Mayank singh’s Post

Our research provides crucial insights into pancreatic ductal adenocarcinoma (PDAC). Hypoxia, a defining characteristic of PDAC, correlates with disease severity, influencing treatment response, invasiveness, and immunosuppression. Utilizing the Buffa gene signature, we pinpointed LGALS3 as a pivotal gene linked to high hypoxia levels. Elevated hypoxia is associated with reduced levels of T cells, NK cells, and dendritic cells, along with increased immunosuppressive molecules. These findings propose innovative strategies for advancing PDAC immunotherapy by targeting both hypoxia and specific immune elements. Kudos to the team's exceptional work, particularly acknowledging Hassan Sadozai's contributions. https://lnkd.in/es9rQuXv #pancreaticcancer #immunology #immunotherapy #teamcollaboration #teameffort #cancertreatment #cancerresearch #medicaladvancements #transcriptomics #collaborations #interdisciplinary #leadership #leadershipdevelopment #machinelearning

In their recent article for Cell & Gene, Sanofi's Sarah Cooley and Kyle Jensen explain the potential advantages of NK cell engagers (NKCEs), a novel class of multifunctional biologics, which have emerged as an exciting innate immune-based mechanism in #oncology research. #nkcells #immunotherapy #cartcelltherapy #cellandgenetherapy #cgt #NKCE https://lnkd.in/e7NRuNTM

Zhang, D., Wang, M., Ma, S. et al. Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages. Cancer Gene Ther (2024). https://lnkd.in/dAiqxzsJ "Abstract Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC."

From 2023 Annual American Society of Hematology (ASH) Meeting: Revolutionizing Hematologic Cancer Treatment with Groundbreaking T-Cell Therapy Exciting developments in cellular therapy are redefining treatment for challenging hematologic malignancies. Here's what's new: Targeting Aggressive Cancers: Innovative T-cell therapies target neoantigens from p53 and Ras mutations in cancers like AML and multiple myeloma. Preclinical Success: Experiments show that genetically engineered T cells can effectively target and eliminate cancer cells, offering new hope in treating resistant malignancies. Towards Clinical Trials: Building on these preclinical successes, upcoming clinical trials will explore the potential of these targeted T-cell therapies in patients. This groundbreaking approach opens new doors in cancer therapy, promising more effective treatments for those with high-risk hematologic cancers. #CancerResearch #CellTherapy #Hematology https://lnkd.in/gTE7iaxK

Read this recent Nat. Med. article to discover how researchers at MGH, Harvard, MIT, and USCF used Bio-Techne reagents to generate colorectal tumor organoids from BRAF V600E CRC patients to identify a correlation between MAPK suppression and immune gene induction in tumor cells. #organoids #colorectalcancer #cancerresearch https://bit.ly/3QCaoNZ

There is a small percentage of certain cancers where the cells start to lose their identity..and seem to take on the identity of other cells. So how does this happen? Well…researchers are still trying to tease apart the mechanisms, but have found a few answers…which are leading to more questions. About 25 years ago, researchers at Cold Spring Harbor Labs ‘discovered’ that a gene (p63) was important not only for the formation of normal basal cells (the small cells in the lower part of the epidermis), but also that this protein cased pancreatic cancer cells to become more basal-like. Fast-forward to today…and researchers are building on that research foundation. Now, p63 is a difficult protein to target with drugs, so they needed a different method of trying to ‘screen’ how p63 helped cells turn from ‘normal’ to basal-like. What they did—they screened the genomes of basal-like cancer cells and then ranked the genes needed to help these cells maintain their new identity. The top protein: MED12. MED12 is a subunit of the mediator complex—which is responsible for transcription regulation. In addition, they showed that MED12 & p63 could bind directly to each other…raising the question if both are needed to ‘switch’ cells to the basal-like? More research is needed…especially considering the mediator complex is essential for normal cellular activity—but if the interaction between the two could be disrupted? Also…more research is needed to see if there are other proteins that also play a part in switching the ‘identity’ of cells from their normal to ‘basal-like’. #cancerresearch #proteins #proteinproteininteractions #transcriptionalcontrol #mediatorcomplex

Jason Loveridge, our CEO, gave his view on what the future of cancer therapy will look like in Labiotech.eu’s recent article.    With #precisionmedicine gaining traction, #gene editing technologies such as #CRISPR “may play a role in cancer therapy by editing and repairing faulty genes linked to #cancer. With further research and refinement, gene editing could offer targeted treatments or cures for specific types of cancer” in the future.   Read this fantastic article in full here: https://bit.ly/3usySBW

A concise summary of what is going on, the major concerns and what is at stake in cancer immunotherapy, including Checkpoint Inhibitors, vaccines, ADC, CAR-T and gene editing. https://lnkd.in/ePHjNP-A

Researchers are investigating a subtype of breast cancer known as estrogen receptor-alpha positive (ER+). Gene fusions, where genes combine in unusual ways, may play a role in its progression. A neoplastic fusion transcript called RAD51AP1-DYRK4 was found in this cancer type, suggesting it is aggressive. A MEK inhibitor may be able to block this fusion-driven pathway and offer treatment options for recurrent and aggressive breast cancer cases. Source: https://lnkd.in/enBkN2Pj #medicalscience #genetherapy #breastcancer #lifescience #biology 

ENIGMA CHEK2gether Project: A comprehensive study aimed to address the clinical implications of missense variants in the CHEK2 gene, which are associated with a moderately increased risk of breast cancer. The researchers analyzed 460 missense variants identified by the ENIGMA consortium across 15 countries, employing functional assays to categorize them as functionally impaired, intermediate, or wild-type-like. Among the successfully analyzed variants, carriers of functionally impaired ones exhibited a moderate breast cancer risk similar to truncating CHEK2 variants, while carriers of wild-type/intermediate variants showed no clinically relevant risk. This comprehensive functional characterization sheds light on the significance of CHEK2 missense variants in breast cancer susceptibility, providing valuable insights for germline genetic testing. #germline #CHEK2