Research

Major cancer signaling pathways

Mohammed Y Refai 1*

1 Department of Biochemistry, College of Science, University of Jeddah, Jeddah-21589 Saudi Arabia.

* Correspondence: hmbaeissa@uj.edu.sa (H.M.B.)

Citation: Refai, M.Y. Major cancer signalling pathways. Glob. Jour. Bas. Sci. 2025, 1(8). 1-6.

Received: April 27, 2025

Revised: June 10, 2025

Accepted: June 26, 2025

Published: June 29, 2025

doi: 10.63454/jbs20000040

ISSN: 3049-3315

Volume 1; Issue 8

Download PDF file

Abstract: Cancer development and progression are driven by dysregulated cellular signaling pathways that control proliferation, survival, metabolism, and immune evasion. Aberrant activation of oncogenic pathways and inactivation of tumor suppressor signaling result in uncontrolled cell growth and therapy resistance. This short review summarizes the major cancer-associated signaling pathways, including PI3K/AKT/mTOR, MAPK, Wnt/β-catenin, JAK/STAT, NF-κB, TGF-β, Notch, Hedgehog, p53, and Hippo pathways. We highlight their molecular mechanisms, cross-talk, and relevance in targeted cancer therapy.

Keywords: cancer signaling, oncogenic pathways, PI3K/AKT, MAPK, Wnt, targeted therapy

1. Introduction

Cell signaling pathways constitute the fundamental biological circuitry that governs the life, function, and death of every cell within an organism. These complex networks of molecular interactions are responsible for processing and integrating a vast array of external and internal cues, thereby regulating critical cellular processes [1-5]. These include the precise coordination of cell cycle progression for controlled growth and division, the programmed execution of apoptosis to eliminate damaged or unnecessary cells, the intricate programs of cellular differentiation that establish specialized tissue functions, and the finely tuned immune responses that protect against pathogens and maintain tissue integrity. Under normal physiological conditions, these pathways operate in a tightly regulated equilibrium, ensuring cellular homeostasis and proper tissue architecture. However, the pathogenesis of cancer is fundamentally rooted in the subversion of this exquisite regulation. Through a combination of genetic alterations—such as somatic mutations, gene amplifications, and chromosomal rearrangements—and epigenetic modifications that alter gene expression without changing the DNA sequence, these critical signaling networks are systematically corrupted. These disruptions typically result in the constitutive activation of growth-promoting (oncogenic) pathways and/or the functional inactivation of growth-restraining (tumor-suppressive) pathways. The consequence is a malignant cellular transformation, characterized by the acquisition of the hallmarks of cancer: uncontrolled proliferation, evasion of cell death, sustained angiogenesis, tissue invasion, and metastasis [1-3]. 

Over the past several decades, the painstaking elucidation of these dysregulated cancer signaling networks has been transformative for the field of oncology. Mapping the specific oncogenic drivers within a patient’s tumor has shifted the therapeutic paradigm from broadly cytotoxic agents to targeted therapies. These drugs—including monoclonal antibodies and small-molecule kinase inhibitors—are designed to specifically block the activity of mutated or overactive proteins within these corrupted pathways. This foundational knowledge directly underpins the modern era of precision oncology, an approach that tailors treatment decisions to the unique molecular profile of an individual’s cancer. The continued decoding of signaling complexity, pathway crosstalk, and adaptive resistance mechanisms remains paramount for developing more effective, durable, and personalized cancer treatments [5-13].

