, RET, HER2-positive, MSI-high, and TMB-high—along with nine molecularly targeted therapies have expanded treatment options across diverse malignancies. This review examines each biomarker’s molecular basis, prevalence across tumor types, and corresponding FDA-approved therapies. Additionally, emerging candidates—including FGFR, ALK, MET, ROS1, NRG1, PIK3CA, AKT, KRAS G12C, HER2 mutations, HER2-low/ultralow, B7-H3, and tumor-infiltrating lymphocytes (TILs)—are explored. While these biomarkers represent a paradigm shift in oncology, their integration into clinical practice requires overcoming challenges related to tumor heterogeneity and lineage-specific molecular dependencies. Future research should focus on identifying novel biomarkers, optimizing treatment strategies through multiomic analyses, and leveraging innovative clinical trial designs to advance precision oncology. In particular, further investigation into TILs as a predictive biomarker for immunotherapy is warranted, given their distinct immunophenotypic features and prognostic significance in shaping treatment responses across cancer types.Graphical Abbreviations: ADC, antibody–drug conjugate; AKT, protein kinase B; ALK, anaplastic lymphoma kinase; APC, antigen-presenting cell; B7-H3, B7 homolog 3; BRAF, B-raf proto-oncogene; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; DNA, deoxyribonucleic acid; ERK, extracellular signal-regulated kinase; FGFR, fibroblast growth factor receptor; GzmB, granzyme B; HER, human epidermal growth factor receptor; IFNγ, interferon-gamma; KRAS, Kirsten rat sarcoma viral oncogene homolog; MEK, mitogen-activated protein kinase kinase; MET, mesenchymal-epithelial transition factor; MSI, microsatellite instability; mTOR, mechanistic target of rapamycin; NRG1, neuregulin 1; NTRK, neurotrophic tyrosine receptor kinases; PD-1, programmed death receptor-1; PFN, perforin; PI3K, phosphoinositide 3-kinase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RET, rearranged during transfection; ROS1, proto-oncogene receptor tyrosine kinase 1; T-DXd, fam-trastuzumab deruxtecan-nxki; TIL, tumor-infiltrating lymphocytes; TKI, tyrosine kinase inhibitor; TMB, tumor mutation burden; TNFα, tumor necrosis factor-alpha.

There is abundant but discrepant scientific literature reporting an effect of opioids on the course of cancer. The International Agency for Research on Cancer monographs recently classified opium consumption as carcinogenic to humans in certain organs, raising concerns this may be due at least in part to the alkaloids opium contains (such as morphine and codeine). This systematic review investigated whether opioid exposure among cancer-free individuals is independently associated with the risk of future cancer incidence or cancer mortality. An electronic database search was conducted in PubMed, EMBASE, Web of Science, PsycINFO, International Pharmaceutical s, CINAHL and Scopus. Studies were included if they provided a statistical estimate of cancer mortality, cancer incidence, or cancer risk following opioid exposure. Study quality was assessed using the Newcastle–Ottawa Scale. Study characteristics and outcomes were extracted and analysed in a descriptive narrative synthesis. There were 27 studies that met the inclusion criteria, representing a total of 4,542,745 participants. Twelve of the 27 were rated as high quality according to the Newcastle–Ottawa Scale. The observed data is consistent with a small increase in the risk of cancer incidence or cancer mortality following opioid exposure, particularly in a subset of organs. There is, however, considerable uncertainty in the evidence given the substantial risk of bias in estimating the overall effect of opioid exposure on cancer outcomes in these studies. This review synthesises studies reporting cancer risk following opioid exposure and identifies the key methodological factors influencing ongoing uncertainty estimating the true effect. Rigorous epidemiological studies employing specific methods to minimize bias are warranted.

