About

Paul Fanta is a Clinical Professor of Medicine at UC San Diego, with a focus on the diagnosis and management of gastrointestinal cancers. His research incorporates biotechnology, bioinformatics, molecular biomarker analyses, and pharmacogenomic data within prospective clinical trials to better identify patients who will benefit from chemotherapy, avoid toxicities, and develop personalized therapeutic strategies. He prioritizes enrolling patients with cancers of the colon, rectum, anus, stomach, esophagus, GI stromal tumors, hepatocellular carcinoma, pancreas, gall-bladder, and cholangiocarcinoma into clinical trials. His educational background includes a BS in Biology/Chemistry/Math, an MS in Microbiology/Immunology, and an MD from the University of Arizona. He completed residency at Scripps-Green Hospital and a fellowship in Hematology-Oncology at Scripps Clinic. His work has contributed to advancing precision oncology, including molecular profiling of advanced malignancies, development of patient-derived tumor models, and exploring biomarkers for immunotherapy efficacy in gastrointestinal cancers.

Research topics

• Internal medicine
• Medicine
• Oncology
• Pathology
• Family medicine
• Intensive care medicine
• Surgery
• Cancer research
• Bioinformatics
• Gastroenterology
• Biology

Selected publications

• Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) N-of-1 Precision Oncology Study: Molecular Profiling to Match Individually Dosed, Personalized Drug Combinations

  Journal of Clinical Oncology · 2026-01-08 · 4 citations

  articleOpen access

  PURPOSE Malignancies have complex and distinct molecular profiles that may not segregate by tumor type. However, most precision oncology treatments are matched to a single biomarker. We aimed to optimize therapy for advanced cancers using individually dosed drug regimens customized to cotarget multiple molecular alterations. METHODS Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT; NCT02534675 ) is a prospective, investigator-initiated, multidepartment/pan-cancer trial for aggressive advanced/metastatic malignancies. Patients had tissue and/or blood next-generation sequencing (NGS; Foundation Medicine). A molecular tumor board made suggestions. Degree of biomarker matching to drugs given was calculated by a matching score (MS; broadly, number of pathogenic alterations targeted divided by total pathogenic alterations). RESULTS Overall, 210 evaluable patients (n = 456 consented) received ≥1 US Food and Drug Administration–approved drug (mostly off label) after NGS. Median number of pathogenic alterations/tumor was five (range, 0-20); approximately 95% of patients had unique molecular landscapes. Consistent with I-PREDICT's objective to optimize/tailor treatment for each patient, we administered 157 different regimens (including 103 personalized combinations without established safety/dosing data). For previously unstudied combinations, starting doses were reduced and titrated to tolerance (intrapatient dose-finding); only 6.5% experienced Grade 3/4 drug-related toxicities ( v 15.5% of those receiving established regimens). Higher disease control rate (stable disease ≥6 months/objective response), and longer progression-free survival and overall survival correlated significantly/independently/linearly with greater degrees of drug matching to alterations (higher MS), but did not vary by drug number or dosages. CONCLUSION The I-PREDICT strategy of maximizing personalized biomarker matching with individually dosed customized drug combinations enabled safe and active N-of-1 matched treatment, including regimens previously unstudied in Phase I trials. I-PREDICT represents a blueprint for a new personalized precision oncology paradigm, which merits validation via additional prospective trials.

  PublisherOA PDFDOI

• Cytoreductive Surgery in Patients With Metastatic Succinate Dehydrogenase‐Deficient Gastrointestinal Stromal Tumors

  Journal of Surgical Oncology · 2026-04-20

  articleOpen access

  BACKGROUND AND OBJECTIVES: Succinate dehydrogenase-deficient (SDH-deficient) gastrointestinal stromal tumors (GIST) are characterized by variable disease biology with poor responses to traditional tyrosine kinase inhibitors. The role of surgical intervention has been highly debated. METHODS: We performed a single-institution retrospective analysis of metastatic SDH-deficient GIST patients who underwent complete (CC-0) cytoreductive surgery (CRS) from 2017 to 2023. Pathologic-Peritoneal Cancer Index (P-PCI) and GIST Metastatectomy-Surgical Complexity Score (GM-SCS) were used to quantify complexity. Kaplan-Meier survival analysis compared time to progression on systemic therapy immediately before CRS (TTP-1L) and second to last line of systemic therapy before CRS (TTP-2L) versus time to recurrence (TTR) after CRS. RESULTS: Nine patients met inclusion criteria. The median age at CRS was 29 years (range: 17-43). Median P-PCI was 13 (IQR: 10-15) and median GM-SCS was 19 (IQR: 16-28). Clavien-Dindo grade ≥ 3 complication rate was 33.3% (3/9) within 90-days postoperatively. Median TTP-1L was unreached and median TTP-2L was 3.4 months (95% CI: 2.5-unreached), as compared to TTR at 26.1 months (95% CI: 15.2-unreached) post CRS (p ≤ 0.0001). CONCLUSIONS: Patients who underwent CC-0 CRS achieved prolonged disease control versus prior systemic therapies, suggesting that CRS may be a management option for highly selected SDH-deficient GIST patients.

