bims-preonc Biomed News
on Precision oncology
Issue of 2024–09–29
twelve papers selected by
Ankita Daiya, OneCell Diagnostics Inc.
  1. Clinical bioinformatics desiderata for molecular tumor boards.
  2. Precision oncology in patients with breast cancer: towards a 'screen and characterize' approach.
  3. Pharmacomicrobiomics in precision cancer therapy: bench to bedside.
  4. An Evolving Landscape: New Therapies for Metastatic Colorectal Cancer.
  5. Development of transcriptomic tools for predicting the response to individual drug of the mFOLFIRINOX regimen in patients with metastatic pancreatic cancer.
  6. The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology.
  7. Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.
  8. Efficacy of different medications in the treatment of gynaecological tumours: a clinical meta-analysis.
  9. Current Practices in Genetic Testing for Prostate Cancer: The Indian Scenario.
  10. ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer.
  11. Application of machine learning for predicting lymph node metastasis in T1 colorectal cancer: a systematic review and meta-analysis.
  12. Personalized treatment approach for HER2-positive metastatic breast cancer.
  1. Brief Bioinform. 2024 Jul 25. pii: bbae447. [Epub ahead of print]25(5):
    Clinical bioinformatics desiderata for molecular tumor boards.
    Matteo Pallocca, Martina Betti, Sara Baldinelli, Ramona Palombo, Gabriele Bucci, Luca Mazzarella, Giovanni Tonon, Gennaro Ciliberto.
      Clinical Bioinformatics is a knowledge framework required to interpret data of medical interest via computational methods. This area became of dramatic importance in precision oncology, fueled by cancer genomic profiling: most definitions of Molecular Tumor Boards require the presence of bioinformaticians. However, all available literature remained rather vague on what are the specific needs in terms of digital tools and expertise to tackle and interpret genomics data to assign novel targeted or biomarker-driven targeted therapies to cancer patients. To fill this gap, in this article, we present a catalog of software families and human skills required for the tumor board bioinformatician, with specific examples of real-world applications associated with each element presented.
    Keywords:  biobanking; clinical bioinformatics; clinical informatics; data engineering; decision support tools; molecular tumor board; molecular tumor registry; variant actionability; variant annotation
    DOI:  https://doi.org/10.1093/bib/bbae447
  2. ESMO Open. 2024 Sep 19. pii: S2059-7029(24)01486-8. [Epub ahead of print]9(10): 103716
    Precision oncology in patients with breast cancer: towards a 'screen and characterize' approach.
    E Rassy, M F Mosele, A Di Meglio, B Pistilli, F Andre.
      
    DOI:  https://doi.org/10.1016/j.esmoop.2024.103716
  3. Front Immunol. 2024 ;15 1428420
    Pharmacomicrobiomics in precision cancer therapy: bench to bedside.
    Khanh Le Ngoc, Tran Thu Ha Pham, Tiep Khac Nguyen, Phung Thanh Huong.
      The burgeoning field of pharmacomicrobiomics offers promising insights into the intricate interplay between the microbiome and cancer, shaping responses to diverse treatment modalities. This review aims to analyze the molecular mechanisms underlying interactions between distinct microbiota types and cancer, as well as their influence on treatment outcomes. We explore how the microbiome impacts antitumor immunity, and response to chemotherapy, immunotherapy, and radiation therapy, unveiling its multifaceted roles in cancer progression and therapy resistance. Moreover, we discuss the challenges hindering the development of microbiome-based interventions in cancer therapy, including standardization, validation, and clinical translation. By synthesizing clinical evidence, we underscore the transformative potential of harnessing pharmacomicrobiomics in guiding cancer treatment decisions, paving the way for improved patient outcomes in clinical practice.
    Keywords:  cancer therapy; microbiome intervention; microbiota; pharmacomicrobiome; precision medicine
    DOI:  https://doi.org/10.3389/fimmu.2024.1428420
  4. Clin Colorectal Cancer. 2024 Aug 24. pii: S1533-0028(24)00076-8. [Epub ahead of print]
    An Evolving Landscape: New Therapies for Metastatic Colorectal Cancer.
    Christiana Mo, Bhawneet Chadha, Chaoyuan Kuang.
