KRAS mutated colorectal cancers with or without PIK3CA mutations: Clinical and molecular profiles inform current and future therapeutics

Voutsadakis, Ioannis A.

doi:10.1016/j.critrevonc.2023.103987

Cited by 10 publications

(3 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations in the most frequently mutated genes in colon cancer, such as KRAS, APC, TP53, SMAD4, PIK3CA, and BRAF, are known to be oncogenic in almost all the cases. Mutations in other genes, such as ATM and epigenetic regulators, are of unknown significance in some cases [35,36]. These observations highlight the complexity of transcriptional regulation of tight junction proteins.…”

Section: Discussionmentioning

confidence: 99%

Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer

Voutsadakis

2023

CIMB

Self Cite

View full text Add to dashboard Cite

Metastatic colon cancer remains incurable despite improvements in survival outcomes. New therapies based on the discovery of colon cancer genomic subsets could improve outcomes. Colon cancers from genomic studies with publicly available data were examined to define the expression and regulation of the major tight junction proteins claudins and occludin in genomic groups. Putative regulations of the promoters of tight junction genes by colon-cancer-deregulated pathways were evaluated in silico. The effect of claudin mRNA expression levels on survival of colon cancer patients was examined. Common mutations in colon-cancer-related genes showed variable prevalence in genomically identified groups. Claudin genes were rarely mutated in colon cancer patients. Genomically identified groups of colon cancer displayed distinct regulation of claudins and occludin at the mRNA level. Claudin gene promoters possessed clustered sites of binding sequences for transcription factors TCF4 and SMADs, consistent with a key regulatory role of the WNT and TGFβ pathways in their expression. Although an effect of claudin mRNA expression on survival of colon cancer patients as a whole was not prominent, survival of genomic subsets was significantly influenced by claudin mRNA expression. mRNA expression of the main tight junction genes showed differential regulation in various genomically defined subgroups of colon cancer. These data pinpoint a distinct role of claudins and pathways that regulate them in these subgroups and suggest that subgroups of colon cancer should be considered in future efforts to therapeutically target claudins.

show abstract

Section: Discussionmentioning

confidence: 99%

Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer

Voutsadakis

2023

CIMB

Self Cite

View full text Add to dashboard Cite

show abstract

“…PIK3CA activating mutation, encoding the p110α catalytic subunit of PI3K, is the most commonly mutated oncogene detected across tumor lineages [15,54]. Indeed, PIK3CA is usually either mutated or amplified in several human cancers [55], including colorectal cancer (CRC) [56], breast [57], lung [58], gastric [59], prostate [60], and cervical cancer [61,62]. Most mutations are found close to spots E545K (exon 9) and H1047 (exon 20).…”

Section: Pi3k Mutation and Amplification In Cancermentioning

confidence: 99%

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Glaviano,

Foo,

Lam

et al. 2023

Mol Cancer

422

View full text Add to dashboard Cite

The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

show abstract

“…The hyperactivation of the PI3K/AKT/mTOR pathway is closely linked to the development of resistance to various forms of treatment, such as chemotherapy and targeted therapy, as well as the progression of cancer [ 5 ]. In a variety of cancer types, including breast cancer [ 6 ], colorectal cancer [ 7 ], lung cancer [ 8 ], gastric cancer [ 9 ] and esophageal cancer [ 10 ], the PIK3CA gene is frequently mutated or amplified. Which leads to PI3K activation and serves as a key determinant of standard anticancer therapy [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Capivasertib reverses chemotherapy-induced esophageal cancer resistance via inhibiting Akt-associated Mcl-1 upregulation

Kai,

Kang,

Jiang

et al. 2024

Heliyon

View full text Add to dashboard Cite

KRAS mutated colorectal cancers with or without PIK3CA mutations: Clinical and molecular profiles inform current and future therapeutics

Cited by 10 publications

References 101 publications

Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer

Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Capivasertib reverses chemotherapy-induced esophageal cancer resistance via inhibiting Akt-associated Mcl-1 upregulation

Contact Info

Product

Resources

About