  PublisherDOI

• Single Nuclei-Derived Molecular Subtypes of Gastrointestinal Stromal Tumors Correlate with Clinicopathologic Features and Predict Clinical Outcomes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-22

  preprintOpen access

  ABSTRACT Historically, gastrointestinal stromal tumor (GIST) has been subtyped by oncogenic driver mutations. However, tumors with the same mutational profile can have variable biology. To further explore the impact of molecular diversity on GIST biology, we performed single nucleus RNA sequencing on 16 primary GIST and utilized an integrated single cell atlas of the normal GI tract composed from multiple publicly available datasets to identify six distinct GIST cell states . We then statistically estimated the relative abundances of these profiles in bulk transcriptomic data. These were used to define six common GIST molecular subtypes based upon one or two predominant tumor cell states . We found that these molecular subtypes correlate with tumor locations, mutational profiles, and patient outcomes, and validated these subtypes in an independent international cohort. These molecular subtypes have the potential to be used for clinical prognostication for patients with GIST, identifying new therapeutic targets, and studying the cell of transformation of GIST.

  PublisherOA PDFDOI

• A Systematic Review with a Demonstrative Case of KIT and DOG-1 Expressing Gastrointestinal Stromal Tumors Harboring ETV6–NTRK3 Fusions

  Clinical Cancer Research · 2025-02-24 · 4 citations

  reviewOpen access

  PURPOSE: Previous reports have described ETV6-NTRK3 fusion-positive gastrointestinal stromal tumors (GIST) in cases lacking KIT, PDGFRA, RAS pathway, or SDHx alterations. However, some investigators have questioned the rigor of these reports and the true existence of NTRK rearrangements in GIST. This study aims to (i) resolve whether NTRK gene rearrangements exist in GIST; (ii) review the relevant literature; and (iii) demonstrate a case of GIST with NTRK fusion. EXPERIMENTAL DESIGN: A comprehensive literature review using PubMed identified additional NTRK fusion-reported cases. Under an institutional review board-approved protocol, we describe a patient with biopsy-proven GIST who underwent genomic and transcriptomic Clinical Laboratory Improvement Amendments-certified testing, precision-matched therapy, surgical resection, and pathologic analysis. RESULTS: We identified 17 reported cases of GIST with NTRK fusions. Five studies reported GIST with KIT/DOG-1 expression by IHC, wild-type KIT/PDGFRA, and an ETV6-NTRK3 fusion, consistent with GIST. We demonstrate a case of a 72-year-old female after resection of a high-risk gastric GIST followed by 45 months of adjuvant imatinib. She developed recurrent disease, and biopsy revealed mixed epithelioid and spindleoid GIST with IHC expression of KIT (CD117) and DOG-1. Imatinib was reinitiated, but her disease progressed, prompting molecular testing for the first time. RNA sequencing identified an in-frame fusion of ETV6 with NTRK3. Larotrectinib, a pan-NTRK inhibitor, was initiated at a dose of 100 mg twice daily for 7 months, resulting in shrinkage in five tumors (range, 4.2%-77%). Surgical cytoreduction demonstrated a pathologic near-complete response (1% viable tumor cells). CONCLUSIONS: Our findings confirm the existence of GIST with ETV6-NTRK3 fusion and demonstrate that these imatinib-resistant GIST may be exquisitely sensitive to tropomyosin receptor kinase inhibitors, although radiologic partial response may not be commensurate with pathologic responses.

