Giuseppe Giannini’s Post

A recent study highlighted the growing importance of personalized medicine in cancer treatment. It found that drugs tested in personalized trials for NSCLC showed a greater improvement in progression-free survival (PFS). However, the impact on overall survival (OS) is more complex, and the authors rightly point out that newer drug mechanisms might require longer follow-up to see a benefit in OS. This emphasizes the need for ongoing research alongside personalized treatment approaches.  Further studies exploring biomarkers beyond just tumor mutations, like tumor microenvironment or immune cell infiltration, could be key to unlocking even greater benefits for patients. Read more from Nature Portfolio here: https://lnkd.in/eiiU4AVx #CancerResearch #PrecisionMedicine

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers 1. NAD+ = rechargeable battery of biological systems. 2. There are three pathways of NAD+ biosynthesis. 1) Kynureine pathway: de novo synthesis of NAD+ from Tryptophan 2) Preiss-Handler pathway: NAPRT has a main role to make NAD+ from nicotinic acid. 3) Salvage pathway: NAMPT is a key enzyme to make NAD+ from nicotinamide. 3. Cancer cells utilize all pathways to meet their energy demand. 4. Therefore, NAMPT has been considered as a promising target for cancer therapy. 5. Fan groups of ShanghaiTech University have developed a next-generation PROTAC to degrade NAMPT. 6. Treatment with the lead PROTAC and nicotinic acid is efficacious against NAPRT-deficient pan-cancers. Because normal cells retain NAPRT activity and can utilize nicotinic acid, the toxicity of NAMPT-targeting PROTACs is mitigated. https://lnkd.in/ghGQGCr3

This is a new review article published in Antibody Therapeutics (2022 CiteScore: 6.4). The research on ADCs is advancing toward an innovative transitional phase. Small antibody fragments or other structurally derived scaffolds from natural proteins have been employed for the development of ADCs, aiming to overcome the limitations of traditional ADCs and enhance their therapeutic effects in solid tumor treatment. This review is focused upon current advancements in novel ADC development utilizing smaller antibody formats from ∼6 to 80kDa, with particular emphasis on single-domain antibodies, which have been widely applied in novel ADC design. Additionally, strategies to optimize clinical translation are discussed, including half-life extension, acceleration of internalization, and reduction of immunogenic potential. The corresponding author is Dr. Yanling Wu at Fudan University in China. Antibody Therapeutics is the official journal of Chinese Antibody Society (CAS), published by Oxford University Press. CAS’s 2024 Annual Conference will take place in Cambridge, MA, USA, on Saturday, May 11, 2024. You are welcome to register for the conference right NOW via the following link. https://lnkd.in/ecmFPA4v

"Several types of conventional cancer therapies, such as radiotherapy or chemotherapy, destroy healthy cells along with cancer cells. In advanced stages of cancer, tissue loss from treatments can be substantial and even fatal. Cutting-edge cancer therapies that employ nanoparticles can specifically target cancer cells, sparing healthy tissue. Recent studies have demonstrated that plant-derived nanoparticles (pdNPs) that have therapeutic effects can be an effective alternative to traditional cancer treatments. However, no pdNPs have been approved as anticancer therapeutic agents till date. Rice bran is a byproduct generated during rice refining process that has limited utility and low commercial value. However, it contains several compounds with anticancer properties, such as γ-oryzanol and γ-tocotrienol." #cancertreatment #cancer #oncology

It's always amazing to see innovative, groundbreaking research in the field of cancer treatments and research. As outlined here, the "protein sandwich" technique is offering promising prospects for advancing cancer treatment modalities. Using an “intramolecular bivalent glue” researchers were able to bind together proteins that would otherwise fall apart. This has been crucial in creating more comprehensive, holistic drug development and therapeutic interventions. I’m interested to see if these new class of drugs, called “intramolecular bivalent glue,”, will be successful in creating drugs for different diseases. #CancerResearch #MedicalInnovation #ProteinTherapeutics #proteindegraders

