Marc Tjwa’s Post

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

A groundbreaking study published in Cell Reports Medicine highlights a new hope for EGFR-mutant NSCLC patients. The study provides supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC. Notably, ctDNA was used as a biomarker to dynamically monitor minimal residual disease, aiding in the identification of patients responding to the treatment. This study, supported by Burning Rock's personalized MRD product, brPROPHET, underscores the importance of preoperative MRD testing in guiding dynamic monitoring and study design for patients with tumor gene mutations. 🔗 Read more: https://lnkd.in/gUDxmraw #LungCancer #CellReportsMedicine #BurningRock

Triple-negative breast cancer represents 15–20% of breast cancer cases and lacks targeted treatments. It is a biologically aggressive tumor characterized by moderate/high grade and highly proliferative cancer cells, which, together with limited treatment options, leads to the poorest prognosis among breast cancer subtypes. BRCA mutations, especially BRCA1, are strongly associated with TNBC risk. As per DelveInsight Business Research LLP’s estimates, out of all gene mutation specific TNBC cases in the United States in 2023, approximately 5,000 cases were BRAC gene mutation cases. Latest results from the PARTNER Trial (NCT03150576) at AACR 2024 assessed LYNPARZA (olaparib) with carboplatin and paclitaxel in neoadjuvant therapy for BRCA Wild-Type TNBC but didn't show improved outcomes compared to chemotherapy alone. For detailed findings, visit: https://lnkd.in/gYtNd8ku #breastcancer #triplenegativebreastcancer #AACR2024 #cancertreatment #neoadjuvant #BRAC #BRACgenemutations #genemutations #Olaparib

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

Boundless Bio Announces First Patient Dosed in First-in-Human Phase 1/2 Clinical Trial of BBI-825 in Cancer Patients with Resistance Gene Amplifications. We are excited to announce dosing of the first patient in our first-in-human study of BBI-825, our second program to enter the clinic, said Klaus Wagner M.D., Ph.D., Chief Medical Officer at Boundless Bio. BBI-825 represents a new approach in the potential treatment of oncogene amplifications, particularly in resistance associated with targeted therapy treatment of MAPK pathway-activated cancers. STARMAP (Study Treating Acquired Resistance: MAPK Amplifications) is an open-label, non-randomized, three-part Phase 1/2 clinical trial to evaluate the safety, pharmacokinetics, pharmacodynamic biomarkers, preliminary antitumor activity, and identify the maximum tolerated dose and recommended Phase 2 dose (RP2D) of BBI 825 administered as a single agent or in combination with select targeted therapies (NCT06299761). Part 1 is a dose escalation of BBI-825 as a monotherapy in patients with solid tumors. Part 2 is a combination dose escalation of BBI-825 and targeted therapies, encorafenib and cetuximab, or adagrasib and cetuximab, in patients with advanced or metastatic colorectal cancer with BRAFV600E or KRASG12C mutations, respectively, and co-occurring resistance gene amplifications. Part 3 is a combination dose expansion to evaluate preliminary anti-tumor activity at the RP2D of BBI-825 and each targeted therapy combination from Part 2. #oncology #oncologyresearch #clinicalresearch #clinicaltrials

Antibody-drug conjugates (ADCs) made several headlines at ESMO, here's a timely case that considers their use in an unusual case of HER2-mutated breast cancer. Be sure to follow CGC Genomics Consults AG to get the latest cases! #precisiononcology #cancergenomics #decisionsupport #patientadvocacy #CGP

This week we feature an unusual case of HER2-mutated breast cancer. Be sure to follow CGC Genomics Consults AG to get the latest cases, to share your comments on the case and to see our interpretation of the case in due course! #precisiononcology #cancergenomics #decisionsupport #patientadvocacy #CGP