2. PI3K/AKT/mTOR pathway

The phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway is one of the most critical and frequently dysregulated signaling networks in human cancer, governing a vast array of cellular processes essential for growth and survival. This pathway is typically activated downstream of receptor tyrosine kinases (RTKs) or G-protein coupled receptors. Upon activation, PI3K phosphorylates the lipid PIP2 to generate PIP3, which serves as a docking site for AKT at the plasma membrane. AKT is subsequently phosphorylated and activated, triggering a cascade that promotes cell survival by inhibiting pro-apoptotic proteins like BAD, enhances glucose metabolism to fuel rapid proliferation, and stimulates protein synthesis via mTOR complex 1 (mTORC1). Oncogenic activation of this pathway is extraordinarily common, occurring through multiple mechanisms including gain-of-function mutations in PIK3CA (the gene encoding the catalytic subunit of PI3K), which lead to constitutive lipid kinase activity; loss-of-function mutations or deletions of the tumor suppressor PTEN, a phosphatase that degrades PIP3 and thus acts as the pathway’s primary negative regulator; and amplification or hyperactivation of AKT isoforms. These alterations are pervasive across a wide spectrum of malignancies, from breast, endometrial, and prostate cancers to glioblastomas and various hematological malignancies. The centrality of this pathway to cancer cell biology has made it a major therapeutic target, leading to the development of numerous inhibitors targeting PI3K, AKT, and mTOR, though clinical success is often tempered by pathway redundancy, feedback loops, and off-target toxicities [3-18].

Figure 1. Major cancer signaling pathways. It presents a clean, white-background schematic with a central circle labeled Cancer Hallmarks (proliferation, apoptosis resistance, angiogenesis, metastasis), surrounded by color-coded modules for the PI3K/AKT/mTOR, MAPK/ERK, JAK/STAT, NF‑κB, Wnt/β‑catenin, and p53 pathways. Each pathway is illustrated with arrows showing activation or inhibition relationships, making it visually clear and publication‑ready.

3. MAPK (RAS/RAF/MEK/ERK) pathway

The mitogen-activated protein kinase (MAPK) pathway, often referred to as the RAS/RAF/MEK/ERK cascade, is a fundamental conduit for transmitting extracellular mitogenic signals—from growth factors, hormones, and cytokines—to the nucleus to regulate gene expression and drive cell division. The pathway is sequentially activated: a signal from an RTK leads to the activation of membrane-bound RAS (KRAS, NRAS, HRAS), which recruits and activates RAF kinases (ARAF, BRAF, CRAF). RAF then phosphorylates and activates MEK1/2, which in turn phosphorylates and activates ERK1/2. Activated ERK translocates to the nucleus to phosphorylate transcription factors like ELK1 and c-MYC, promoting the expression of genes involved in the cell cycle. Oncogenic deregulation most commonly occurs through activating mutations in RAS genes, particularly KRAS, which lock the protein in a GTP-bound, constitutively active state, and through mutations in BRAF (most notably the V600E mutation), which result in hyperactive kinase activity independent of upstream RAS signaling. This leads to a continuous, ligand-independent signal that drives uncontrolled cellular proliferation and survival. The MAPK pathway is of paramount clinical importance in several cancers, including melanoma (where BRAF V600E mutations are prevalent), colorectal carcinoma (often driven by KRAS mutations), and non-small cell lung cancer. The development of targeted BRAF and MEK inhibitors has revolutionized the treatment of BRAF-mutant melanoma, although resistance through pathway reactivation or alternative signaling rapidly emerges, underscoring the need for combination strategies [3-18]. 

4. Wnt/β-catenin signaling

The Wnt/β-catenin signaling pathway is an ancient and evolutionarily conserved system that plays a non-negotiable role in embryonic development, tissue homeostasis, and stem cell maintenance by regulating cell fate decisions, polarity, and self-renewal. In the canonical Wnt pathway, in the absence of a Wnt ligand, a “destruction complex”—comprising the tumor suppressor adenomatous polyposis coli (APC), Axin, casein kinase 1 (CK1), and glycogen synthase kinase-3β (GSK-3β)—phosphorylates β-catenin, targeting it for ubiquitination and proteasomal degradation. When a Wnt ligand binds to its Frizzled receptor and LRP co-receptor, this destruction complex is inhibited. This allows β-catenin to accumulate in the cytoplasm and translocate to the nucleus, where it partners with TCF/LEF transcription factors to activate target genes such as MYC and CCND1 (cyclin D1). In cancer, this pathway is hijacked primarily through mutations that lead to the aberrant stabilization and nuclear accumulation of β-catenin. The most common mechanisms are inactivating mutations in the APC gene, which cripple the destruction complex, and gain-of-function mutations in CTNNB1 (the gene encoding β-catenin) that prevent its phosphorylation and degradation. This constitutive activation drives tumor initiation and progression by promoting a stem-like, proliferative state and  inhibiting differentiation. Wnt/β-catenin dysregulation is a hallmark of colorectal cancer (where over 80% of cases involve APC mutations), hepatocellular carcinoma, and other malignancies. Its central role in cancer stem cells makes it a compelling but challenging therapeutic target, as direct inhibition risks severe toxicity to normal stem cell compartments [1-3,9].

