Precision Oncology: 2023 in Review

Murciano-Goroff, Yonina R.; Suehnholz, Sarah P.; Drilon, Alexander; Chakravarty, Debyani

doi:10.1158/2159-8290.cd-23-1194

Cited by 11 publications

(5 citation statements)

References 31 publications

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“…Crizotinib is a Tyrosine Kinase Inhibitor (TKI) targeted ALK which not only has high anti-tumor activity against ALK-positive IMT, but also can reduce the tumor volume of ALK-negative patients ( 19 ), indicating that ALK-targeted drugs may be a treatment option for such kind of bladder IMT. Alectinib, originally designed for ALK fusion-positive non-small cell lung cancer (NSCLC), has been recently incorporated into the NCCN guidelines (version 2023) for ALK-positive inflammatory myofibroblastic tumors ( 20 ). It is worth noting that absent ALK expression of IMT has a relatively higher risk of distant metastasis ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

A rare huge bladder inflammatory myofibroblastic tumor treated by en bloc resection with diode laser: a case report and literature review

Yuan,

Wang,

Sun

et al. 2024

Front. Oncol.

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BackgroundInflammatory myofibroblastic tumor (IMT) is a rare neoplasm with malignant potential. Bladder IMT is even rarer and mainly treated by surgical resection However, partial or radical cystectomy would affect the quality of life of patients due to major surgical trauma, and classical TURBT is hard to avoid intraoperative complications including obturator nerve reflex and bleeding etc. Therefore, the safe and effective better choice of surgical approaches become critical to bladder IMT.Case presentationA 42-year-old male patient was admitted to the department of urology with persistent painless gross hematuria for more than 10 days without the presentation of hypertension. Preoperative routine urine examination of red blood cells was 7738.9/HPF (normal range ≤ 3/HPF). CTU indicated a space occupying lesion (6.0 cm×5.0 cm) in the left posterior wall of the bladder with heterogeneous enhancement in the excretory phase. MRI also indicated bladder tumor with slightly equal SI on T1WI and mixed high SI on T2WI (6.0 cm×5.1cm×3.5cm) in the left posterior wall of the bladder. En bloc resection of bladder IMT with 1470 nm diode laser in combination of removing the enucleated tumor by the morcellator system was performed. Postoperative pathological examination revealed bladder IMT, with IHC positive for Ki-67 (15-20%), CK AE1/AE3, SMA, and Desmin of bladder IMT and negative for ALK of bladder IMT as well as FISH negative for ALK gene rearrangement. Second TUR with 1470 nm diode laser was performed within 6 weeks to reduce postoperative risk of recurrence due to highly malignant potential for the high expression of Ki-67 (15-20%) and negative ALK in IHC staining. The second postoperative pathology report showed chronic inflammation concomitant with edema of the bladder mucosa without bladder IMT, furthermore no tumor was observed in muscularis propria layer of bladder. No recurrence occurred during the period of 24-month follow-up.ConclusionEn bloc resection of bladder IMT in combination of the following second transurethral resection with 1470 nm diode laser is a safe and effective surgical approach for the huge bladder IMT with highly malignant potential.

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Section: Discussionmentioning

confidence: 99%

A rare huge bladder inflammatory myofibroblastic tumor treated by en bloc resection with diode laser: a case report and literature review

Yuan,

Wang,

Sun

et al. 2024

Front. Oncol.

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“…Adagrasib, another KRASG12C inhibitor, has shown clinical activity in KRASG12C-mutated tumors, including PDAC [65]. Both inhibitors, FDA-approved for KRASG12C-mutant non-small cell lung cancer (NSCLC), trap KRASG12C in its inactive GDP-bound state and are now listed in the national comprehensive cancer network (NCCN) clinical practice guidelines as for additional KRASG12Cmutant histologies, including pancreatic and colorectal cancers [66]. Another more potent GDP-bound KRASG12C inhibitor, divarasib, in combination with various anti-cancer therapies (Table 1), has shown promising clinical benefit in a small cohort of patients with pancreatic adenocarcinoma harboring the KRASG12C mutation [67].…”

