bims-tumhet Biomed News
on Tumor Heterogeneity
Issue of 2024–02–04
sixteen papers selected by
Sergio Marchini, Humanitas Research
  1. Concordance between an FDA-approved companion diagnostic and an alternative assay kit for assessing homologous recombination deficiency in ovarian cancer.
  2. The role of aberrant DNA methylation in cancer initiation and clinical impacts.
  3. Aneuploidy and complex genomic rearrangements in cancer evolution.
  4. Evaluation of Homologous Recombination Deficiency in Ovarian Cancer.
  5. Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions.
  6. Applicability of Spatial Technology in Cancer Research.
  7. Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc.
  8. ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.
  9. Aneuploid serves as a prognostic marker and favors immunosuppressive microenvironment in ovarian cancer.
  10. Clinical Significance of Tumor Immune Microenvironment in Endometrial Endometrioid Carcinoma, Grade 1 With DNA Mismatch Repair Protein Loss.
  11. Beyond blood: Advancing the frontiers of liquid biopsy in oncology and personalized medicine.
  12. The yin and yang of chromosomal instability in prostate cancer.
  13. Does "One Size Fits All"? Rethinking FIGO Depth of Invasion Measurements in Vulvar Cancer.
  14. Spatial transcriptomics and single-nucleus RNA sequencing reveal a transcriptomic atlas of adult human spinal cord.
  15. Omics-based molecular classifications empowering in precision oncology.
  16. Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy.
  1. Gynecol Oncol. 2024 Jan 29. pii: S0090-8258(24)00023-4. [Epub ahead of print]184 67-73
    Concordance between an FDA-approved companion diagnostic and an alternative assay kit for assessing homologous recombination deficiency in ovarian cancer.
    Amy K Wehn, Ping Qiu, Jared Lunceford, Alexander Yarunin, Razvan Cristescu, Li Liu, Kyria Roessler, Sven Bilke, John R Day, Kirsten M Timms, Wilko Weichert, Matthew J Marton.
       OBJECTIVE: Authors evaluated the performance of a commercially available next-generation sequencing assay kit; this was based on genomic content from Illumina's TruSight™ Oncology 500 research assay that identifies BRCA variants and proprietary algorithms licensed from Myriad and, with additional genomic content, measures the homologous recombination deficiency (HRD) genomic instability score (GIS) in tumor tissue (TSO 500 HRD assay).
    METHODS: Data from the TSO 500 HRD assay were compared with data from the Myriad MyChoice®CDx PLUS assay (Myriad assay). Prevalence rates for overall HRD status and BRCA mutations (a deleterious or suspected deleterious BRCA1 or BRCA2 mutation or both) and assay agreement rates for HRD GIS and BRCA analysis were assessed in ovarian tumor samples. Pearson correlations of the continuous HRD GIS and analytic sensitivity and specificity were evaluated.
    RESULTS: The prevalence of overall HRD positivity was 51.2% (TSO 500 HRD assay) versus 49.2% (Myriad assay) and the prevalence of BRCA mutations was 27.6% (TSO 500 HRD assay) versus 25.5% (Myriad assay). After post-processing optimization, concordance of the HRD GIS was 0.980 in all samples and 0.976 in the non-BRCA mutation cohort; the area under the receiver operating characteristic curve was 0.995 and 0.992, respectively.
    CONCLUSIONS: Comparison between the Illumina and Myriad assays showed that overall HRD status, the individual components of BRCA analysis, and HRD GIS detection results were highly concordant (>93%), suggesting the TSO 500 HRD assay will approach the analytical accuracy of the FDA-approved Myriad assay.
    Keywords:  BRCA; Genomic instability score; Homologous recombination deficiency; Ovarian cancer
    DOI:  https://doi.org/10.1016/j.ygyno.2024.01.016
  2. Ther Adv Med Oncol. 2024 ;16 17588359231220511
    The role of aberrant DNA methylation in cancer initiation and clinical impacts.