      Substantial progress is being made in the development of novel therapies directed against colorectal cancer. The discovery of various molecular markers and advances in tumor profiling have facilitated the development of new targeted agents and immunotherapy. Not only have these drugs improved progression-free survival and even overall survival in some cases, but their related outcomes have also raised questions as to how to best combine or sequence therapies for even greater efficacy. Furthermore, we are beginning to understand how these combination therapies may yield for greater therapeutic response for patients with microsatellite stable colorectal cancer for which there is much need for improvement. In this article, we review recent trial data and explore the outcomes of various targeted therapies and immunotherapies for patient with advanced colorectal cancer.
    Keywords:  Chemotherapy; Clinical trials; Colorectal cancer; Immunotherapy; Targeted therapy
    DOI:  https://doi.org/10.1016/j.clcc.2024.08.003
  5. Front Oncol. 2024 ;14 1437200
    Development of transcriptomic tools for predicting the response to individual drug of the mFOLFIRINOX regimen in patients with metastatic pancreatic cancer.
    Nicolas Fraunhoffer, Carlos Teyssedou, Patrick Pessaux, Martin Bigonnet, Nelson Dusetti, Juan Iovanna.
       Background: The utilization of modified FOLFIRINOX (mFFX) therapy has shown notable advancements in patient outcomes in both localized and metastatic PDAC. Nevertheless, the effectiveness of mFFX treatment comes at the cost of elevated toxicity, leading to its restriction to patients with adequate performance status. Consequently, the administration of mFFX is contingent upon patient performance rather than rational criteria. The ideal scenario would involve the ability to assess the sensitivity of each drug within the mFFX regimen, minimizing unnecessary toxicity without compromising clinical benefits.
    Methods: We developed transcriptomic signatures for each drug of the mFFX regimen (5FU, oxaliplatin and irinotecan) by integrating transcriptomic data from PDC, PDO and PDX with their corresponding chemo-response profiles to capture the biological components responsible for the response to each drug. We further validated the signatures in a cohort of 167 patients with advanced and metastatic PDAC.
    Results: All three signatures captured high responder patients for OS and PFS in the mFFX arm exclusively. We then studied the response of patients to 0, 1, 2 and 3 drugs and we identified a positive correlation between the number of drugs predicted as sensitive and the OS and PFS, and the with objective response rate.
    Conclusions: We developed three novel transcriptome-based signatures which define sensitivity for each mFFX components that can be used to rationalize the administration of the mFFX regimen in patients with metastatic pancreatic cancer and could help to avoid unnecessary toxic effects.
    Keywords:  FOLFIRINOX; RNA signatures; chemosensitivity prediction; metastatic cancer; pancreatic cancer; precision medicine
    DOI:  https://doi.org/10.3389/fonc.2024.1437200
  6. Med Oncol. 2024 Sep 24. 41(11): 250
    The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology.
    Mark P van Opijnen, Filip Y F de Vos, Edwin Cuppen, Marjolein Geurts, Sybren L N Maas, Marike L D Broekman.
      For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.
    Keywords:  Clinical trial; Genome-driven oncology; Molecular testing; Recurrent glioblastoma; Targeted treatment
    DOI:  https://doi.org/10.1007/s12032-024-02501-7
  7. Nat Med. 2024 Sep 23.
    Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.
    Scott Kopetz, Danielle A Murphy, Jie Pu, Fortunato Ciardiello, Jayesh Desai, Eric Van Cutsem, Harpreet Singh Wasan, Takayuki Yoshino, Hedieh Saffari, Xiaosong Zhang, Phineas Hamilton, Tao Xie, Rona Yaeger, Josep Tabernero.
      The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance. In this prespecified, exploratory biomarker analysis of the BEACON CRC study, we characterize genomic and transcriptomic correlates of clinical outcomes and acquired resistance mechanisms through integrated clinical and molecular analysis, including whole-exome and -transcriptome tissue sequencing and circulating tumor DNA genomic profiling. Tumors with higher immune signatures showed a trend towards increased OS benefit with Enco+Bini+Cetux. RAS, MAP2K1 and MET alterations were most commonly acquired with Enco+Cetux±Bini, and more frequent in patients with a high baseline cell-cycle gene signature; baseline TP53 mutation was associated with acquired MET amplification. Acquired mutations were subclonal and polyclonal, with evidence of increased tumor mutation rate with Enco+Cetux±Bini and mutational signatures (SBS17a/b). These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224.
