Alberto Bardelli
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View article: The molecular and functional landscape of resistance to FOLFIRI chemotherapy in metastatic colorectal cancer
The molecular and functional landscape of resistance to FOLFIRI chemotherapy in metastatic colorectal cancer Open
The combination of 5-fluorouracil and irinotecan (FOLFIRI) remains a standard-of-care treatment for metastatic colorectal cancer (mCRC), yet benefits only about half of patients. Using patient-derived xenografts (PDXs), we investigated the…
View article: KRAS G12C Inhibition in Solid Tumors: Biological Breakthroughs, Clinical Evidence, and Open Challenges
KRAS G12C Inhibition in Solid Tumors: Biological Breakthroughs, Clinical Evidence, and Open Challenges Open
KRAS is the most frequently mutated oncogene in cancer. Its activating mutations are associated with aggressive tumor behavior and resistance to certain therapies, including anti-EGFR treatments in colorectal cancer. In particular, the KRA…
View article: Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models
Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models Open
View article: Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells
Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells Open
View article: Early-Onset Colorectal Cancers Exhibit Distinctive Placental-Like Features
Early-Onset Colorectal Cancers Exhibit Distinctive Placental-Like Features Open
The incidence of early-onset colorectal cancer (EO-CRC, diagnosed earlier than age 50) is rising worldwide. Despite distinctive clinicopathological features, whether EO-CRC represents a biologically distinct entity from standard-onset CRC …
View article: Correction: Preoperative ctDNA retains prognostic relevance beyond postoperative assessment in stage II–III colon cancer
Correction: Preoperative ctDNA retains prognostic relevance beyond postoperative assessment in stage II–III colon cancer Open
View article: Figure S6 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S6 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S6 shows the basal levels of protein expression and phosphorylation in a set of PDAC cell lines, determined by Western blot, and the Western blot analysis of the signaling response to RMC-7977 in AsPC-1 and HS766.T, grown in regular…
View article: Figure S1 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S1 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S1 shows the dose-response curves of RMC-7977 in a panel of human cancer cell lines harboring mutations in RAS and belonging to three different lineages.
View article: Data from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Data from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
RAS genes are frequently mutated in cancer, often at codons 12 and 61. With the recent introduction of RAS inhibitors, we can now directly investigate the effects of specific RAS mutations in cancer cells. In this study, we demonstr…
View article: Figure S2 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S2 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S2 shows the dose-response Western blot analysis of MIA PaCa-2 treated with different concentrations of RMC-7977 for 1h and 24h, the Western blot analysis of early signaling dynamics following treatment with trametinib in six repres…
View article: Figure S10 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S10 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S10 shows the pulldown of GTP-bound RAS in PANC-1 and SW480 treated with DMSO, RMC-7977 (10nM), Cetuximab (25μg/mL), or their combination for 24 hours, and the dose-response pharmacology assay of AsPC-1 cells treated with different …
View article: Figure S4 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S4 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S4 shows the Western blot analysis of the MAPK and PI3K pathway responses to RMC-7977, trametinib, alpelisib 1μM / AZD-8186, and the respective combinations in COLO678 and Sk-Mel-176, and the drug combination validation experiments …
View article: Figure S3 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S3 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S3 shows the Western blot analysis of early signaling dynamics following treatment with trametinib in two HTVI-KRAS G12D and two HTVI-KRAS Q61R lines.
View article: Figure S5 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S5 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S5 shows the effect of EGF stimulation in a set of lines treated or not with RAS inhibitors.
View article: Figure S8 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S8 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S8 shows the viability of HPAF-II after exposure to RMC-7977 10nM (with or without Cetuximab 25μg/mL) or trametinib 10nM (with or without Cetuximab 25μg/mL) for 96h.
View article: Figure S7 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S7 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S7 shows the pulldown of GTP-bound RAS in AsPC-1 and HS766.T, serum-starved overnight, then pretreated with DMSO or RMC-7977, and finally stimulated with EGF.