    Franziska Geissler, Ksenija Nesic, Olga Kondrashova, Alexander Dobrovic, Elizabeth M Swisher, Clare L Scott, Matthew J Wakefield.
      Epigenetic alterations, including aberrant DNA methylation, are now recognized as bone fide hallmarks of cancer, which can contribute to cancer initiation, progression, therapy responses and therapy resistance. Methylation of gene promoters can have a range of impacts on cancer risk, clinical stratification and therapeutic outcomes. We provide several important examples of genes, which can be silenced or activated by promoter methylation and highlight their clinical implications. These include the mismatch DNA repair genes MLH1 and MSH2, homologous recombination DNA repair genes BRCA1 and RAD51C, the TERT oncogene and genes within the P15/P16/RB1/E2F tumour suppressor axis. We also discuss how these methylation changes might occur in the first place - whether in the context of the CpG island methylator phenotype or constitutional DNA methylation. The choice of assay used to measure methylation can have a significant impact on interpretation of methylation states, and some examples where this can influence clinical decision-making are presented. Aberrant DNA methylation patterns in circulating tumour DNA (ctDNA) are also showing great promise in the context of non-invasive cancer detection and monitoring using liquid biopsies; however, caution must be taken in interpreting these results in cases where constitutional methylation may be present. Thus, this review aims to provide researchers and clinicians with a comprehensive summary of this broad, but important subject, illustrating the potentials and pitfalls of assessing aberrant DNA methylation in cancer.
    Keywords:  BRCA-related cancers; diagnosis; epigenomics; genomic testing; genomics; homologous recombination deficiency; oncogenic driver mutations; targeted therapy; therapeutic resistance
    DOI:  https://doi.org/10.1177/17588359231220511
  3. Nat Cancer. 2024 Jan 29.
    Aneuploidy and complex genomic rearrangements in cancer evolution.
    Toby M Baker, Sara Waise, Maxime Tarabichi, Peter Van Loo.
      Mutational processes that alter large genomic regions occur frequently in developing tumors. They range from simple copy number gains and losses to the shattering and reassembly of entire chromosomes. These catastrophic events, such as chromothripsis, chromoplexy and the formation of extrachromosomal DNA, affect the expression of many genes and therefore have a substantial effect on the fitness of the cells in which they arise. In this review, we cover large genomic alterations, the mechanisms that cause them and their effect on tumor development and evolution.
    DOI:  https://doi.org/10.1038/s43018-023-00711-y
  4. Curr Treat Options Oncol. 2024 Feb 01.
    Evaluation of Homologous Recombination Deficiency in Ovarian Cancer.
    Rubina Ratnaparkhi, Melissa Javellana, Andrea Jewell, Lori Spoozak.
       OPINION STATEMENT: Homologous recombination deficiency (HRD) is an important biomarker guiding selection of ovarian cancer patients who will derive the most benefit from poly(ADP-ribose) polymerase inhibitors (PARPi). HRD prevents cells from repairing double-stranded DNA damage with high fidelity, PARPis limit single-stranded repair, and together these deficits induce synthetic lethality. Germline or somatic BRCA mutations represent the narrowest definition of HRD, but do not reflect all patients who will have a durable PARPi response. HRD can also be defined by its downstream consequences, which are measured by different metrics depending on the test used. Ideally, all patients will undergo genetic counseling and germline testing shortly after diagnosis and have somatic testing sent once an adequate tumor sample is available. Should barriers to one test be higher, pursuing germline testing with reflex to somatic testing for BRCA wildtype patients or somatic testing first strategies are both evidence-based. Ultimately both tests offer complementary information, germline testing should be pursued for any patient with a history of ovarian cancer, and somatic testing is valuable at recurrence if not performed in the upfront setting. There is a paucity of data to suggest superiority of one germline or somatic assay; therefore, selection should optimize turnaround time, cost to patients, preferred result format, and logistical burden. Each clinic should implement a standard testing strategy for all ovarian cancer patients that ensures HRD status is known at the time of upfront chemotherapy completion to facilitate comprehensive counseling about anticipated maintenance PARPi benefit.