5. JAK/STAT pathway

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is a principal signaling module for a wide array of cytokines, interleukins, and growth factors, linking extracellular signals directly to transcriptional programs in the nucleus. The canonical signaling cascade involves ligand binding to cytokine receptors, which induces receptor dimerization and the activation of associated JAK kinases. Activated JAKs phosphorylate the receptor, creating docking sites for latent cytoplasmic STAT proteins. Upon recruitment, STATs are phosphorylated by JAKs, leading to their dimerization, nuclear translocation, and binding to specific DNA sequences to regulate target gene expression. In oncology, persistent activation of this pathway, particularly of STAT3 and STAT5, is a common driver of malignancy. Constitutive activation can arise from autocrine or paracrine cytokine loops, gain-of-function mutations in JAK genes (e.g., JAK2 V617F in myeloproliferative neoplasms), or hyperactivation of upstream oncogenes like EGFR or BCR-ABL. Activated STATs contribute to oncogenesis by promoting cell proliferation and survival (through targets like BCL2 and MCL1), facilitating immune evasion by suppressing anti-tumor immune responses, and sustaining a pro-tumorigenic inflammatory microenvironment [3,11-14]. The JAK/STAT pathway is thus a critical nexus linking inflammation to cancer, playing significant roles in hematologic cancers, breast cancer, and head and neck squamous cell carcinoma. JAK inhibitors are used clinically for certain myeloproliferative disorders, and targeting STATs directly remains an active area of investigation to disrupt this key survival and immune-modulatory axis.

6. NF-κB signaling

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway is a master regulator of the immune and inflammatory response, cell survival, and proliferation. In its inactive state, NF-κB dimers (commonly p50/p65) are sequestered in the cytoplasm by inhibitory proteins of the IκB family [13-14]. A diverse array of stimuli—including pro-inflammatory cytokines (TNF-α, IL-1), pathogen-associated molecular patterns (PAMPs), and cellular stress—activate the IκB kinase (IKK) complex. IKK phosphorylates IκB proteins, marking them for ubiquitination and proteasomal degradation, thereby releasing NF-κB to translocate to the nucleus and activate the transcription of hundreds of target genes. In cancer, chronic or constitutive activation of NF-κB is a frequent occurrence, driven by persistent inflammatory stimuli, mutations in pathway components (e.g., in MYD88 or CARD11), or activation by oncogenic signals from pathways like RAS or EGFR. This activation confers a powerful survival advantage to tumor cells by upregulating anti-apoptotic genes (e.g., BCL2, XIAP), promotes angiogenesis via VEGF, enhances invasion and metastasis through the induction of matrix metalloproteinases (MMPs) and EMT regulators, and shapes an immunosuppressive tumor microenvironment. Consequently, NF-κB is a central player in inflammation-associated cancers, such as those linked to chronic infection (e.g., hepatitis-induced hepatocellular carcinoma, H. pylori-induced gastric cancer) or inflammatory bowel disease (colorectal cancer). Its pleiotropic roles make NF-κB a challenging but highly significant therapeutic target for disrupting the interplay between inflammation and malignancy.