View article: Figure S11 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S11 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S11 shows the efficacy of RMC-7977 alone and in combination with Cetuximab in a patient-derived xenografts of PDAC or Melanoma harboring a KRAS G12D or NRAS Q61K mutation, respectively, and the drug combination validation experiment…
View article: Figure S9 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S9 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S9 shows the dose-response curves of RMC-7977 alone or in combination with Cetuximab 25μg/mL in a panel of human cancer cell lines harboring RAS G12X or RAS Q61X mutations.
View article: Figure S12 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Figure S12 from Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
Figure S12 shows the bar plots showing the prevalence of each RAS mutation in patients not exposed to anti-EGFR treatment or after anti-EGFR therapy, and the RAS alterations when multiple codons were involved in the “acquired” subgroup.
View article: 44P Rechallenge with anti-HER2 regimens in metastatic colorectal cancer: The retrospective RHEA study
44P Rechallenge with anti-HER2 regimens in metastatic colorectal cancer: The retrospective RHEA study Open
View article: Preoperative ctDNA retains prognostic relevance beyond postoperative assessment in stage II–III colon cancer
Preoperative ctDNA retains prognostic relevance beyond postoperative assessment in stage II–III colon cancer Open
In cancer patients, only a small fraction of circulating cell-free DNA (cfDNA) consists of circulating tumor DNA (ctDNA), which contains tumor-specific features. Detecting ctDNA in peripheral blood through liquid biopsy offers a safe, noni…
View article: Cisplatin and temozolomide combinatorial treatment triggers hypermutability and immune surveillance in experimental cancer models
Cisplatin and temozolomide combinatorial treatment triggers hypermutability and immune surveillance in experimental cancer models Open
View article: <scp>TRPM8</scp> levels determine tumor vulnerability to channel agonists
<span>TRPM8</span> levels determine tumor vulnerability to channel agonists Open
Targeted therapies have pervasively enhanced clinical protocols and significantly improved survival and quality of life of cancer patients. Mostly grounded on small molecules and antibodies targeting deregulated mechanisms in cancer cells,…
View article: Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations Open
RAS genes are frequently mutated in cancer, often at codons 12 and 61. With the recent introduction of RAS inhibitors, we can now directly investigate the effects of specific RAS mutations in cancer cells. In this study, we demonstrate tha…
View article: Clinical utility and future perspectives of liquid biopsy in colorectal cancer
Clinical utility and future perspectives of liquid biopsy in colorectal cancer Open
Liquid biopsy analyses of circulating tumor DNA are emerging as transformative tools for colorectal cancer management, enabling disease detection, monitoring, and treatment. Here, we critically assess its evidence-based utility in current …
View article: A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC)
A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC) Open
View article: A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers
A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers Open
Background Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting in resistance. We previously found that dual c-MET/MEK1/2 inhibi…
View article: Acidosis overrides molecular heterogeneity to shape therapeutically targetable metabolic phenotypes in colon cancers
Acidosis overrides molecular heterogeneity to shape therapeutically targetable metabolic phenotypes in colon cancers Open
Colorectal cancer (CRC) represents a prototypical example of a cancer type for which inter- and intra-tumor heterogeneities remain major challenges for the clinical management of patients. Besides genotype-mediated phenotypic alterations, …
View article: When molecular biology transforms clinical oncology: the <scp>EGFR</scp> journey in colorectal cancer
When molecular biology transforms clinical oncology: the <span>EGFR</span> journey in colorectal cancer Open
The discovery of growth factors and their involvement in cancer represents the foundation of precision oncology. The preclinical and clinical development of agents targeting epidermal growth factor receptor (EGFR) in colorectal cancer (CRC…
View article: Assessing vaccine hesitancy and vaccine literacy in the European prison population: a multicenter repeated cross-sectional study
Assessing vaccine hesitancy and vaccine literacy in the European prison population: a multicenter repeated cross-sectional study Open
The study aimed to quantify vaccine hesitancy and vaccine literacy in prison populations and assess their correlation prior and after the implementation of training and information activities targeting PLP. A repeated cross-sectional obser…