Rebecca Previs’ Post

Exciting Research Update on Pancreatic Ductal Adenocarcinoma (PDAC)! I'm thrilled to share our latest preprint on bioRxiv, where we explore a promising combination therapy for PDAC, a cancer notorious for its resistance to current chemotherapies. Our study tackles the challenge of personalized therapy in PDAC by focusing on tumors dependent on KRAS for survival (dKRAS). We discovered that gene expression signature scores can effectively assess KRAS dependency, opening doors to tailored treatments. Findings: KRAS Dependency: Nearly 90% of PDAC cases harbor KRAS mutations. Our transcriptomic-based KRAS dependency scores can predict the efficacy of targeted therapies. Combination Therapy: We found that combining low-dose decitabine (DEC) with the PARP inhibitor olaparib (OLA) significantly enhances antitumor activity in dKRAS-PDAC. This synergy is due to DEC inducing DNA damage and activating a DNA damage response, which is further exploited by inhibiting PARP with OLA. Broader Efficacy: This combination is effective even in BRCA1/2 wild-type and homologous recombination-proficient tumors, extending the clinical benefit of OLA beyond BRCA status. Metastasis Inhibition: In dKRAS-PDAC tumors with a BRCA2 mutation, DEC+OLA inhibited metastasis growth, outperforming single-drug treatments. These findings underscore the potential of DEC+OLA combination therapy in PDAC, highlighting DNA damage response as a critical mechanism and advocating for its clinical evaluation irrespective of BRCA1/2 status. Read the full preprint here: https://lnkd.in/dTsM8kri Thank you to my incredible team and collaborators for contributing to this research. We believe this approach could pave the way for more effective and personalized treatments for PDAC patients. #PancreaticCancer #PDAC #KRAS #CancerResearch #PersonalizedMedicine #bioRxiv #Research #Oncology #CancerTherapy

After more than a decade of waiting since the most recent FDA authorization in the indication, Adaptimmune has triumphantly crossed the finish line with FDA accelerated approval of TECELRA® (afamitresgene autoleucel, “afami-cel”) for adult patients with unresectable or metastatic synovial sarcoma. This innovative autologous engineered TCR T cell therapy targets the MAGE-A4 protein, prevalent in many cases of this rare, aggressive, and difficult-to-treat soft tissue solid tumor. CDx biomarker tests for HLA type and MAGE-A4 tumor expression will be required prior to treatment with TECELRA. The FDA’s nod follows compelling results from cohort 1 of the SPEARHEAD-1 trial, involving 44 patients with advanced unresectable or metastatic synovial sarcoma who had previously undergone at least one line of anthracycline or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 10^9–10·0 × 10^9 T cells) after lymphodepletion. The primary endpoint, overall response rate (ORR), was assessed by an independent review committee using RECIST v1.1 in the modified intention-to-treat population. The results? An ORR of 43%, with a median response duration of 6 months, and 39% of responsive patients maintaining their response for over a year. Having witnessed firsthand the damage that synovial sarcomas can provoke on their surrounding tissues in my past life as a histotech, I am overjoyed to see this FDA approval of a cell therapy product arrive at a time when solid tumor treatments have lagged significantly behind those for their liquid tumor counterparts. Progress! This achievement is a testament to the relentless dedication of patients, caregivers, healthcare providers, and countless indefatigable cell and gene therapy professionals who have collectively brought this therapy to fruition. It’s a banner day for the field of cell and gene therapy and I’m proud to be in it. #celltherapy #cellandgenetherapy #TCR #TCells #solidtumors #sarcoma #celltherapymanufacturing #CGT #biomarkers #CDx #regulatoryaffairs https://lnkd.in/gCyYa4rY

In collaboration with Gerry Melino and our partners at University of Rome Tor Vergata, our newest publication has been released in Discover Oncology. Hepatocellular carcinoma (HCC) is a primary liver cancer that often develops resistance to chemotherapy, a phenomenon known as chemoresistance. Powered by the Indivumed Therapeutics Omics Hub, “Genomic and transcriptomic profiling of hepatocellular carcinoma reveals a rare molecular subtype” demonstrates that multi-omics approaches can enable a better understanding of complex cellular and molecular changes, offering a more complete picture of the cancer disease. This could potentially lead to the development of new strategies to predict, prevent, or overcome chemoresistance, improving the effectiveness of HCC treatment. View the full publication: https://lnkd.in/efSMHMge

https://lnkd.in/gbdeS3RE As important a paper, in Journal of Clinical Oncology, in recent years in the field of #ocularoncology and #ocularmelanoma was just brought forth by the Collaborative Ocular Oncology Group, lead by J William Harbour, MD at UT Southwestern. A multi-country effort that has now validated gene expression profiling as well as PRAME, as a risk modifier, in a very clinically relevant patient population. With over 1500 patients followed for over 42 months, a new 4 group stratification predicts melanoma-specific survival at 98.8% for the lowest risk compared to 61% for the highest risk groups. This information will inform clinicians, patients, and - most importantly- clinical trial entry into the future. National Cancer Institute (NCI), Castle Biosciences, Inc.Byers Eye Institute at Stanford, American Society of Clinical Oncology (ASCO), Journal of Clinical Oncology, Zelia Correa, Amy Schefler, Miguel Materin, Thomas Aaberg Jr, Alison Skillet, Ezekiel Weis, Ivana Kim, Scott Walter, Brian Marr, Basil Williams, Scott Oliver, James Dollar, Song Zhang, Tony Tsai, David Reichstein, @eugene Shildkrot, @devron char, Demirci Hakan, @Cameron javid, @dan gomobos, JayPeter Hovland, Christina D.,

