Management Of Colorectal Cancer Research Articles

Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value.

Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.

New advances in artificial intelligence for the diagnosis and treatment of colorectal cancer: a literature review

Introduction: With 1.93 million new instances of colorectal cancer (CRC) reported in 2020, the disease presents a danger to world health. With its potential to improve CRC management, artificial intelligence (AI) has become increasingly prominent in the medical field. This research attempts to evaluate the current status of AI applications in CRC diagnosis and treatment, considering regional differences in healthcare systems and populations. Methodology: On databases like ScienceDirect, Google Scholar, and PubMed, a systematic literature evaluation was carried out using search phrases including "artificial intelligence," "colorectal cancer," "diagnosis," and "treatment." English-language research on AI applications in CRC diagnosis and treatment that were published during the previous five years met the inclusion criteria. Results: Endoscopic, non-invasive, histological, and radiographic techniques are among the AI applications used in CRC diagnosis. Prognostic forecasts, diagnostic accuracy, and tumor segmentation are all significantly enhanced by AI. AI helps with targeted therapy and chemoradiotherapy decision-making, improves surgical accuracy, and helps with personalized regimens. Conclusion: The use of AI in colorectal cancer management has the potential for timely identification, precise diagnosis, and customized care. Continuous developments in AI algorithms and clinical data support the development of precision medicine, which offers significant gains in CRC treatment and detection.

Enhancing Oral Delivery and Anticancer Efficacy of 7-Ethyl-10-Hydroxycamptothecin through Self-assembled Micelles of Deoxycholic Acid Grafted N'-nonyl-trimethyl Chitosan

Irinotecan (CPT-11) is used as a first or second-line chemotherapy drug for the treatment and management of colorectal cancers. In vitro studies have shown that 7-ethyl-10-hydroxycamptothecin (SN38), the active metabolite of CPT-11, displays promising anticancer efficacy. However, its poor aqueous solubility and hydrolytic degradation result in its lower oral bioavailability and impracticable clinical application. To overcome these limitations, a novel amphiphilic chitosan derivative, deoxycholic acid decorated N’-nonyl-trimethyl chitosan, was synthesized. Nano-micelles loaded with SN38 were subsequently prepared to enhance the bioavailability and anti-tumor efficacy of the drug through oral administration. The nano-micelles demonstrated improved dilution stability, enhanced greater mucosal adherence, significant P-gp efflux inhibition, and increased drug transport in the intestine by paracellular and transcellular pathways. Consequently, both the in vivo pharmacokinetic profile and therapeutic efficacy of SN38 against cancer were substantially improved via the micellar system. Thus, the developed polymeric micelles can potentially enhance the SN38 oral absorption for cancer therapy, offering prospective avenues for further exploration.

Causes of death in patients operated for colorectal cancer

BackgroundColorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. MethodsAn Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. ResultsA total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65–0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42–0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59–5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64–28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36–3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68–0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. ConclusionThere is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.

Role of the artificial intelligence in the management of T1 colorectal cancer

Approximately 10% of submucosal invasive (T1) colorectal cancers demonstrate extraintestinal lymph node metastasis, necessitating surgical intervention with lymph node dissection. The ability to identify T1b (submucosal invasion depth ≥ 1000 µm) as a risk factor for lymph node metastasis via pre-treatment endoscopy is crucial in guiding treatment strategies. Accurately distinguishing T1b from T1a (submucosal invasion depth < 1000 µm) or dysplasia remains a significant challenge for artificial intelligence (AI) systems, which require high and consistent diagnostic capabilities. Moreover, as endoscopic therapies like endoscopic full-thickness resection and endoscopic intermuscular dissection evolve, and the focus on reducing unnecessary surgeries intensifies, the initial management of T1 colorectal cancers via endoscopic treatment is anticipated to increase. Consequently, the development of highly accurate and reliable AI systems is essential, not only for pre-treatment depth assessment but also for post-treatment risk stratification of lymph node metastasis. While such AI diagnostic systems are still under development, significant advancements are expected in the near future to improve decision-making in T1 colorectal cancer management.