    Keywords:  Genes, BRCA1*; Genes, BRCA2*; Germline; Homologous recombination deficiency; Ovarian cancer; Poly(ADP-ribose) polymerase inhibitors; Somatic
    DOI:  https://doi.org/10.1007/s11864-024-01176-6
  5. Am J Surg Pathol. 2024 Feb 01.
    Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions.
    Yen-Wei Chien, Yeh Wang, Peng Huang, Barrett Craig Lawson, David L Kolin, M Herman Chui, Russell Vang, Tricia A Numan, T Rinda Soong, Brant G Wang, Saron Ann Smith, Chi-Long Chen, Rebecca Stone, Christopher Douville, Tian-Li Wang, Ie-Ming Shih.
      Serous tubal intraepithelial carcinoma (STIC) is the fallopian tube precursor lesion for most cases of pelvic high-grade serous carcinoma (HGSC). To date, the morphologic, molecular, and clinical heterogeneity of STIC and a less atypical putative precursor lesion, termed serous tubal intraepithelial lesion, has not been well characterized. Better understanding of precursor heterogeneity could impact the clinical management of women with incidental STICs (without concurrent carcinoma) identified in cases of prophylactic or opportunistic salpingectomy. This study analyzed morphologic and molecular features of 171 STICs and 21 serous tubal intraepithelial lesions. We assessed their histologic features, Ki-67 and p53 staining patterns, and genome-wide DNA copy number alterations. We classified all precursor lesions into 2 morphologic subtypes, one with a flat surface (Flat) and the other characterized by budding, loosely adherent, or detached (BLAD) morphology. On the basis of pathology review by a panel of 8 gynecologic pathologists, we found 87 BLAD, 96 Flat, and 9 indeterminate lesions. As compared with Flat lesions, BLAD lesions were more frequently diagnostic of STIC (P<0.0001) and were found concurrently with HGSC (P<0.0001). BLAD morphology was also characterized by higher Ki-67 proliferation index (P<0.0001), presence of epithelial stratification (P<0.0001), and increased lymphocyte density (P<0.0001). BLAD lesions also exhibited more frequent DNA copy number gain/amplification at the CCNE1 or CMYC loci canonical to HGSCs (P<0.0001). Both BLAD morphology and STIC diagnoses are independent risk factors for an elevated Ki-67 proliferation index. No correlation was observed between BLAD and Flat lesions with respect to patient age, presence of germline BRCA1/2 mutation, or p53 staining pattern. These findings suggest that tubal precursor lesions are morphologically and molecularly heterogeneous, laying the foundation for further studies on the pathogenesis of HGSC initiation and identifying histologic features predictive of poor patient outcomes.
    DOI:  https://doi.org/10.1097/PAS.0000000000002187
  6. Cancer Res Treat. 2024 Jan 30.
    Applicability of Spatial Technology in Cancer Research.
    Sangjeong Ahn, Hye Seung Lee.
      This review explores spatial mapping technologies in cancer research, highlighting their crucial role in understanding the complexities of the tumor microenvironment (TME). The TME, which is an intricate ecosystem of diverse cell types, has a significant impact on tumor dynamics and treatment outcomes. This review closely examines cutting-edge spatial mapping technologies, categorizing them into capture-, imaging-, and antibody-based approaches. Each technology was scrutinized for its advantages and disadvantages, factoring in aspects such as spatial profiling area, multiplexing capabilities, and resolution. Additionally, we draw attention to the nuanced choices researchers face, with capture-based methods lending themselves to hypothesis generation, and imaging/antibody-based methods that fit neatly into hypothesis testing. Looking ahead, we anticipate a scenario in which multi-omics data are seamlessly integrated, artificial intelligence enhances data analysis, and spatiotemporal profiling opens up new dimensions.