The Impact of Prior Single-Gene Testing on Comprehensive Genomic Profiling Results for Patients with Non-Small Cell Lung Cancer:-

🌟Exciting News in Breast Cancer Diagnostics! 🌟 We are thrilled to announce the latest update to the German Uniform Evaluation Standard (EBM) catalogue for the third quarter of 2024, which includes the introduction of a groundbreaking new code, 19466. This code represents a significant advancement in the fight against breast cancer. Code 19466 allows for the targeted determination of ESR1 mutations using circulating tumour #DNA. This test is crucial for postmenopausal women and men with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer. It provides a targeted treatment pathway for those whose disease has progressed after at least one line of endocrine therapy, including a CDK 4/6 inhibitor. 🧬 Why is this important? This new code covers the detection of activating mutations E380Q, L536H, Y537C/N/S, and D538G, along with up to four additional activating mutations in the ligand binding domain using PCR-based methods. This precision in detecting mutations ensures that patients receive the most effective, tailored treatment possible, enhancing their chances of positive outcomes. 💰 Tariff and Billing: The tariff for this test is set at €250.61 and can be billed twice if the disease persists. This makes the test not only a scientific breakthrough but also a financially viable option for ongoing patient management. 🔬 Manufactured by: This innovative diagnostic test is developed by QuantideX qPCR ESR1 Mutation Kita leader in precision medicine and diagnostic solutions. Their commitment to advancing healthcare and improving patient outcomes is evident in the introduction of this essential diagnostic tool. By integrating Code 19466 into the #EBM catalogue, Germany is taking a decisive step towards enhancing personalised medicine and providing hope to many battling #breastcancer. This development underscores the importance of continued investment in medical research and the swift adaptation of new technologies into clinical practice. #BreastCancerAwareness #MedicalInnovation #Healthcare #Diagnostics #PrecisionMedicine #Oncology #EBMUpdate #Germany #CancerTreatment #PersonalizedMedicine #HealthcareInnovation www.asuragen.com

Cancer is by its very nature a very personal disease of each patients genome. It therefore makes perfect sense to identify and quantitate the cancer originating DNA fragments floating freely in every patients blood stream before interventional treatment AND after. By anchoring this measurement for each patients individually, a significant relative reduction in this circulating tumor DNA (ctDNA) tumor fraction is a welcome sign that the treatment has achieved initial success and bodes well for longer term remission. That is what Tempus AI xM Monitor can achieve for patients. For pharma companies, the same relative reduction of ctDNA tumor fraction (observed during a clinical trial across the patients in a treatment group), can provide an early sign that their experimental regiment is likely working.

Source: Journal of pharmaceutical and biomedical analysis A study found distinct differences in the plasma molecular profiles of early-onset and late-onset colorectal cancer patients. Using metabolomics and lipidomics analyses, the study identified specific metabolites and lipids that were altered in the colorectal cancer group. The analysis also revealed that early-onset colorectal cancer patients had unique metabolomic and lipidomic profiles compared to late-onset patients. Gene expression data further supported these distinctions. The findings provide insights into the development mechanisms of early-onset colorectal cancer and potential plasma biomarkers for diagnosis.

The SOLTI-1402 CORALEEN phase II study revealed that neoadjuvant treatment with #letrozole and #ribociclib in high-risk early stage Luminal B breast cancer patients resulted in molecular downstaging, as evidenced by a substantial degree of intrinsic subtype conversion to Luminal A and a decrease in Ki67 immunohistochemistry expression. Both therapies resulted in a decrease in Ki67 and an increase in cell cycle arrest (CCCA); however, the mechanisms through which CCCA was achieved differed between the ribociclib and letrozole arm and the chemotherapy arm. Gene expression analysis indicated that the combination of ribociclib and letrozole did not demonstrate enrichment in cell populations with tumor-initiating properties, unlike traditional cytotoxic chemotherapy and letrozole monotherapy. The study found that changes in TIL (Tumor Infiltrating Lymphocytes) quantification may not be a reliable marker of response or as a comprehensive indicator of immune microenvironment change in the Luminal B population. Gene expression signatures associated with antigen-presenting cells showed increased expression in CCCA tumors post-chemotherapy, while the same modules displayed decreased expression after ribociclib and letrozole treatment. #cancerresearch #drugdiscovery #clinicalresearch https://lnkd.in/eH38xTsT

Burning Rock Dx Spotlight: OncoScreen®Plus A study explored tumor-immune Microenvironment and NRF2 Associate with Clinical Efficacy of PD-1 Blockade Combined with Chemotherapy in Lung Squamous Cell Carcinoma. OncoScreen®Plus was been used to assess the Genomic profiling and tumor mutational burden (TMB). Result： As an immune signature, the immune-related gene expression signature (GES) might identify LUSC patients likely to benefit from first-line tislelizumab plus chemotherapy. Highlights: 1) Tislelizumab plus chemotherapy prolongs PFS in lung squamous cell cancer 2) An 11-gene immune gene expression signature correlates with the PFS benefit 3) In contrast, the PFS benefit is observed regardless of PD-L1 expression or TMB 4) NRF2 pathway activation negatively impacts predictive potential of PD-L1 and TMB Read the full study: https://lnkd.in/gntM7_BD #NSCLC #TMB #BurningRockDx #OncoScreen®Plus