𝐂𝐚𝐧𝐜𝐞𝐫 𝐆𝐞𝐧𝐨𝐦𝐢𝐜𝐬 𝐂𝐨𝐧𝐬𝐮𝐥𝐭 𝐨𝐟 𝐭𝐡𝐞 𝐖𝐞𝐞𝐤: 𝑻𝒂𝒓𝒈𝒆𝒕𝒊𝒏𝒈 𝑬𝑹𝑩𝑩2-𝑴𝒖𝒕𝒂𝒏𝒕 𝑯𝑬𝑹2+ 𝑴𝒆𝒕𝒂𝒔𝒕𝒂𝒕𝒊𝒄 𝑩𝒓𝒆𝒂𝒔𝒕 𝑪𝒂𝒏𝒄𝒆𝒓 𝒘𝒊𝒕𝒉 𝑨𝒏𝒕𝒊𝒃𝒐𝒅𝒚-𝑫𝒓𝒖𝒈-𝑪𝒐𝒏𝒋𝒖𝒈𝒂𝒕𝒆𝒔 (𝑨𝑫𝑪) 𝐂𝐚𝐬𝐞 𝐡𝐢𝐬𝐭𝐨𝐫𝐲: A 72-year-old female previously diagnosed with breast cancer was presented with lung and extensive bone metastases Histopathology confirmed invasive ductal carcinoma; ER negative, PR negative, Her2neu-2+ staining (ER-/PR-/HER2 equivocal) She was started on palliative chemotherapy with trastuzumab + pertuzumab + docetaxel and completed 12 cycles PET CT showed a good response, and continued on maintenance dual antibody therapy until disease progressed with new bone lesions, when treatment was changed to trastuzumab emtansine therapy with partial response to date. Genomic profiling was performed on a biopsy from the primary tumor site to aid clinical decision making. A highly-validated test was used, with sufficient tumor cellularity, so sensitivity for pertinent negatives was high: 𝐆𝐞𝐧𝐨𝐦𝐢𝐜 𝐏𝐫𝐨𝐟𝐢𝐥𝐢𝐧𝐠 𝐑𝐞𝐬𝐮𝐥𝐭𝐬: ·     ERBB2 S310F (no amplification detected) ·     PIK3CA H1047R ·     LYN amplification ·     CCND3 amplification ·     TP53 R248Q 𝐐𝐮𝐞𝐬𝐭𝐢𝐨𝐧𝐬 𝐟𝐫𝐨𝐦 𝐭𝐡𝐞 𝐨𝐧𝐜𝐨𝐥𝐨𝐠𝐢𝐬𝐭: 1) Compared to ERBB2 gene amplification, little is known about the efficacy of HER2-targeted therapy in patients with HER2-mutated metastatic breast cancer. Given that HER2 protein expression is equivocal and we are confident there is no gene amplification, would the patient benefit from HER2-targeted therapies? 2) Might a PIK3CA inhibitor be an option in this patient? 3) Are there any novel therapeutic combinations we should be aware of?   #precisiononcology #cancergenomics #decisionsupport #patientadvocacy #CGP Be sure to follow our page to receive the latest cases and interpretations!

#cancerresearch #metabolism #acidity #oncology https://lnkd.in/dnzFpUR7 Abstract Cancers undergo sequential changes to #proton (H+) #concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on #protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mutations influence pH balance, regulation or sensing in a manner that enables growth and invasion outside normal constraints as part of oncogenic transformation. These cancer-supporting effects become more prominent when #tumours develop an #acidic #microenvironment owing to metabolic reprogramming and disordered perfusion. The ensuing intracellular and extracellular pH disturbances affect multiple aspects of tumour biology, ranging from proliferation to immune surveillance, and can even facilitate further mutagenesis. As a selection pressure, extracellular acidosis accelerates disease progression by favouring acid-resistant cancer cells, which are typically associated with aggressive phenotypes. Although acid–base disturbances in tumours often occur alongside hypoxia and lactate accumulation, there is now ample evidence for a distinct role of H+-operated responses in key events underpinning cancer. The breadth of these actions presents therapeutic opportunities to change the trajectory of disease.

Veracyte, Inc. #Prostate #Decipher Prostate Genomic Classifier #NCCN Guidelines --Veracyte’s Decipher Prostate Test Receives Highest Evidence-Level Rating Among Molecular Tests in Updated Prostate Cancer NCCN Guidelines --The new NCCN Guidelines classify the Decipher Prostate test as Level 1B according to the “Simon Criteria,” which are published criteria for assigning a level of evidence for clinical biomarkers based on the quality and quantity of evidence available. NCCN summarizes the treatment implications for patients based on their Decipher score and the published evidence from analyses of multiple randomized, phase 3 clinical trials. https://lnkd.in/gV-BvR4P