FAP overexpression

We also detected increased secretion of CSF1, a cytokine involved in myeloid recruitment and differentiation. Our findings suggest that the mechanism of FAP-targeted therapies are through effects on the immune microenvironment and anti-tumor immune response.

The CUT&RUN results indicated that FAP expression was regulated by STAT3, which could bind to the FAP promoter region and regulate its transcription status. We concluded that IL-17a promoted HCC by increasing FAP expression in HSCs via activation of the STAT3 signaling pathway.

Moreover, a pilot translational investigation demonstrated that [68Ga]Ga-DOTA-FD1 had the capability to identify both primary and metastatic tumors with precision and distinction. In summary, we developed [68Ga]Ga-DOTA-FD1 for same-day PET imaging of FAP dynamics and [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 for effective radioligand therapy of FAP-overexpressing tumors.

This overview focuses on the various radiochemical strategies for obtaining [99mTc]Tc-FAPi tracers, highlighting the main challenges encountered and possible solutions when applying each distinct approach. Additionally, it covers the preclinical and initial clinical applications of [99mTc]Tc-FAPi in cancer and inflammation.

Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy...However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact. Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.

Radiolabeled FAPI can improve the detection, staging, and assessment of treatment response in breast and the most common gynecologic malignancies, but the problem with normal hormone-responsive organs remains insurmountable. Compared to the diagnostic applications of FAPI, further research is needed for future therapeutic applications.

The FAP overexpression promoted proliferation and migration while inhibiting the apoptosis of HCC cells. The FAP overexpression promoted the progression of HCC by regulating the immunity to affect the prognosis of HCC patients, thereby serving as a poor prognostic marker for HCC patients.

[177Lu]Lu-SB03178 exhibited a combination of high and sustained tumor uptake, with excellent tumor-to-critical organ uptake ratios resulting in a high radiation absorbed dose to the tumor and a low estimated whole-body dose to humans. Our preliminary findings are considerably encouraging to support clinical development of [68Ga]Ga-/[177Lu]Lu-SB03178 theranostic pair for use in a vast majority of FAP-overexpressing neoplasms, particularly carcinomas.

As we continue to deepen our understanding of this novel imaging technique, it is hoped that FAPI PET imaging will play an increasingly important role in the fight against cancer. However, as with any new technology, further research is needed to fully understand the potential and limitations of FAPI PET imaging in the clinical setting.

Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.

High intratumoral FAP expression was associated with worse survival, suggesting that intratumoral FAP expression represents malignant progression in patients with IHCC.

Postsurgical pathologic report verified the diagnosis of ectopic papillary thyroid carcinoma. High FAP expression in the tumor sample corresponded to its imaging manifestations.

Further molecular dynamics simulations showed the binding stability of the proposed natural products. This work recommends repurposing ginsenoside C and Rg1 as potential binders for the selected targets and endorses future experimental validation for the treatment of oral cancer.

Although FAP CAFs have attracted increasing attention for their role in cancer, the feasibility and efficacy of FAP-targeting therapies for HNSCC remain doubtful.

Further interrogation of this rich resource could provide insight into the function of CAFs and could reveal putative stromal targets. We describe for the first time that heat shock protein β-6 (HSPB6/HSP20) and cyclooxygenase 1 (PTGS1/COX1) are overexpressed in CAFs compared to cancer cells.

It is possible that FAP could be a reliable biomarker for the diagnosis and prognosis of ccRCC because of its role in the ccRCC progression via triggering the PI3K/AKT/mTOR signaling pathway.

In conclusion, DTPA-700DX-MB binds to FAP-expressing cells and targets PDAC299 tumours in mice with good signal-to-background ratios. Furthermore, the induced apoptosis indicates the feasibility of targeted depletion of FAP-expressing cells with photodynamic therapy.

In summary, we employed bioinformatic tools and experiments to perform a comprehensive analysis about FAP. Up-regulation of FAP in gastrointestinal cancers was primarily expressed in fibroblasts and contributes to tumor cells motility, macrophages infiltration and M2 polarization, revealing the multifactorial role of FAP in gastrointestinal cancers progression.

In many studies, FAP has been evaluated as a therapeutic target and diagnostic factor into which the current review tries to provide a comprehensive insight. Video Abstract.