The emergence of CRISPR-Cas9 technology has transformed functional genomics, offering unmatched opportunities to dissect and understand biological pathways and identify novel therapeutic targets in cancer. Breast cancer is a complex, heterogeneous disease and remains a major cause of morbidity and mortality in women, particularly when diagnosed at advanced or metastatic stages where effective treatments are limited. High-throughput CRISPR screening is undoubtedly a powerful tool to discover novel drug targets, uncover synthetic lethal interactions, and identify vulnerabilities in cancer. This review focuses on advances in our understanding of breast cancer developed through CRISPR-based screening technology, particularly in identifying drivers of breast cancer progression, growth, and metastasis, as well as in identifying potential new therapeutic targets and combination therapies. We discuss recent discoveries, current challenges, and limitations of this approach and explore how advancements in CRISPR technology could have a profound impact on the future of breast cancer treatment.

The two most common and mutually exclusive driver mutations in non-small cell lung cancer affect EGFR and KRAS oncogenes. While EGFR mutations typically arise in non-smokers and are correlated with non-inflamed tumor microenvironment, KRAS mutations are associated with tobacco smoking, high mutational burden, and immunologically more active tumors. Consequently, current cancer immunotherapies have failed in patients with EGFR mutations, while patients with KRAS mutations have more favorable outcomes. The distinctive properties of the tumor immune microenvironment can partly explain the differences in the treatment outcomes. Besides the undeniable role of T lymphocytes, other immune cell types, cancer-associated fibroblasts, immunomodulatory cytokines, and angiogenesis are emerging as important players in these tumors. This article summarizes the current knowledge about the impact of EGFR versus KRAS mutations, among other mutations, on the tumor microenvironment and immunotherapy responses in lung cancer, highlighting the possible clinical implications for present and upcoming immunotherapy regiments, as well as emphasizing the gaps in the current knowledge that should be further investigated.

Centrosomes serve as microtubule-organizing organelles that function in spindle pole organization, cell cycle progression, and cilia formation. A non-canonical role of centrosomes that has gained traction in recent years is the ability to act as signal transduction centers. Centrosome amplification, which includes numerical and structural aberrations of centrosomes, is a candidate hallmark of cancer. The function of centrosomes as signaling centers in cancer cells with centrosome amplification is poorly understood. Establishing a model of how cancer cells utilize centrosomes as signaling platforms will help elucidate the role of extra centrosomes in cancer cell survival and tumorigenesis. Centrosomes act in a diverse array of cellular processes, including cell migration, cell cycle progression, and proteasomal degradation. Given that cancer cells with amplified centrosomes exhibit an increased number and larger area of these signaling platforms, extra centrosomes may be acting to promote tumor development by enhancing signaling kinetics in pathways that are essential for the formation and growth of cancer. In this review, we identify the processes centrosomes are involved in as signal transduction platforms and highlight ways in which cancer cells with centrosome amplification may be taking advantage of these mechanisms.

Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical involvement of specific mitochondrial-associated events, including mitochondrial quality control, intercellular mitochondrial transfer, and mitochondrial genetics, in potentiating the metastatic cascade of neoplastic cells. Furthermore, numerous recent studies have consistently emphasized the highly significant role mitochondria play in coordinating the regulation of tumor-infiltrating immune cells and immunotherapeutic interventions. This review provides a comprehensive and rigorous scholarly investigation of this subject matter, exploring the intricate mechanisms by which mitochondria contribute to tumor metastasis and examining the progress of mitochondria-targeted cancer therapies.

The expression “lost at sea” means to be confused or perplexed. By extension, lost at SCLC references the current confusion about how to circumvent the chemoresistance, particularly platinum resistance, which so plagues the treatment of extensive-stage small cell lung cancer (ES-SCLC) that in 2012 the US National Cancer Institute (NCI) designated it a “recalcitrant cancer.” Over a decade later, despite the approval of immune checkpoint inhibitors and the conditional approval of lurbinectedin, the prognosis for ES-SCLC, and especially platinum-resistant ES-SCLC, has scarcely improved. The focus of this review, which briefly summarizes current treatment options for ES-SCLC, is on five clinical-stage therapies with the potential to successfully reverse the platinum resistance that is perhaps the biggest obstacle to better clinical outcomes.