  PublisherOA PDFDOI

• Gene- and immune-targeted therapy combinations using dual-matched biomarkers for patient selection

  npj Precision Oncology · 2025-07-24 · 2 citations

  articleOpen access

  Combinations of gene-targeted therapy and immune checkpoint inhibitors (ICIs) have been conducted, though generally without biomarker-based patient selection for both therapy types. We evaluated outcomes of 17 patients with advanced cancers treated with both targeted agents and ICIs, matched to distinct genomic and immune biomarkers, from a cohort of 715 cases discussed at our Molecular Tumor Board. Despite 29% of patients having undergone ≥3 prior therapies, the disease control rate (includes SD ≥ 6 months or objective response) was 53%, with a median progression-free survival (PFS) of 6.1 months (95% CI, 2.9-not estimable) and median overall survival (OS) of 9.7 months (95% CI, 6.7-not estimable). Three patients (~18%) achieved prolonged PFS and OS (PFS: 23.4+, 33.0, 59.7 months; OS: 23.4+, 43.6, 62.1+ months) in B-cell lymphoma unclassifiable, ovarian, and gastroesophageal cancers. Median dosages were 100% for ICIs and 50% for gene-targeted agents, with Grade 3-4 serious adverse events occurring in 24%. We additionally conducted a database search to evaluate the prevalence of biomarker-based dual therapy trials, which revealed only 1.3% (4/314) of such clinical trials included biomarkers for both targeted therapies and ICIs. These findings highlight the potential of dual biomarker-matched combination therapy even after multiple therapy lines and support further investigation of dual-matched therapy.

  PublisherOA PDFDOI

• Personalized <i>N</i> -of-1 Combination Therapies for Advanced Gastrointestinal Stromal Tumors

  JCO Precision Oncology · 2025-07-01 · 1 citations

  article

  PURPOSE Gastrointestinal stromal tumor (GIST) resistance to imatinib and other tyrosine kinase inhibitors poses an ongoing clinical challenge. We investigated molecularly matched combination therapies for treatment-refractory GIST, including drugs not previously combined in human studies. METHODS Patients of all ages with unresectable and/or metastatic GIST treated with combination therapies were included (February 13, 2015-December 31, 2022). These patients were discussed at molecular tumor board and enrolled in the prospective Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) study (ClinicalTrials.gov identifier: NCT02534675 ). Patient demographics, tumor next-generation sequencing (NGS), treatment responses, and survival outcomes were retrospectively analyzed. RESULTS Six (1.6%) patients met the inclusion criteria. The median age at diagnosis was 59.5 years with the majority (4/6) of patients being male. NGS revealed median of six deleterious genomic alterations per patient excluding variants of unknown significance. Five (5/6) patients had KIT -mutant GIST, and one patient had BRAF V600E -mutant GIST. Two thirds of tumors had CDKN2A/B loss. Patients received median of 1 (range, 1-3) customized combination therapy consisting of median of 2 (range, 2-3) drugs targeting median of 2 (range, 2-4) genomic alterations. One patient experienced a treatment-related grade ≥3 adverse event (hypertension). For all patients, the best response by RECIST v1.1 was stable disease (SD). Combination therapies led to SD ≥6 months (range, 6.2-11.3 months) in four (4/6) patients compared with none in the immediate previous single-agent targeted therapies (SD range, 1.5-5.4 months). Most (5/6) patients had at least 60% prolongation of their progression-free survival compared with their immediate previous single-agent targeted therapy. CONCLUSION Our results demonstrate that a multitargeted, biomarker-matched combination approach can be safely administered to obtain disease control. Tailored combination therapies for advanced GIST with multiple genomic alterations warrant further investigation.

  PublisherDOI

• Quantification of PD-L1 expression and tumor mutational burden in biologically distinct advanced pancreatic cancers responding to pembrolizumab: case reports

  Frontiers in Immunology · 2024-12-02 · 1 citations

  articleOpen accessSenior authorCorresponding

  Background: The advent of checkpoint therapy is one of the most important recent advancements in cancer therapy. Though checkpoint therapy is a mainstay in some cancers, it has been largely ineffective in treating cancers of the pancreas. Pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors are seldom responsive to checkpoint inhibition. Case presentations: Here we present two cases of advanced pancreatic cancers that either failed to respond or recurred following conventional treatments. Tissue from each tumor was sequenced and analyzed for PD-L1 expression. Each patient was started on checkpoint blockade after assessing for a predictive biomarker, either the combined positive score or the tumor mutational burden. In each case, checkpoint blockade led to durable radiographic responses. Conclusions: We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

  PublisherOA PDFDOI

• Supplementary Tables 1-3, Supplementary Figure 1, and supplementary references from The Mutational Landscape of Gastrointestinal Malignancies as Reflected by Circulating Tumor DNA