7. TGF-β signaling

The transforming growth factor-beta (TGF-β) pathway exemplifies a quintessential “double-edged sword” in cancer biology, exhibiting starkly context-dependent roles as both a potent tumor suppressor in pre-malignant and early-stage lesions and a pro-metastatic driver in advanced disease. In normal epithelial cells and early tumorigenesis, TGF-β signaling acts as a powerful growth inhibitor. It signals through serine/threonine kinase receptors that phosphorylate SMAD proteins (SMAD2/3), which then complex with SMAD4, translocate to the nucleus, and activate genes that induce cell cycle arrest (via CDK inhibitors like p21) and apoptosis. Loss of this tumor-suppressive response, through mutations in receptors or SMADs (notably SMAD4), is a common step in cancer progression. Paradoxically, in advanced cancers that have escaped this growth-inhibitory arm, the same TGF-β pathway is co-opted to promote aggression. It drives the epithelial–mesenchymal transition (EMT), a process that enhances cell motility, invasion, and stemness by downregulating epithelial markers (e.g., E-cadherin) and upregulating mesenchymal markers (e.g., vimentin) [13-25]. Furthermore, TGF-β exerts profound immunosuppressive effects on the tumor microenvironment by inhibiting cytotoxic T-cell and natural killer cell function while promoting the activity of regulatory T cells and myeloid-derived suppressor cells. It also stimulates fibroblasts to become tumor-promoting cancer-associated fibroblasts (CAFs) and enhances the production of extracellular matrix, facilitating metastasis. This functional switch makes targeting the TGF-β pathway complex, as therapeutic strategies must aim to inhibit its oncogenic functions in late-stage disease without impairing its residual tumor-suppressive roles in normal tissues.

8. Notch and hedgehog pathways

The Notch and Hedgehog pathways represent a class of signaling cascades whose primary physiological roles are in embryonic development and adult tissue homeostasis, making their dysregulation in cancer particularly consequential. The Notch signaling pathway functions as a fundamental communication system for cell fate decisions. Operating through direct cell-to-cell contact, it is pivotal for controlling differentiation, maintaining stem cell populations in regenerative tissues, and regulating processes like angiogenesis. When abnormally activated in cancer—through mechanisms such as gene amplification, activating mutations, or persistent ligand exposure—Notch signaling can enforce a stem-like, undifferentiated state within tumor cells. This contributes directly to tumor initiation, progression, and the maintenance of a therapy-resistant cancer stem cell (CSC) pool. Similarly, the Hedgehog (Hh) signaling pathway is a master regulator of tissue patterning and cell proliferation during development. In adults, it is largely quiescent but can be reactivated in malignancy. Aberrant Hh signaling, often driven by mutations in pathway components like PTCH1 or SMO, or through ligand overproduction, promotes tumor growth by stimulating cancer cell proliferation, supporting a stem cell niche, and facilitating interactions with the tumor microenvironment that foster survival [17-18]. The dysregulation of these developmental pathways underscores a critical theme in oncology: cancers frequently hijack the body’s own tools for growth and repair. Their activation contributes not only to tumorigenesis but also to formidable therapeutic resistance, as the same stem-like properties they confer can allow tumor cells to survive conventional chemotherapy and radiotherapy, leading to relapse and metastatic spread. Consequently, these pathways are high-priority targets for developing drugs aimed at eradicating the resilient CSC population.

9. p53 and cell cycle pathways

The p53 protein, encoded by the TP53 gene, stands as the most critical tumor suppressor in the human genome, functioning as the central coordinator of the cellular response to stress. Often termed the “guardian of the genome,” p53 is activated by a wide array of insults, including DNA damage, oncogene activation, and hypoxia. Upon activation, it acts primarily as a transcription factor to initiate programs for cell cycle arrest, enabling DNA repair; cellular senescence, a permanent exit from the cell cycle; or apoptosis (programmed cell death), eliminating severely damaged cells. This exquisite control over cell fate makes p53 the principal barrier against the propagation of cells with genomic instability [20-21]. The profound importance of p53 is starkly highlighted by its mutation frequency, with alterations in the TP53 gene occurring in over 50% of all human cancers across virtually every tumor type. These mutations are predominantly missense changes that not only cause a loss of function, crippling its tumor-suppressive abilities, but also often confer a dominant-negative effect over any remaining wild-type p53 and can even lead to gain-of-function oncogenic properties. The consequence is a catastrophic breakdown in cellular integrity: cells lose their primary checkpoint controls, continue to divide despite carrying DNA damage, and accumulate mutations at an accelerated rate. This erosion of genomic stability is a fundamental enabling characteristic of cancer, driving tumor heterogeneity, evolution, and aggressiveness. Therapeutic strategies to restore p53 function or to exploit the specific vulnerabilities of p53-deficient cells, such as synthetic lethality, remain a major focus of oncology research.