    Keywords:  Cancer research; Spatial proteomics; Spatial transcriptomics; Tumor microenvironment
    DOI:  https://doi.org/10.4143/crt.2023.1302
  7. Genome Biol. 2024 Jan 31. 25(1): 38
    Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc.
    Alice Antonello, Riccardo Bergamin, Nicola Calonaci, Jacob Househam, Salvatore Milite, Marc J Williams, Fabio Anselmi, Alberto d'Onofrio, Vasavi Sundaram, Alona Sosinsky, William C H Cross, Giulio Caravagna.
      Copy number alterations (CNAs) are among the most important genetic events in cancer, but their detection from sequencing data is challenging because of unknown sample purity, tumor ploidy, and general intra-tumor heterogeneity. Here, we present CNAqc, an evolution-inspired method to perform the computational validation of clonal and subclonal CNAs detected from bulk DNA sequencing. CNAqc is validated using single-cell data and simulations, is applied to over 4000 TCGA and PCAWG samples, and is incorporated into the validation process for the clinically accredited bioinformatics pipeline at Genomics England. CNAqc is designed to support automated quality control procedures for tumor somatic data validation.
    DOI:  https://doi.org/10.1186/s13059-024-03170-5
  8. Ann Oncol. 2024 Jan 29. pii: S0923-7534(23)05103-7. [Epub ahead of print]
    ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.
    J A Ledermann, X Matias-Guiu, F Amant, N Concin, B Davidson, C Fotopoulou, A González-Martin, C Gourley, A Leary, D Lorusso, S Banerjee, L Chiva, D Cibula, N Colombo, S Croce, A G Eriksson, C Falandry, D Fischerova, P Harter, F Joly, C Lazaro, C Lok, S Mahner, F Marmé, C Marth, W G McCluggage, I A McNeish, P Morice, S Nicum, A Oaknin, J A Pérez-Fidalgo, S Pignata, P T Ramirez, I Ray-Coquard, I Romero, G Scambia, J Sehouli, R Shapira-Frommer, S Sundar, D S P Tan, C Taskiran, W J van Driel, I Vergote, F Planchamp, C Sessa, A Fagotti.
      The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
    Keywords:  chemotherapy; maintenance treatment; molecular biology; ovarian cancer; pathology; surgery
    DOI:  https://doi.org/10.1016/j.annonc.2023.11.015
  9. J Ovarian Res. 2024 Feb 02. 17(1): 30
    Aneuploid serves as a prognostic marker and favors immunosuppressive microenvironment in ovarian cancer.
    Ming Du, Qingqing Cai, Jiaan Sun, Mingxing Zhang, Shuo Zhang, Xiaoxia Liu, Mengyu Zhang, Xiaoyan Zhang.
      Ovarian cancer is the most lethal gynecologic neoplasm, and most patients experience recurrence and chemoresistance. Even the promising immunotherapy showed limited efficacy in ovarian cancer, probably due to the immunosuppressive microenvironment. However, the behind mechanisms of the immune exclusion or cold phenotype in ovarian cancer still remain to be explored. As a cancer dominated by copy number variations instead of mutations, ovarian cancer contains a high fraction of aneuploid, which might correlate with immune inhibition. Nevertheless, whether or how aneuploid affects ovarian cancer is still unclear. For exploring the role of aneuploid cancer cells and the potential ploidy-immune relationship, herein, the ploidy information was first comprehensively analyzed combining the karyotype data and copy number variation data obtained from Mitelman and cBioPortal databases, respectively. Ovarian cancer showed strong ploidy heterogeneity, with high fraction of aneuploid and recurrent arm-level and whole chromosome changes. Furthermore, clinical parameters were compared between the highly-aneuploid and the near-diploid ovarian cancers. Aneuploid indicated high grade, poor overall survival and poor disease-free survival in ovarian cancer. To understand the biofunction affected by aneuploid, the differentially expressed genes between the highly-aneuploid and the near-diploid groups were analyzed. Transcription data suggested that aneuploid cancer correlated with deregulated MHC expression, abnormal antigen presentation, and less infiltration of macrophages and activated T cells and higher level of T cell exclusion. Furthermore, the ploidy-MHC association was verified using the Human Protein Atlas database. All these data supported that aneuploid might be promising for cancer management and immune surveillance in ovarian cancer.