Abstract A025: Adaptive therapy: Leveraging evolutionary dynamics for colorectal cancer management in vivo

Abstract Therapeutic resistance to chemotherapy is frequently the proximate cause of cancer treatment failure and, ultimately, patient mortality. Evolutionary therapies have been developed to address this problem and potentially reduce toxicities. The most successful strategy to date, adaptive therapy (AT), is designed to use chemosensitive cells to out-compete and suppress the chemoresistant cells. However, detailed observations to elucidate the mechanisms of AT's success are lacking. Typically, AT involves lowering the dose of the chemotherapy, thereby reducing toxicity and preserving the immune system. We are evaluating AT for the first time in colorectal cancer, using syngeneic orthotopic xenograft models. This project marks several firsts: 1) sensitive and resistant clones will be tracked longitudinally, 2) AT will be tested with a targeted therapy (MRTX1133), 3) AT will be tested in an immune competent model, 4) multiple drugs will be used for AT, and 5) extinction therapy will be tested in mice. We will employ genetic barcodes and differential luciferase tagging to track the tumor cell subpopulations longitudinally. Currently, we are conducting an in-vivo pilot experiment to validate our protocol, emphasizing tumor engraftment efficacy and tracking cell subpopulations. Additionally, we are investigating the potential of Lactobacillus acidophilus to inhibit tumor growth, augment chemotherapy, and bolster immune response in colorectal cancer. Citation Format: Harley I. Richker, Gissel Marquez-Alcaraz, Carlo Maley. Adaptive therapy: Leveraging evolutionary dynamics for colorectal cancer management in vivo [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A025.

Current Trends in the Biomarker'sDiscovery for the Treatment and Management of Colorectal Cancer: A ComprehensiveReview.

Colorectal cancer (CRC) is a significant health issue, with countless individuals suffering. With its bleak outlook, the number of deaths caused by CRC can only be reduced if new diagnostic and prognostic biomarkers are identified and developed quickly. Recent developments in screening programme development and patient management have been encouraging, but many unanswered questions still need to be addressed before a customized colorectal cancer approach can be implemented. Prevention of diseases, the detection of them in their early stages, the analysis of the severity, and the treatment of any metastasized diseases are all paramount. Despite the increased utilization of genetic profiles in decision-making processes, such as the selection of therapy and predicting drug response, there are only a limited number of validated biomarkers for colorectal cancer that are suitable for clinical practice. To further research into colorectal carcinogenesis, pinpoint prospective indicators, and validate these indicators, creating non-intrusive, sensitive, and exact biomarkers is an urgent requirement. This procedure is reliant on translational proteomics. This investigation serves as a comprehensive resource on the current state of genetic and epigenetic biomarkers in diagnosing, predicting, and evaluating colorectal cancer. It underscores the transformative potential of these biomarkers in advancing CRC patient care, from early detection to personalized treatment strategies. However, it also underscores the need for ongoing research and validation to realize their clinical utility fully.

In vitro and in vivo antineoplastic activities of solamargine in colorectal cancer through the suppression of PI3K/AKT pathway.

Previous research has demonstrated the efficacy of SM in inhibiting tumor growth in various cancer types. The objective of this study was to examine the antineoplastic effects and molecular mechanisms of Solamargine (SM) in colorectal cancer. Colorectal cancer (CRC) cells were treated with different concentrations of SM to evaluate the anticancer concentration for further experimental measurements. Additionally, the antitumor efficacy of SM was assessed in a subcutaneously implanted tumor model of colorectal cancer. RNA-seq and bioinformatics analyses were employed to identify differentially expressed genes (DEGs) and elucidate the underlying molecular mechanisms in LoVo3 cells. Subsequently, the specific mechanism of SM-mediated anti-tumor activities was analyzed by protein expression methods. The results of in vitro assays demonstrated that SM exhibits significant inhibitory effects on cell proliferation, clone formation, and invasion, while also promoting apoptosis in SW48 and LOVO3 cells. In a mouse xenograft tumor model, intragastric administration of SM at doses of 5 or 10 mg/kg effectively suppressed tumor volume and weight, and induced cell apoptosis in vivo. SM treatment also down-regulated PCNA and Cyclin E protein expression, contributing to the regulation of apoptosis. Further analysis using RNA-seq, bioinformatics, and experimental measurements revealed that SM treatment upregulates PTEN expression, while significantly reducing the phosphorylation levels of Akt and mTOR in LOVO3 cells. Our study provides further evidence to support the notion that SM primarily induces apoptosis in colorectal cancer cells through the inhibition of the PI3K/Akt signaling pathway. Additionally, our investigation demonstrated the favorable safety profile of SM in a mouse model of colorectal cancer, thereby suggesting its potential as a promising therapeutic approach for the management of CRC.