10. Hippo pathway

The Hippo pathway is an evolutionarily conserved kinase cascade that functions as a master regulator of organ size and tissue homeostasis by precisely balancing cell proliferation with apoptosis. In healthy tissues, an active Hippo signaling pathway, through a core kinase module (MST1/2 and LATS1/2), phosphorylates and inhibits the downstream transcriptional co-activators YAP (Yes-associated protein) and TAZ (Transcriptional co-activator with PDZ-binding motif), sequestering them in the cytoplasm and targeting them for degradation. This keeps growth in check. In cancer, this regulatory brake is frequently released through various mechanisms, including genetic mutations in upstream regulators (e.g., NF2), loss of cell polarity, or increased mechanical stress from a stiffening tumor microenvironment. This inactivation of the Hippo pathway leads to the nuclear accumulation and hyperactivation of YAP/TAZ. Once in the nucleus, YAP/TAZ partner with transcription factors like TEAD to drive the expression of a potent pro-growth genetic program [23-35]. This program promotes uncontrolled cell proliferation and survival, induces epithelial-to-mesenchymal transition (EMT) to enhance invasiveness, and supports metastasis. Furthermore, YAP/TAZ activation is instrumental in maintaining cancer stem cell properties and in remodeling the tumor microenvironment to favor cancer progression. Notably, the Hippo pathway integrates signals from cell-cell contact, mechanical cues, and other oncogenic pathways, positioning YAP/TAZ as central hubs for sensing and responding to the physical and biochemical landscape of the tumor. Its frequent dysregulation across diverse cancer types makes the Hippo/YAP/TAZ axis a compelling target for novel therapeutic interventions aimed at curbing tumor overgrowth and metastatic potential.

11. Pathway crosstalk and therapeutic targeting

Cancer signaling pathways do not function as isolated linear cascades but as components of a highly interconnected and dynamic network. This web of molecular interactions, often termed pathway crosstalk, creates a robust signaling ecosystem that allows tumors to maintain growth signals, adapt to stress, and evade targeted therapies. Understanding these connections is critical for overcoming therapeutic resistance [1-11].

The crosstalk between major pathways such as PI3K/AKT/mTOR, RAS/MAPK/ERK, and Wnt/β-catenin is a prime example of this complexity [5-19]. These pathways engage in extensive reciprocal regulation through multiple mechanisms:

  • Direct molecular interactions: Key nodes in one pathway can directly phosphorylate or regulate components of another. For instance, active ERK from the MAPK pathway can phosphorylate and inhibit TSC2, a negative regulator of mTOR, thereby hyperactivating the PI3K/AKT pathway.
  • Shared downstream effectors: Pathways often converge on common downstream effectors like MYC, cyclin D1, or GSK3β, allowing integrated control over cell cycle progression and survival.
  • Feedback and feedforward loops: Pathway activation frequently triggers compensatory feedback. A classic example is the negative feedback in the MAPK pathway, where ERK phosphorylates upstream receptors and adaptors to dampen signaling. Inhibition of one node (e.g., mTOR) can relieve this feedback, leading to paradoxical activation of a parallel pathway (e.g., MAPK or PI3K via RTK upregulation), thereby sustaining survival signals.

This intricate crosstalk is a primary driver of intrinsic and acquired drug resistance. Monotherapy targeting a single pathway (e.g., a BRAF inhibitor in melanoma or an EGFR inhibitor in lung cancer) often leads to rapid tumor adaptation. Resistance mechanisms frequently involve the reactivation of the targeted pathway through secondary mutations or the compensatory activation of a parallel pathway that fulfills the same oncogenic need, a process known as pathway bypass.

Consequently, the therapeutic paradigm is shifting from single-agent targeting to rational combination strategies and systems-based approaches. Effective therapeutic design must consider the network state of a tumor [32-40]. This involves:

  1. Vertical and Horizontal Combinations: Combining inhibitors that target different nodes within the same pathway (vertical) or key nodes in two compensatory pathways (horizontal). For example, combining a BRAF inhibitor with a MEK inhibitor in melanoma, or an EGFR inhibitor with a MET inhibitor in lung cancer.
  2. Adaptive Therapy and Sequential Targeting: Designing treatment schedules that anticipate and preempt evolutionary escape routes, using pharmacodynamic biomarkers to guide therapy switching.
  3. Network Pharmacology and Polypharmacology: Developing single agents (polypharmacology) or drug cocktails (network pharmacology) that simultaneously modulate multiple critical nodes in the cancer signaling network to induce a more profound and durable response.