Section: Kras Inhibitionmentioning

confidence: 99%

“…The first in class of these inhibitors, RMC-6232, forms a tricomplex with RAS(ON) and an abundant intracellular chaperon protein cyclophilin A, sterically inhibiting RAS binding to its effectors [72,73]. RMC-6232 is being assessed in a phase I clinical trial for KRASG12-mutant tumors (Table 1) and appears effective against KRAS position 12 (G12X) mutants, including G12D, G12V and G12R, inducing durable suppression of the RAS pathway activation in preclinical cellular in vitro and in vivo xenograft PDAC models [66,73].…”

Section: Kras Inhibitionmentioning

confidence: 99%

Inhibition of the RAF/MEK/ERK Signaling Cascade in Pancreatic Cancer: Recent Advances and Future Perspectives

Adamopoulos,

Cave,

Papavassiliou

2024

IJMS

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Pancreatic cancer represents a formidable challenge in oncology, primarily due to its aggressive nature and limited therapeutic options. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC), the main form of pancreatic cancer, remains disappointingly poor with a 5-year overall survival of only 5%. Almost 95% of PDAC patients harbor Kirsten rat sarcoma virus (KRAS) oncogenic mutations. KRAS activates downstream intracellular pathways, most notably the rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling axis. Dysregulation of the RAF/MEK/ERK pathway is a crucial feature of pancreatic cancer and therefore its main components, RAF, MEK and ERK kinases, have been targeted pharmacologically, largely by small-molecule inhibitors. The recent advances in the development of inhibitors not only directly targeting the RAF/MEK/ERK pathway but also indirectly through inhibition of its regulators, such as Src homology-containing protein tyrosine phosphatase 2 (SHP2) and Son of sevenless homolog 1 (SOS1), provide new therapeutic opportunities. Moreover, the discovery of allele-specific small-molecule inhibitors against mutant KRAS variants has brought excitement for successful innovations in the battle against pancreatic cancer. Herein, we review the recent advances in targeted therapy and combinatorial strategies with focus on the current preclinical and clinical approaches, providing critical insight, underscoring the potential of these efforts and supporting their promise to improve the lives of patients with PDAC.

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“…For instance, we may now target KRAS mutations due to the advent of selective KRASG12C inhibitors [13]. Additionally, there are multiple ongoing studies examining how to combine these selective inhibitors with other forms of therapy in addition to looking at non-G12C KRAS alleles [15]. Still, druggable driver mutations currently appear in low frequency amongst the cancer population, limiting the effectiveness of targeted treatment [16].…”

Section: Introductionmentioning

confidence: 99%

Precision Immuno-Oncology in NSCLC through Gender Equity Lenses

Marks,

Sridhar,

et al. 2024

Cancers

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Precision immuno-oncology involves the development of personalized cancer treatments that are influenced by the unique nature of an individual’s DNA, immune cells, and their tumor’s molecular characterization. Biological sex influences immunity; females typically mount stronger innate and adaptive immune responses than males. Though more research is warranted, we continue to observe an enhanced benefit for females with lung cancer when treated with combination chemoimmunotherapy in contrast to the preferred approach of utilizing immunotherapy alone in men. Despite the observed sex differences in response to treatments, women remain underrepresented in oncology clinical trials, largely as a result of gender-biased misconceptions. Such exclusion has resulted in the development of less efficacious treatment guidelines and clinical recommendations and has created a knowledge gap in regard to immunotherapy-related survivorship issues such as fertility. To develop a more precise approach to care and overcome the exclusion of women from clinical trials, flexible trial schedules, multilingual communication strategies, financial, and transportation assistance for participants should be adopted. The impact of intersectionality and other determinants of health that affect the diagnosis, treatment, and outcomes in women must also be considered in order to develop a comprehensive understanding of the unique impact of immunotherapy in all women with lung cancer.

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Precision Oncology: 2023 in Review

Cited by 11 publications

References 31 publications

A rare huge bladder inflammatory myofibroblastic tumor treated by en bloc resection with diode laser: a case report and literature review

A rare huge bladder inflammatory myofibroblastic tumor treated by en bloc resection with diode laser: a case report and literature review

Inhibition of the RAF/MEK/ERK Signaling Cascade in Pancreatic Cancer: Recent Advances and Future Perspectives

Precision Immuno-Oncology in NSCLC through Gender Equity Lenses

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