Integrated blood and organ profile analysis to evaluate ameliorative effects of kaempferol on 5-fluorouracil-induced toxicity

Colorectal cancer (CRC) treatment strategies encompass a triad of medical interventions: surgery, radiotherapy, and chemotherapy. Among these, the use of chemotherapy, specifically 5-fluorouracil (5-FU), has become a cornerstone in CRC management. However, it is imperative to explore novel approaches that harness the synergistic potential of chemotherapy agents alongside adjunctive compounds to mitigate the severe adverse effects that often accompany treatment. In light of this pressing need, this study focuses on evaluating Kaempferol (KMP) in combination with 5-FU in a DMH-induced CRC animal model, scrutinizing its impact on haematological indices, organ health, and gastrointestinal, hepatotoxic, and nephrotoxic effects. Remarkably, KMP demonstrated haemato-protective attributes and exerted an immunomodulatory influence, effectively counteracting 5-FU-induced damage. Furthermore, organ assessments affirm the safety profile of the combined treatments while suggesting KMP's potential role in preserving the structural integrity of the intestine, and spleen. Histopathological assessments unveiled KMP's capacity to ameliorate liver injury and mitigate CRC-induced renal impairment. These multifaceted findings underscore KMP's candidacy as a promising adjunctive therapeutic option for CRC, underlining the pivotal need for personalized therapeutic strategies that concurrently optimize treatment efficacy and safeguard organ health. KMP holds tremendous promise in elevating the paradigm of CRC management.

DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.

Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC.

Contemporary management of advanced colorectal cancer: the Australian experience.

Contemporary management of advanced colorectal cancer: the Australian experience.

Photodynamic Therapy as a Desirable Approach in the Treatment of Colorectal Cancer, with Special Focus on Photodynamic Nanotherapeutics in Immunotherapy.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide; however, there is not a convincing treatment for this disease. Limitations of conventional CRC therapies force scientists to develop novel treatment concepts for both primary care alongside adjuvant therapy. Photodynamic therapy (PDT) has been introduced as a promising therapeutic procedure for CRC mediated through theranostic principle in which special dyes, photosensitizers (PSs), are excited by near-infrared (NIR) and visible light. Recent studies showed that PDT has synergistic effects in combination with chemotherapy or immunotherapy in the treatment of CRC patients. Of note, nanoformulation of PS or immunotherapeutic agents could augment the PDT effectiveness. In this review, we summarize PDT application in CRC management with a special focus on the nanoparticles-based delivery system from the perspective of targeting deeper CRC and increased PDT efficiency, which could provide a desirable approach for clinical translation.

Recent Approaches on Molecular Markers, Treatment and Novel Drug Delivery System Used for the Management of Colorectal Cancer: A Comprehensive Review.

Colorectal cancer affects 1 in 25 females and 1 in 24 males, making it the third most frequent cancer with over 6,08,030 deaths worldwide, despite advancements in detection and treatments, including surgery, chemotherapeutics, radiotherapy, and immune therapeutics. Novel potential agents have increased survival in acute and chronic disease conditions, with a higher risk of side effects and cost. However, metastatic disease has an insignificant long-term diagnosis, and significant challenges remain due to last-stage diagnosis and treatment failure. Early detection, survival, and treatment efficacy are all improved by biomarkers. The advancement of cancer biomarkers' molecular pathology and genomics during the last three decades has improved therapy. Clinically useful prognostic biomarkers assist clinical judgment, for example, by predicting the success of EGFR-inhibiting antibodies in the presence of KRAS gene mutations. Few biomarkers are currently used in clinical settings, so further research is still needed. Nanocarriers, with materials like Carbon nanotubes and gold nanoparticles, provide targeted CRC drug delivery and diagnostics. Light-responsive drugs with gold and silica nanoparticles effectively target and destroy CRC cells. We evaluate the potential use of the long non-coding RNA (non-coding RNA) oncogene plasmacytoma variant translocation 1 (PVT1) as a diagnostic, prognostic, and therapeutic biomarker, along with the latest nanotech breakthroughs in CRC diagnosis and treatment.