    Keywords:  Aneuploid; Antigen presentation; Chromosome alteration; Immune microenvironment; Ovarian cancer
    DOI:  https://doi.org/10.1186/s13048-024-01356-w
  10. Int J Gynecol Pathol. 2024 Jan 22.
    Clinical Significance of Tumor Immune Microenvironment in Endometrial Endometrioid Carcinoma, Grade 1 With DNA Mismatch Repair Protein Loss.
    Kazuhisa Hachisuga, Minoru Kawakami, Hiroshi Tomonobe, Shoji Maenohara, Keisuke Kodama, Hiroshi Yagi, Masafumi Yasunaga, Ichiro Onoyama, Kazuo Asanoma, Hideaki Yahata, Yoshinao Oda, Kiyoko Kato.
      The administration of immune checkpoint inhibitors (ICIs) is increasing in endometrial cancer, especially in the mismatch repair (MMR)-deficient group. To prevent unnecessary immune-related adverse events, ICIs need to be administered to more appropriate patients. The tumor immune microenvironment has been reported to be a predictive marker of the efficacy of ICI therapies. This study evaluated CD8, FoxP3, CD68, PD-L1, and β-catenin expression in endometrial endometrioid carcinoma, grade 1 (G1) with DNA mismatch repair protein loss (MMR loss), and their association with clinicopathological features. We retrospectively analyzed tumor samples from 107 patients with endometrial endometrioid carcinoma, G1 (MMR-deficient group: n=67; MMR-proficient group: n=40). Overall, 47 cases of MLH1/PMS2 loss and 20 cases of MSH2/MSH6 loss were observed. The patients with low intraepithelial CD8 expression significantly more frequently exhibited deep myometrial invasion, and the elderly group (≥60 y) significantly more frequently showed low stromal CD8 expression. In addition, FoxP3-positive cell count and FoxP3/CD8+ ratio were significantly correlated with the International Federation of Obstetrics and Gynecology 2023 stage and lymph node metastasis. In the Kaplan-Meier analysis, the patients with low intraepithelial or stromal CD8 expression had shorter progression-free survival (PFS) than those with high intraepithelial or stromal CD8 expression, albeit not significantly. We clarified that the tumor immune microenvironment had an impact on clinicopathological features within the group with MMR loss, which is the main target for ICIs, limited to endometrioid carcinoma, G1. Further studies are needed, including on patients administered ICIs.
    DOI:  https://doi.org/10.1097/PGP.0000000000001020
  11. Cancer Sci. 2024 Feb 03.
    Beyond blood: Advancing the frontiers of liquid biopsy in oncology and personalized medicine.
    Ying Bao, Dejing Zhang, Huihui Guo, Wenxue Ma.
      Liquid biopsy is emerging as a pivotal tool in precision oncology, offering a noninvasive and comprehensive approach to cancer diagnostics and management. By harnessing biofluids such as blood, urine, saliva, cerebrospinal fluid, and pleural effusions, this technique profiles key biomarkers including circulating tumor DNA, circulating tumor cells, microRNAs, and extracellular vesicles. This review discusses the extended scope of liquid biopsy, highlighting its indispensable role in enhancing patient outcomes through early detection, continuous monitoring, and tailored therapy. While the advantages are notable, we also address the challenges, emphasizing the necessity for precision, cost-effectiveness, and standardized methodologies in its broader application. The future trajectory of liquid biopsy is set to expand its reach in personalized medicine, fueled by technological advancements and collaborative research.