    DOI:  https://doi.org/10.1038/s41591-024-03235-9
  8. Front Oncol. 2024 ;14 1428937
    Efficacy of different medications in the treatment of gynaecological tumours: a clinical meta-analysis.
    Qiaoying Chen.
       Background: A gynaecological tumour is one of the world's leading causes of death for women globally. Among women, cancer is the 8th most common cause of death. Since there are no such programmes, the majority of women who are diagnosed with the condition are either in advanced stages or do not respond well to current treatments. Even if patients react to the treatments, they still risk having the cancer return, at which point any further medical intervention is met with resistance.
    Method: For this study, we selected the systemic reviews and articles that have the use of different medications used for the treatment of gynaecological tumours.
    Results: Regarding metformin use, this study found a positive relationship between higher survival and metformin use. Five of the studies that examined the use of statins revealed a link between statin use and higher overall and/or progression-free survival rates. Individuals on lipophilic and hydrophilic statins would do better. Research evaluating beta-blocker use during neoadjuvant treatment revealed a time-varying effect, with improved survival seen across all users early in the follow-up period. However, only non-selective beta-blocker users demonstrated a correlation with higher survival after five years. One study found that the benefits of aspirin use were significant, but the advantage for continuous users (both before and after diagnosis) was minimal.
    Conclusion: Conclusions on the association between gynaecological tumour survival and NA-NSAIDs, metformin, beta-blockers, and aspirin cannot be drawn due to insufficient evidence. However, the vast majority of statin studies have demonstrated that users had higher rates of survival. Bias, however, bias may affect the results of the studies.
    Keywords:  drug therapy; gynaecologic neoplasms; metformin; non-steroidal anti-inflammatory agents (NSAIDs); survival rate
    DOI:  https://doi.org/10.3389/fonc.2024.1428937
  9. Indian J Public Health. 2024 Jul 01. 68(3): 396-400
    Current Practices in Genetic Testing for Prostate Cancer: The Indian Scenario.
    Ganesh Bakshi, Senthil Rajappa, Amit Joshi, Chirag Desai, Sanjai Addla, Hemang Baxi, Vineet Talwar, Prabrajya Narayan Mohapatra, Shivam Shingla, Utkarsha Kulkarni.
       BACKGROUND: Despite genetic testing being recommended by international guidelines for the selection of targeted therapy for prostate cancer (PCa), limited data are available on genetic testing for PCa in India.
    OBJECTIVES: The objective is to understand the current genetic testing practice pattern for PCa in India.
    MATERIALS AND METHODS: A panel of 9 experts developed and validated a premeeting online questionnaire comprising 12 objective questions. The questionnaire was circulated from February 2022 to May 2022 among medical oncologists and uro-oncologists across pan-India, followed by response collection over 3 months. Descriptive statistics were used to summarize results and concluding statements were formulated on current genetic testing practice patterns for PCa.
    RESULTS: A total of 103 responses were received. Genetic testing was advised by 35.9% of the participants in <5% of patients with PCa. Patients with a family history of PCa (88.3%) were most commonly referred for genetic testing. Nearly half (50.2%) of the participants routinely tested for homologous recombination repair (HRR) genes; 52% used blood and tissue as the most preferred specimen for performing genetic testing and 44.7% followed the testing sequence of tumor tissue followed by blood. Major barriers to genetic testing were affordability and scarcity of genetic counselors, while a major change could be brought by making it cost-effective and improving access to medication.
    CONCLUSIONS: We observed a lower prescription frequency of genetic testing for the HRR gene across pan-India. Improving the quality and access to genetic testing and the availability of cost-effective-targeted therapies will aid in delivering personalized care to patients with metastatic PCa.
    DOI:  https://doi.org/10.4103/ijph.ijph_686_23
  10. J Cancer Res Clin Oncol. 2024 Sep 22. 150(9): 428
    ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer.
