Research Strategies for Low-Survival Cancers

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Feb 12

PMID 33573275

Authors

Caroline Conway

Denis M Collins

Amanda McCann

Kellie Dean

Affiliations

Soon will be listed here.

Abstract

While substantial progress has been made to improve the diagnosis, prognosis, and survivorship of patients with cancer, certain cancer types, along with metastatic and refractory disease, remain clinical challenges. To improve patient outcomes, ultimately, the cancer research community must meet and overcome these challenges, leading to improved approaches to treat the most difficult cancers. Here, we discuss research progress aimed at gaining a better understanding of the molecular and cellular changes in tumor cells and the surrounding stroma, presented at the 56th Irish Association for Cancer Research (IACR) Annual Conference. With a focus on poor prognosis cancers, such as esophageal and chemo-resistant colorectal cancers, we highlight how detailed molecular knowledge of tumor and stromal biology can provide windows of opportunity for biomarker discovery and therapeutic targets. Even with previously characterized targets, such as phosphoinositide 3-kinase (PI3K), one of the most altered proteins in all human cancers, new insights into how this protein may be more effectively inhibited through novel combination therapies is presented.

References

Frohne C, Llano E, Perkovic A, Cohen R, Luke J . Complete response of metastatic melanoma in a patient with Crohn's disease simultaneously receiving anti-α4β7 and anti-PD1 antibodies. J Immunother Cancer. 2019; 7(1):1. PMC: 6322234. DOI: 10.1186/s40425-018-0484-x. View

Pages F, Mlecnik B, Marliot F, Bindea G, Ou F, Bifulco C . International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018; 391(10135):2128-2139. DOI: 10.1016/S0140-6736(18)30789-X. View

Ghiringhelli F, Fumet J . Is There a Place for Immunotherapy for Metastatic Microsatellite Stable Colorectal Cancer?. Front Immunol. 2019; 10:1816. PMC: 6691024. DOI: 10.3389/fimmu.2019.01816. View

Yuan T, Cantley L . PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008; 27(41):5497-510. PMC: 3398461. DOI: 10.1038/onc.2008.245. View

Nishana M, Ha C, Rodriguez-Hernaez J, Ranjbaran A, Chio E, Nora E . Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation. Genome Biol. 2020; 21(1):108. PMC: 7212617. DOI: 10.1186/s13059-020-02024-0. View

Gray R, Loughrey M, Bankhead P, Cardwell C, McQuaid S, ONeill R . Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study. Br J Cancer. 2017; 116(12):1652-1659. PMC: 5518863. DOI: 10.1038/bjc.2017.139. View

Gray R, Cantwell M, Coleman H, Loughrey M, Bankhead P, McQuaid S . Evaluation of PTGS2 Expression, PIK3CA Mutation, Aspirin Use and Colon Cancer Survival in a Population-Based Cohort Study. Clin Transl Gastroenterol. 2017; 8(4):e91. PMC: 5543466. DOI: 10.1038/ctg.2017.18. View

Voena C, Chiarle R . Advances in cancer immunology and cancer immunotherapy. Discov Med. 2016; 21(114):125-33. View

McCain R, McManus D, McQuaid S, James J, Salto-Tellez M, Reid N . Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study. Cancer Causes Control. 2019; 31(1):1-11. PMC: 6942597. DOI: 10.1007/s10552-019-01247-2. View

10.

Lee V, Le D . Efficacy of PD-1 blockade in tumors with MMR deficiency. Immunotherapy. 2015; 8(1):1-3. DOI: 10.2217/imt.15.97. View

11.

Weber D, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger R, Kofler B . Ketogenic diet in the treatment of cancer - Where do we stand?. Mol Metab. 2019; 33:102-121. PMC: 7056920. DOI: 10.1016/j.molmet.2019.06.026. View

12.

Diaz Jr L, Le D . PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015; 373(20):1979. DOI: 10.1056/NEJMc1510353. View

13.

Van Cutsem E, Cervantes A, Adam R, Sobrero A, van Krieken J, Aderka D . ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016; 27(8):1386-422. DOI: 10.1093/annonc/mdw235. View

14.

Engelman J, Luo J, Cantley L . The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006; 7(8):606-19. DOI: 10.1038/nrg1879. View

15.

Moskwa P, Buffa F, Pan Y, Panchakshari R, Gottipati P, Muschel R . miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell. 2011; 41(2):210-20. PMC: 3249932. DOI: 10.1016/j.molcel.2010.12.005. View

16.

Wheless J . History of the ketogenic diet. Epilepsia. 2008; 49 Suppl 8:3-5. DOI: 10.1111/j.1528-1167.2008.01821.x. View

17.

Hopkins B, Pauli C, Du X, Wang D, Li X, Wu D . Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018; 560(7719):499-503. PMC: 6197057. DOI: 10.1038/s41586-018-0343-4. View

18.

Donnelly C, Cairnduff V, Chen J, Kearney T, Fitzpatrick D, Fox C . The completeness and timeliness of cancer registration and the implications for measuring cancer burden. Cancer Epidemiol. 2017; 49:101-107. DOI: 10.1016/j.canep.2017.05.007. View

19.

OMalley G, Treacy O, Lynch K, Naicker S, Leonard N, Lohan P . Stromal Cell PD-L1 Inhibits CD8 T-cell Antitumor Immune Responses and Promotes Colon Cancer. Cancer Immunol Res. 2018; 6(11):1426-1441. DOI: 10.1158/2326-6066.CIR-17-0443. View

20.

Loughrey M, Bankhead P, Coleman H, Hagan R, Craig S, McCorry A . Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis. Histopathology. 2018; 73(2):327-338. DOI: 10.1111/his.13516. View