    Keywords:  circulating tumor DNA (ctDNA); liquid biopsy; noninvasive cancer detection; personalized medicine; precision oncology
    DOI:  https://doi.org/10.1111/cas.16097
  12. Nat Rev Urol. 2024 Feb 02.
    The yin and yang of chromosomal instability in prostate cancer.
    Marc Carceles-Cordon, Jacob J Orme, Josep Domingo-Domenech, Veronica Rodriguez-Bravo.
      Metastatic prostate cancer remains an incurable lethal disease. Studies indicate that prostate cancer accumulates genomic changes during disease progression and displays the highest levels of chromosomal instability (CIN) across all types of metastatic tumours. CIN, which refers to ongoing chromosomal DNA gain or loss during mitosis, and derived aneuploidy, are known to be associated with increased tumour heterogeneity, metastasis and therapy resistance in many tumour types. Paradoxically, high CIN levels are also proposed to be detrimental to tumour cell survival, suggesting that cancer cells must develop adaptive mechanisms to ensure their survival. In the context of prostate cancer, studies indicate that CIN has a key role in disease progression and might also offer a therapeutic vulnerability that can be pharmacologically targeted. Thus, a comprehensive evaluation of the causes and consequences of CIN in prostate cancer, its contribution to aggressive advanced disease and a better understanding of the acquired CIN tolerance mechanisms can translate into new tumour classifications, biomarker development and therapeutic strategies.
    DOI:  https://doi.org/10.1038/s41585-023-00845-9
  13. Int J Gynecol Pathol. 2024 Feb 02.
    Does "One Size Fits All"? Rethinking FIGO Depth of Invasion Measurements in Vulvar Cancer.
    Maaike C G Bleeker, Tjalling Bosse, Koen K van de Vijver, Joost Bart, Hugo Horlings, Trudy G N Jonges, Nicole C M Visser, Loes F S Kooreman, Johan Bulten, Patricia C Ewing-Graham.
      Depth of invasion (DOI) is an important diagnostic parameter in patients with vulvar carcinoma, where a cutoff value of 1 mm largely determines the tumor stage and the need for groin surgery. DOI measurement should be reproducible and straightforward. In light of the new recommendation on how to measure DOI in the International Federation of Gynecology and Obstetrics (FIGO) staging system 2021, an exploratory study was conducted on the current practice of DOI measurement in vulvar cancer. In this study of 26 selected cases, 10 pathologists with high exposure to vulvar cancer cases in daily practice assessed both the conventional (FIGO 2009) and alternative (FIGO 2021) DOI methods for applicability and preference. In this set of cases, the DOI measurement according to FIGO 2009 was generally considered easier to apply than the measurement according to FIGO 2021, with applicability being rated as "easy to reasonable" in 76.9% versus 38.5% of cases, respectively (P=0.005). The preferred method was FIGO 2009 or tumor thickness in 14 cases and FIGO 2021 in 6 cases. No invasion was preferred in 1 case. For the remaining 5 cases, half of the pathologists opted for the FIGO 2009 method and half for the FIGO 2021 method. Although the FIGO 2009 method proved to be more readily applicable in most of the cases studied, the method may differ for each case. There may not be a "one size fits all" solution for all cases of vulvar cancer.
    DOI:  https://doi.org/10.1097/PGP.0000000000001009
  14. Elife. 2024 Jan 30. pii: RP92046. [Epub ahead of print]12
    Spatial transcriptomics and single-nucleus RNA sequencing reveal a transcriptomic atlas of adult human spinal cord.
    Donghang Zhang, Yali Chen, Yiyong Wei, Hongjun Chen, Yujie Wu, Lin Wu, Jin Li, Qiyang Ren, Changhong Miao, Tao Zhu, Jin Liu, Bowen Ke, Cheng Zhou.
      Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and neural diseases, the underlying organization of neuronal clusters and their spatial location remain elusive. Recently, several studies have attempted to define the neuronal types and functional heterogeneity in the spinal cord using single-cell or single-nucleus RNA sequencing in animal models or developing humans. However, molecular evidence of cellular heterogeneity in the adult human spinal cord is limited. Here, we classified spinal cord neurons into 21 subclusters and determined their distribution from nine human donors using single-nucleus RNA sequencing and spatial transcriptomics. Moreover, we compared the human findings with previously published single-nucleus data of the adult mouse spinal cord, which revealed an overall similarity in the neuronal composition of the spinal cord between the two species while simultaneously highlighting some degree of heterogeneity. Additionally, we examined the sex differences in the spinal neuronal subclusters. Several genes, such as SCN10A and HCN1, showed sex differences in motor neurons. Finally, we classified human dorsal root ganglia (DRG) neurons using spatial transcriptomics and explored the putative interactions between DRG and spinal cord neuronal subclusters. In summary, these results illustrate the complexity and diversity of spinal neurons in humans and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.
    Keywords:  DRG; human; neuronal clusters; neuroscience; single-nucleus RNA sequencing; spatial transcriptomics; spinal cord
    DOI:  https://doi.org/10.7554/eLife.92046
  15. Cell Oncol (Dordr). 2024 Jan 31.
    Omics-based molecular classifications empowering in precision oncology.
    Zhaokai Zhou, Ting Lin, Shuang Chen, Ge Zhang, Yudi Xu, Haijiao Zou, Aoyang Zhou, Yuyuan Zhang, Siyuan Weng, Xinwei Han, Zaoqu Liu.
       BACKGROUND: In the past decades, cancer enigmatical heterogeneity at distinct expression levels could interpret disparities in therapeutic response and prognosis. It built hindrances to precision medicine, a tactic to tailor customized treatment informed by the tumors' molecular profile. Single-omics analysis dissected the biological features associated with carcinogenesis to some extent but still failed to revolutionize cancer treatment as expected. Integrated omics analysis incorporated tumor biological networks from diverse layers and deciphered a holistic overview of cancer behaviors, yielding precise molecular classification to facilitate the evolution and refinement of precision medicine.
    CONCLUSION: This review outlined the biomarkers at multiple expression layers to tutor molecular classification and pinpoint tumor diagnosis, and explored the paradigm shift in precision therapy: from single- to multi-omics-based subtyping to optimize therapeutic regimens. Ultimately, we firmly believe that by parsing molecular characteristics, omics-based typing will be a powerful assistant for precision oncology.
    Keywords:  Clinical translation; Molecular classification; Omics biomarkers; Precision oncology
    DOI:  https://doi.org/10.1007/s13402-023-00912-8
  16. Mol Biol Rep. 2024 Jan 28. 51(1): 219
    Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy.
    Aasma Zafar, Muhammad Jawad Khan, Junaid Abu, Aisha Naeem.
      Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls of conventional anticancer therapies such as systematic toxicity, compromised life quality, and limited to severe side effects are major areas of concern of conventional cancer treatment approaches. Owing to the expansion of knowledge and technological advancements in the field of cancer biology, more innovative and safe anti-cancerous approaches such as immune therapy, gene therapy and targeted therapy are rapidly evolving with the aim to address the limitations of conventional therapies. The concept of immunotherapy began with the capability of coley toxins to stimulate toll-like receptors of immune cells to provoke an immune response against cancers. With an in-depth understating of the molecular mechanisms of carcinogenesis and their relationship to disease prognosis, molecular targeted therapy approaches, that inhibit or stimulate specific cancer-promoting or cancer-inhibitory molecules respectively, have offered promising outcomes. In this review, we evaluate the achievement and challenges of these technically advanced therapies with the aim of presenting the overall progress and perspective of each approach.
    Keywords:  Gene therapy; Immunotherapy; Targeted molecular therapy
    DOI:  https://doi.org/10.1007/s11033-023-09096-8
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