🔇 Announcing the latest publication from ACS Publications, and the JAMCDD Journal: Discovery of Pyridine-2-Carboxamides Derivatives as Potent and Selective HPK1 Inhibitors for the Treatment of Cancer Abstract: Hematopoietic progenitor kinase 1 (HPK1) has emerged as an attractive target for immunotherapy due to its critical role in T cell activation and proliferation. The major challenge in developing HPK1 inhibitors lies in balancing kinase selectivity, pharmacokinetic (PK) properties, and therapeutic efficacy. In this study, we report a series of pyridine-2-carboxamide analogues demonstrating strong HPK1 inhibitory activity in enzymatic and cellular assays, along with good kinase selectivity. Among these analogues, compound 19 showed good in vitro HPK1 inhibitory activity, excellent kinase selectivity (>637-fold vs GCK-like kinase and >1022-fold vs LCK), and robust in vivo efficacy in the CT26 (tumor growth inhibition (TGI) = 94.3%, 2/6 CRs) and MC38 murine colorectal cancer models (TGI = 83.3%, 1/6 complete response) when administered in combination with anti-PD-1. Compound 19 also demonstrated adequate in vitro ADME and in vivo PK properties, displaying good oral bioavailability across multiple species (F % = 35–63). These findings summarize our compound’s favorable safety and efficacy profiles, justifying its testing in future translational studies. Check out the full publication here: https://lnkd.in/eZX_sZrV #MedicinalChemistry #Pharmacokinetic #efficacy #cancertreatment

Check out how antibody-drug conjugates (ADCs) are revolutionizing cancer treatment! 🚀 Unlike traditional therapies, ADCs act like "biological missiles," precisely targeting tumor cells with cytotoxic drugs while sparing healthy tissue. However, traditional ADCs, comprising full-length IgG antibodies linked to cytotoxic drugs, may face challenges in clinical efficacy, due to: ➡️Low tissue permeability and poor drug accumulation in tumours ➡️Slow pharmacokinetics and poor homogeneity Considering these issues, antibody fragments and protein scaffolds have been used for ADC development, such as single-chain variable fragments (scFvs) and single-domain antibodies (sdAbs). Check out this review article, published in Antibody Therapeutics that discusses ADCs engineered from small antibody fragments: https://hubs.li/Q02t85tS0 #AntibodyDrugConjugates #ADCs #AntibodyTherapeutics #AntibodyEngineering

Mutant KRAS proteins drive several different types of cancer and have historically been viewed as “undruggable.” This week at #ESMO24, Dr. Wungki Park of Memorial Sloan Kettering Cancer Center presented new Phase 1 data from ASP3082, our potential first-in-class targeted protein degrader in development for the treatment of solid tumors harboring KRAS G12D mutations. We were excited to share these results with the scientific community, and I am proud to be part of Astellas' efforts to develop treatments that could deliver meaningful outcomes to patients. Learn more about our Primary Focus #TargetedProteinDegradation and pipeline here: https://lnkd.in/gh-FvNGD

ADC OVERVIEW ADCs (antibody-drug conjugates) combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapeutic drugs, offering a targeted approach to eliminating tumor cells while sparing healthy tissue. After a period of fine-tuning, it was understood how to prepare these conjugates and then, in recent years, an increasing number of ADCs have been approved by regulatory agencies. The new generation of ADCs has a targeted, selective action, with demonstrated impressive clinical efficacy in various malignancies. Fabiano Visentin, Thomas Scattolin, et al. here publish a comprehensive and updated review of ADCs. In addition to traditional methods, based on the conjugation of maleimide and succinimide, new, unconventional strategies are emerging, such as photoconjugation, with advantages both in the synthesis process and in the quality of the synthesized ADCs. In the review, examples of ADCs containing metal-based and nature-inspired payloads are described. Special emphasis is placed on the different synthetic strategies that can be employed to conjugate the antibody with the selected payload, highlighting the advantages and disadvantages of each method. Further progress is expected, both technologically and in therapeutic applications such as, e.g., use in combination therapies with immune checkpoint inhibitors, CAR-T cells and small molecule inhibitors. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safe and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients. #ADC #Metallodrugs #CancerTherapy Giovanni Tonon, et al. Int. J. Mol. Sci. 2024, 25, 8651. https://lnkd.in/df5jip9v