Incorporating Novel Technologies in Precision Oncology for Colorectal Cancer: Advancing Personalized Medicine

Colorectal cancer (CRC) is one of the most heterogeneous and deadly diseases, with a global incidence of 1.5 million cases per year. Genomics has revolutionized the clinical management of CRC by enabling comprehensive molecular profiling of cancer. However, a deeper understanding of the molecular factors is needed to identify new prognostic and predictive markers that can assist in designing more effective therapeutic regimens for the improved management of CRC. Recent breakthroughs in single-cell analysis have identified new cell subtypes that play a critical role in tumor progression and could serve as potential therapeutic targets. Spatial analysis of the transcriptome and proteome holds the key to unlocking pathogenic cellular interactions, while liquid biopsy profiling of molecular variables from serum holds great potential for monitoring therapy resistance. Furthermore, gene expression signatures from various pathways have emerged as promising prognostic indicators in colorectal cancer and have the potential to enhance the development of equitable medicine. The advancement of these technologies for identifying new markers, particularly in the domain of predictive and personalized medicine, has the potential to improve the management of patients with CRC. Further investigations utilizing similar methods could uncover molecular subtypes specific to emerging therapies, potentially strengthening the development of personalized medicine for CRC patients.

Precision endoscopy in colorectal polyps' characterization and planning of endoscopic therapy.

Precision endoscopy in the management of colorectal polyps and early colorectal cancer has emerged as the standard of care. It includes optical characterization of polyps and estimation of submucosal invasion depth of large nonpedunculated colorectal polyps to select the appropriate endoscopic resection modality. Over time, several imaging modalities have been implemented in endoscopic practice to improve optical performance. Among these, image-enhanced endoscopy systems and magnification endoscopy represent now well-established tools. New advanced technologies, such as endocytoscopy and confocal laser endomicroscopy, have recently shown promising results in predicting the histology of colorectal polyps. In recent years, artificial intelligence has continued to enhance endoscopic performance in the characterization of colorectal polyps, overcoming the limitations of other imaging modes. In this review we retrace the path of precision endoscopy, analyzing the yield of various endoscopic imaging techniques in personalizing management of colorectal polyps and early colorectal cancer.

Impact of revising colorectal cancer screening guidelines on health care resources in Canada.

78 Background: The rising incidence of early-onset colorectal cancer (CRC) has prompted U.S. organizations to lower the recommended CRC screening age for average risk adults from 50 to 45 years old, while Canadian programs remain unchanged. Canadian guidelines also differ from the U.S. in preferentially screening with a fecal immunochemical test (FIT) and recommending against colonoscopies as a screening test. Differences in national healthcare administration warrants investigation into the resource impact of updating screening guidance in Canada. Methods: Microsimulation modeling was performed using OncoSim (version 3.6) to project health and economic outcomes of different CRC screening strategies based on Canadian population data. Four simulated birth cohorts of the Canadian population born between 1973–1992 were tracked for a 40-year span from the year the oldest in each cohort turned 40 until the youngest in the same cohort turned 75. Colorectal adenoma rates were adjusted according to cohort risk ratios estimated from historical incidence data to reflect real-world CRC rates. Outcomes were reported for the cumulative cohort. Results: Compared to FIT screening at age 50, FIT screening at 45 reduced deaths by 5,220, incidence by 11,980, and added 96,100 health-adjusted life years (HALY). Colonoscopy screening at age 45 led to 17,870 fewer deaths, 74,250 fewer cases and added 314,960 HALYs. FIT and colonoscopy screening at age 45 had incremental costs of CAD$3,259 and $7,881 per HALY gained vs. a FIT at age 50, respectively. Across screening strategies, the greatest benefits were observed in the youngest cohort. Colonoscopy screening at age 45 resulted in 10,679,540 more total colonoscopies than the current capacity of 8,966,979 with FIT screening at age 50. Lowering the screening age to 45 with a FIT increased colonoscopy demand by 329,555. The total cost of CRC care (screening, diagnosis and treatment) increased with lower screening ages and colonoscopy first modalities, while the cost of CRC management (diagnosis and treatment) decreased with lower screening ages and colonoscopy first approaches. Conclusions: Adjusting current CRC screening guidelines demonstrates significant resource implications with proportional health benefits. Lower screening ages and colonoscopy first approaches have the largest resource demand and greatest health outcomes, while the incremental cost per HALY gained for all screening strategies is modest compared to standard benchmarks. [Table: see text]

Cyclophilin A: An Independent Prognostic Factor for Survival in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab and Chemotherapy.