The majority of the sarcoma samples showed FAP expression by both stromal and tumor/nonstromal cells. Further investigation of FAP as a potential diagnostic and therapeutic target in sarcomas is warranted.

Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.

Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.

Knockdown of FAP could reverse tumorigenicity and chemoresistance in CRC cells. Thus, FAP may serve as a marker for prognosis and therapeutic outcome, as well as a potential therapeutic target to overcome chemoresistance in MC patients.

Importantly, the meta-analysis showed that FAP had an overall positive rate of 68 % (63-73 %, 95 % CI; n = 382) and the patients with high expression of FAP showed a poor prognosis in terms of OS (HR=1.82, 1.33-2.48, 95 % CI) in gastric cancer. In short, FAP, ASPN and CTHRC1 were identified as potential prognostic and diagnostic biomarkers related with immunity and might be effective therapeutic targets of gastric cancer, and the significance of FAP for the prognosis was further assessed by meta-analysis.

Single doses of Lu-FAP6-IP-DOTA suppressed tumor growth by about 45% in all tested tumor models without causing reproducible toxicities. We conclude that Lu-FAP6-IP-DOTA constitutes a promising candidate for FAP-targeted RLT of solid tumors.

In recent years, several publications on FAP overexpression in gastrointestinal tumors have been published. The only published meta-analysis on this topic dates to 2015. It included 15 studies on various solid tumors and only 8 studies focusing exclusively on gastrointestinal tumors. The expected results of the present analysis will provide new evidence on the prognostic value of FAP in gastrointestinal tumors and thereby support health care professionals and patients in their decision-making.

In line with this result, immunohistochemistry demonstrated high FAP expression on tumor stroma. Accuracy is under investigation in an ongoing investigator-initiated trial.

We additionally determined the effects of FAP-α overexpression on the human fibrosarcoma HT1080 cell line that showed increased migration, accompanied by limited changes in metabolism that identified the dependency of the metabolic changes on cell type. These metabolic data identify a previously unknown role of FAP-α in modifying cancer cell metabolism in the TNBC cell line studied here that may provide new insights into its functional roles in cancer progression.

(4) CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.

[68Ga]Ga-FAPI-46 PET/CT seems useful to improve detection of nodal metastasis in patients with CCs. Future studies should aim to compare [68Ga]Ga-FAPI-46 PET/CT to surgical staging of pelvic and para-aortic LNs in patients with locally advanced CC.

FAP in the CT combined with TLSs was shown to have significant prognostic value in predicting CRC recurrence after curative resection.

A strong positive correlation was observed between TBR and V for [Ga]Ga-FAPI-04. TBR reflects FAP receptor density better than SUV and SUV, and would be the preferred measurement tool for semiquantitative assessment of [Ga]Ga-FAPI-04 tumor uptake and as a means for evaluating treatment response.

Furthermore, we discuss whether targeting FAP-overexpressing CAFs could represent a potential therapeutic strategy and describe the development of FAP-targeted probes for diagnostic imaging. Finally, we assess the emerging basic and clinical studies regarding the bench-to-bedside translation of FAP in pancreatic cancer.

GLUT4 and FAP expression was significantly associated with increased intratumor MVD and adverse clinicopathological factors.

A reduction of endogenous FAP-α+ murine CAFs was identified at 7 days after FAP-α-IR700-PIT. FAP-α-targeted NIR-PIT presents a promising strategy to eliminate FAP-α+ CAFs.

More importantly, this probe was successfully applied to the measurement of FAP activity levels in plasma from gastric cancer patients for the first time. A significant enhancement in FAP levels was observed in patients with gastric cancer, suggesting that the FAP level may be a potential diagnostic parameter for gastric cancer.

The study shows a specific FAP positive fibroblast-subset of cases with poor prognosis restricted to a CD8 high density group of HGSC. Therapy targeting the immunosuppressive action of fibroblasts may be a tool to enhance the known positive prognostic effect of CD8-cells in ovarian cancer and may be explored in T-cell depended immune therapy.

C-RJ1101 and C-RJ1102 are interesting candidates for translation to the clinic, taking advantage of the shorter half-life and physical imaging properties of C-11.

This study presents the spatiotemporal evolution of novel neoplastic associations in syndromic medulloblastoma, and discusses the post-radiotherapy risk for secondary malignancies in syndromic pediatric patients, with important implications for the biology, diagnosis, and therapy of these tumors. Video Abstract.