Publications by authors named "Bristi Basu"

Purpose: BT5528 is a Bicycle Toxin Conjugate, a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting EphA2 tumor antigen, linked to a cytotoxin (monomethyl auristatin E [MMAE]). EphA2 is overexpressed in many solid tumors and contributes to oncogenesis, tumor-associated angiogenesis, and metastasis.

Materials And Methods: The primary objectives were to investigate the safety and tolerability of BT5528 and to define the maximum-tolerated dose, if observed, and recommended phase II dose (RP2D)/expansion dose.

View Article and Find Full Text PDF

Objectives: The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort.

Methods: Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy.

View Article and Find Full Text PDF
Article Synopsis
  • - A Phase I trial tested the safety and tolerability of MOv18 IgE, a new type of chimeric IgE antibody, in cancer patients whose tumors express folate receptor-alpha, with a focus on minimizing allergic reactions.
  • - The study involved dose escalation from 70 μg to 12 mg, using skin prick and basophil activation tests to identify low-risk patients; the main side effect noted was temporary hives, with one case of anaphylaxis linked to pre-existing reactive basophils.
  • - Results indicate that MOv18 IgE therapy is tolerable and shows potential anti-tumor activity, evidenced by a positive response in a patient with ovarian cancer, suggesting that IgE-based
View Article and Find Full Text PDF

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined.

View Article and Find Full Text PDF

Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites.

View Article and Find Full Text PDF
Article Synopsis
  • Chemotherapy for metastatic pancreatic adenocarcinoma has limited effectiveness, and there's a need for reliable biomarkers to predict patient outcomes.
  • In a study of 146 patients, factors like poor performance status, liver metastases, and detectable KRAS ctDNA were linked to worse overall survival, while a drop in albumin levels at 4 weeks was particularly indicative of poorer outcomes.
  • The findings suggest that easily measurable patient factors can help predict chemotherapy success, but the utility of KRAS ctDNA requires more research.
View Article and Find Full Text PDF

Clinical trials for oncology drug development have long relied on surrogate outcome biomarkers that assess changes in tumor burden to accelerate drug registration (i.e., Response Evaluation Criteria in Solid Tumors version 1.

View Article and Find Full Text PDF

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies.

View Article and Find Full Text PDF
Article Synopsis
  • CT900 is a new small molecule drug that inhibits thymidylate synthase and targets tumors overexpressing the α-folate receptor (α-FR).
  • In a clinical trial, doses between 1-12 mg/m2 were tested on patients with high-grade serous ovarian cancer, focusing on a dose of 12 mg/m2 given every two weeks.
  • The trial showed manageable side effects and a 21.9% overall response rate, with better outcomes in patients who had higher α-FR expression, indicating that CT900 has potential for further study.
View Article and Find Full Text PDF
Article Synopsis
  • This study aimed to assess glioblastoma metabolism using hyperpolarized carbon-13 MRI by tracking the exchange of hyperpolarized carbon from injected [1-C]pyruvate to tumor lactate and bicarbonate.
  • Seven treatment-naive GBM patients underwent imaging, revealing that the bicarbonate-to-pyruvate ratio was significantly lower in tumors compared to normal brain areas, while lactate levels were similar.
  • The research indicated strong correlations between the intensities of lactate and bicarbonate signals and pyruvate, suggesting variations in tumor metabolism that could have implications for understanding glioblastoma.
View Article and Find Full Text PDF

Purpose: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models.

Experimental Design: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38).

View Article and Find Full Text PDF

Purpose: To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib.

Methods: A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation.

View Article and Find Full Text PDF

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic.

Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project.

View Article and Find Full Text PDF
Article Synopsis
  • CH5126766 (VS-6766) is a new drug that inhibits MEK and RAF pathways, showing potential anti-tumor effects against various solid tumors, but initial development faced challenges due to toxicity.
  • A study was conducted at the Royal Marsden NHS Foundation Trust to evaluate the safety and dosing of CH5126766 through different intermittent schedules in patients with advanced tumors or multiple myeloma with specific genetic mutations.
  • The study included a dose-escalation phase to identify tolerable dosing and a dose-expansion phase to assess the drug’s effectiveness in patients selected based on biomarkers, focusing on safety and anti-tumor activity.
View Article and Find Full Text PDF

Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response.

View Article and Find Full Text PDF

Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected.

View Article and Find Full Text PDF

Pre-clinical models have shown that targeting pancreatic stellate cells with all-trans-retinoic-acid (ATRA) reprograms pancreatic stroma to suppress pancreatic ductal adenocarcinoma (PDAC) growth. Here, in a phase Ib, dose escalation and expansion, trial for patients with advanced, unresectable PDAC (n = 27), ATRA is re-purposed as a stromal-targeting agent in combination with gemcitabine-nab-paclitaxel chemotherapy using a two-step adaptive continual re-assessment method trial design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D, primary outcome) is the FDA/EMEA approved dose of gemcitabine-nab-paclitaxel along-with ATRA (45 mg/m orally, days 1-15/cycle).

View Article and Find Full Text PDF

Purpose: To compare hyperpolarized carbon 13 (C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer.

Materials And Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent C MRI after injection of hyperpolarized [1-carbon 13 {C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The C-labeled lactate-to-pyruvate ratio derived from hyperpolarized C MRI and the pharmacokinetic parameters transfer constant ( ) and washout parameter ( ) derived from DCE MRI were compared before and after treatment.

View Article and Find Full Text PDF
Article Synopsis
  • Preclinical studies suggest that combining PARP inhibitors (like olaparib) with PI3K/AKT pathway inhibitors (like capivasertib) is effective for treating certain tumors.
  • An investigator-led phase I trial tested this combination on 64 patients with advanced solid tumors, using an intrapatient dose-escalation approach to determine safety and efficacy.
  • Results showed that 44.6% of patients experienced clinical benefits, and the combination was well tolerated, indicating potential for further development in future clinical trials.
View Article and Find Full Text PDF

: Sorafenib for advanced hepatocellular carcinoma (HCC) is dose adjusted by toxicity. Preliminary studies have suggested an association between plasma concentrations of sorafenib and its main metabolite (M2) and clinical outcomes. This study aimed to validate these findings and establish target values for sorafenib trough concentrations.

View Article and Find Full Text PDF

Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α.

Patients And Methods: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases.

View Article and Find Full Text PDF

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized C label exchange between injected [1-C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic C MRSI was performed following injection of hyperpolarized [1-C]pyruvate.

View Article and Find Full Text PDF

Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.

View Article and Find Full Text PDF