Colorectal cancer (CRC) ranks as second most common cause of cancer-related deaths. The CRC management considerably improved in recent years, especially due to biological therapies such as bevacizumab. The lack of predictive or prognostic biomarkers remains one of the major disadvantages of using bevacizumab in the CRC management. We performed a prospective study to analyze the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) investigated by ELISA in 56 patients with metastatic CRC undergoing bevacizumab and chemotherapy between May 2019 and September 2021 at baseline and after one and six months of therapy. We showed that low levels of CypA at baseline and after one month of treatment were associated with better overall survival (OS) (42 versus 24 months, p = 0.029 at baseline; 42 versus 25 months, p = 0.039 after one month). For copeptin and Tie2, Kaplan-Meier curves showed no correlation between these biomarkers and OS or progression-free survival. When adjusting for baseline and post-treatment factors, a multivariate Cox analysis showed that low values of CypA at baseline and after one month of treatment were independent prognostic factors for OS and correlated with a better prognosis in metastatic CRC patients.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1β, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Evaluation of mismatch-repair and microsatellite-instability status in a Chinese colorectal cancer Cohort

BackgroundImmunohistochemistry (IHC) and traditional polymerase chain reaction (PCR) are the methods of choice in clinical practice to identify the mismatch repair (MMR) and microsatellite instability (MSI) status in colorectal cancer (CRC). In some previous researches, the concordance rate between two methods was different and discordance existed in about 1 %–9.7 %. MethodsWe retrospectively reviewed 406 patients received surgical CRC resections and tests of both MMR IHC and MSI PCR from January 2019 to April 2022 in Shanghai Changzheng Hospital. The incidence of deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) CRCs, the concordance rate between two methods, and the reasons for discordant results were evaluated with clinicopathological data, immunochemical staining, whole-exome sequencing, and MLH1 methylation analysis. ResultsAmong 406 patients, the incidence of MSI-H CRCs was 7.88 %. Nearly a quarter of the cases under reexamination of IHC was initial misinterpreted. Besides, the concordance rate between MMR IHC and MSI PCR was 99.26 % (401 of 404) and the Kappa value was 0.945 (p < 0.001). Finally, some somatic variants of MMR and POLE genes which may explain the discordance were identified. ConclusionThe incidence rate of MSI-H in Chinese patients with CRC might be relatively low owing to tumor location. Although MSI and IHC analyses are highly concordant, both MMR IHC and MSI PCR tests should be simultaneously performed and MMR IHC should be interpreted by experienced pathologists. In the future, further studies on discordant results should be carried out to improve the personalized management of CRC.

68Ga-FAPI PET imaging monitors response to combined TGF-βR inhibition and immunotherapy in metastatic colorectal cancer.

BACKGROUNDImproving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor-β receptor (TGF-βR) inhibitor that targets cancer-associated fibroblasts (CAFs) is promising for the enhancement of efficacy of immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy.METHODSWe measured CAFs in vivo using the 68Ga-labeled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04) for PET/CT imaging to guide the combination of TGF-β inhibition and immunotherapy. One hundred thirty-one patients with metastatic colorectal cancer (CRC) underwent 68Ga-FAPI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging. The relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed in patients. Mouse cohorts of metastatic CRC were treated with the TGF-βR inhibitor combined with KN046, which blocks programmed death ligand 1 (PD-L1) and CTLA-4, followed by 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses.RESULTSPatients with metastatic CRC demonstrated high uptake rates of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. The TGF-βR inhibitor enhanced tumor-infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamic changes of CAFs and tumor response to combined the TGF-βR inhibitor with immunotherapy.CONCLUSION68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and the response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to guide precise TGF-β inhibition plus immunotherapy in CRC patients, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.TRIAL REGISTRATIONCFFSTS Trial, ChiCTR2100053984, Chinese Clinical Trial Registry.FUNDINGNational Natural Science Foundation of China (82072695, 32270767, 82272035, 81972260).