  2023-04-03

  supplementary-materialsOpen access

  &lt;p&gt;Supplemental Table 1: Genes comprising liquid DNA sequencing panel; Supplemental Table 2: Examples of gene alterations and potential targeted therapies; Supplemental Table 3: Correlation between alterations as detected by tissue or liquid biopsy; Figure S1: Bar plot of less-commonly altered genes&lt;/p&gt;

  PublisherDOI

• Data from Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience

  2023-04-03

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next-generation sequencing (NGS) results were evaluated. Outcomes for patients who received a “matched” versus “unmatched” therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a “matched” therapy, 93 (26.8%) with an “unmatched” therapy. More patients in the matched group achieved stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR), 34.5% vs. 16.1%, (&lt;i&gt;P&lt;/i&gt; ≤ 0.020 multivariable or propensity score methods). Matched patients had a longer median progression-free survival (PFS; 4.0 vs. 3.0 months, &lt;i&gt;P&lt;/i&gt; = 0.039 in the Cox regression model). In analysis using PFS1 (PFS on the prior line of therapy) as a comparator to PFS after NGS, as expected, the unmatched group demonstrated a PFS2 significantly shorter than PFS1 (&lt;i&gt;P&lt;/i&gt; = 0.009); however, this shortening was not observed in the matched patients (&lt;i&gt;P&lt;/i&gt; = 0.595). Furthermore, 45.3% of the matched patients (24/53) had a PFS2/PFS1 ratio ≥1.3 compared with 19.3% of patients (11/57) in the unmatched group (&lt;i&gt;P&lt;/i&gt; = 0.004 univariable and &lt;i&gt;P&lt;/i&gt; ≥ 0.057 in multivariable/propensity score analysis). Patients with a “matching-score” (the number of matched drugs divided by the number of aberrations; unmatched patients had a score of zero) &gt; 0.2 had a median overall survival (OS) of 15.7 months compared with 10.6 months when their matching-score was ≤ 0.2, (&lt;i&gt;P&lt;/i&gt; = 0.040 in the Cox regression model). Matched versus unmatched patients had higher rates of SD ≥ 6 months/PR/CR and longer PFS, and improvement in OS correlated with a higher matching score in multivariable analysis. &lt;i&gt;Mol Cancer Ther; 15(4); 743–52. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Data from On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker Actionability in 439 Patients

  2023-04-03

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;Despite the increased use of molecular diagnostics, the extent to which patients who have these tests harbor potentially actionable aberrations is unclear. We retrospectively reviewed 439 patients with diverse cancers, for whom next-generation sequencing (mostly 236-gene panel) had been performed. Data pertaining to the molecular alterations identified, as well as associated treatment suggestions (on- or off-label, or experimental), were extracted from molecular diagnostic reports. Most patients (420/439; 96%) had at least one molecular alteration: 1,813 alterations (in 207 distinct genes) were identified [the majority being mutations (62%) or amplifications (29%)]. The three most common gene abnormalities were &lt;i&gt;TP53&lt;/i&gt; (44%), &lt;i&gt;KRAS&lt;/i&gt; (16%), and &lt;i&gt;PIK3CA&lt;/i&gt; (12%). The median number of alterations per patient was 3 (range, 0–16). Nineteen patients (4%) had no alterations; 48 patients (11%) had only one alteration; and 372 patients had two or more abnormalities (85%). The median number of potentially actionable anomalies per patient was 2 (range, 0–8). Most patients (393/439; 90%) had at least one potentially actionable alteration, and in all these cases the aberration could at least be targeted by an experimental drug in a clinical trial. A total of 307 patients (70%) had an alteration that was actionable with an approved drug, but in only 89 patients (20%) was the drug approved for their disease (on-label). Next-generation sequencing identified theoretically actionable aberrations in 90% of our patients. Many of the drugs are, however, experimental or would require off-label use. Strategies to address drug access for patients harboring potentially actionable mutations are needed. &lt;i&gt;Mol Cancer Ther; 14(6); 1488–94. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

Frequent coauthors

• Razelle Kurzrock

  Medical College of Wisconsin Cancer Center

  148 shared

• Shumei Kato

  89 shared

• Jason K. Sicklick

  University of California, San Diego

  81 shared

• David Piccioni

  UC San Diego Health System

  73 shared

• Maria Schwaederlé

  58 shared

• Scott M. Lippman

  56 shared

• Gregory A. Daniels

  University of California, San Diego

  51 shared

• Adam M. Burgoyne

  Moores Cancer Center

  50 shared