    Florian Bürtin, Liema Elias, Sebastian Hinz, Michael Forster, Guido Hildebrandt, Bernd Frerker, Felix Bock.
       BACKGROUND: Liquid biopsy is a minimally invasive procedure investigating tumor mutations.
    METHODS: In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery. Response was assessed by Dworak. Liquid biopsies were taken before and immediately after neoadjuvant radiotherapy to isolate and ultradeeply sequence cell free DNA with a panel of 127 genes. Somatic mutations were determined bioinformatically by comparison with normal DNA from leukocytes to distinguish them from germline variants or aging mutations.
    RESULTS: In 12 patients (71%) at least one somatic mutation was detected. In 8/12 patients a decrease and in 4/12 an increase or mixed response in ctDNA was seen. Statistical correlation between ctDNA analysis and clinical response could not be seen.
    CONCLUSION: ctDNA is responding to neoadjuvant therapy and liquid biopsy is easily integrated into a daily routine. As part of translational research this protocol leaves room for further investigations.
    Keywords:  Liquid biopsy; Locally advanced rectal cancer; Neoadjuvant therapy; Radiotherapy; ctDNA
    DOI:  https://doi.org/10.1007/s00432-024-05944-7
  11. Langenbecks Arch Surg. 2024 Sep 23. 409(1): 287
    Application of machine learning for predicting lymph node metastasis in T1 colorectal cancer: a systematic review and meta-analysis.
    Chinock Cheong, Na Won Kim, Hye Sun Lee, Jeonghyun Kang.
       BACKGROUND: We review and analyze research on the application of machine learning (ML) and deep learning (DL) models to lymph node metastasis (LNM) prediction in patients with T1 colorectal cancer (CRC). Predicting LNM before radical surgery is important in patients with T1 CRC. However, current surgical treatment guidelines are limited. LNM prediction using ML or DL may improve predictive accuracy. The diagnostic accuracy of LNM prediction using ML- and DL-based models for patients with CRC was assessed.
    METHODS: We performed a comprehensive search of the PubMed, Embase, and Cochrane databases (inception to April 30th of 2022) for studies that applied ML or DL to LNM prediction in T1 CRC patients specifically to compare with histopathological findings and not related to radiological aspects.
    RESULTS: 33,199 T1 CRC patients enrolled across seven studies with a retrospective design were included. LNM was observed in 3,173 (9.6%) patients. Overall, the ML- and DL-based model exhibited a sensitivity of 0.944 and specificity of 0.877 for the prediction of LNM in patients with T1 CRC. Six different types of ML and DL models were used across the studies included in this meta-analysis. Therefore, a high degree of heterogeneity was observed.
    CONCLUSIONS: The ML and DL models provided high sensitivity and specificity for predicting LNM in patients with T1 CRC, and the heterogeneity between studies was significant. These results suggest the potential of ML or DL as diagnostic tools. However, more reliable algorithms should be developed for predicting LNM before surgery in patients with T1 CRC.
    Keywords:  Deep learning; Lymph node metastasis; Machine learning; Risk factor; T1 colorectal cancer
    DOI:  https://doi.org/10.1007/s00423-024-03476-9
  12. Med Oncol. 2024 Sep 25. 41(11): 252
    Personalized treatment approach for HER2-positive metastatic breast cancer.
    Prashant Pandey, Rishabh Chaudhary, Devika Tripathi, Kousalya Lavudi, Kamal Dua, Michael Weinfeld, Afsaneh Lavasanifar, P S Rajinikanth.
      Breast cancer (BC) is a leading global concern for women, with 30% being HER2-positive cases linked to poorer outcomes. Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Although these therapies have improved MBC management and patient outcomes, resistance can develop, reducing effectiveness. Personalized strategies based on tumor characteristics offer hope for better responses and longer outcomes. This review outlines insights into MBC patients responding well to anti-HER2 treatments, even across multiple treatment regimen. Recent immunotherapy, locoregional therapy, and liquid biopsy breakthroughs are covered, suggesting ways to increase long-term responders. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics.
    Keywords:  Anti-HER2; Breast cancer; HER2; Immunotherapy; Liquid biopsy; Locoregional
    DOI:  https://doi.org/10.1007/s12032-024-02504-4
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