Ultimately, overcoming the challenge of pathway crosstalk requires moving beyond a “one gene, one drug” model. The future of precision oncology lies in combinatorial therapeutic strategies informed by a deep understanding of the tumor’s unique signaling network architecture, enabled by systems biology and real-time molecular monitoring.

12. Conclusion

The intricate network of major cancer signaling pathways—including the PI3K/AKT, RAS/MAPK, Wnt/β-catenin, JAK/STAT, NF-κB, TGF-β, Notch, Hedgehog, p53, Hippo, and Receptor Tyrosine Kinase cascades—collectively form the molecular symphony that orchestrates every critical facet of oncogenesis. These pathways do not operate in isolation but engage in a dynamic and often context-dependent crosstalk, creating a complex signaling ecosystem that governs fundamental cellular processes. They dictate the core hallmarks of cancer, from sustaining proliferative signaling and evading growth suppressors to resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Furthermore, their interactions with the tumor microenvironment and immune system underscore their role in shaping tumor immunogenicity and therapy resistance.

Significant advances in our understanding have moved beyond the linear characterization of individual pathways to reveal their multidimensional interactions, feedback loops, and compensatory mechanisms. The elucidation of regulatory mechanisms—such as post-translational modifications, spatial regulation within cellular compartments, and non-canonical signaling branches—has provided a more nuanced view of pathway dysregulation. This deeper knowledge is fundamentally shaping the landscape of targeted and personalized cancer treatment. Modern therapeutic strategies increasingly focus on combinatorial approaches that simultaneously inhibit multiple synergistic pathways, employ synthetic lethal interactions to target specific genetic vulnerabilities, and utilize biomarker-driven patient selection to maximize efficacy. The integration of high-throughput genomics, proteomics, and computational modeling continues to identify novel targets and resistance mechanisms, pushing the frontier toward more precise and adaptive therapies. Ultimately, the continued dissection of this complex signaling web remains paramount for developing the next generation of interventions capable of outmaneuvering cancer’s adaptive resilience and improving patient outcomes.

Author Contributions: Conceptualisation, M.Y.R.; software, M.Y.R.; investigation, M.Y.R.;  writing—original draft preparation, M.Y.R.; writing—review and editing, M.Y.R.; visualisation, M.Y.R.; supervision, M.Y.R.; project administration, M.Y.R. The author has read and agreed to the published version of the manuscript.

Funding: Not applicable.

Acknowledgments: We are grateful to the Department of Biochemistry, College of Science, University of Jeddah, Jeddah-21589 Saudi Arabia for providing us all the facilities to carry out the entire work.

Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.

Data Availability Statement: All the related data are supplied in this work or have been referenced properly.

References

  1. Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011;144(5):646–674. doi:10.1016/j.cell.2011.02.013
  2. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer Genome Landscapes. Science. 2013;339(6127):1546–1558. doi:10.1126/science.1235122
  3. Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017;169(3):381–405. doi:10.1016/j.cell.2017.04.001
  4. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase–AKT pathway in human cancer. Nat Rev Cancer. 2002;2(7):489–501. doi:10.1038/nrc839
  5. Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol. 2010;28(6):1075–1083. doi:10.1200/JCO.2009.25.3641
  6. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3(1):11–22. doi:10.1038/nrc969
  7. Samatar AA, Poulikakos PI. Targeting RAS–ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov. 2014;13(12):928–942. doi:10.1038/nrd4281
  8. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–3290. doi:10.1038/sj.onc.1210421
  9. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–1205. doi:10.1016/j.cell.2012.05.012
  10. Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14(15):1837–1851. doi:10.1101/gad.14.15.1837
  11. Yu H, Lee H, Herrmann A, Buettner R, Jove R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer. 2014;14(11):736–746. doi:10.1038/nrc3818
  12. Bromberg J. Stat proteins and oncogenesis. J Clin Invest. 2002;109(9):1139–1142. doi:10.1172/JCI0215671
  13. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18(5):309–324. doi:10.1038/nri.2017.142
  14. Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013;12:86. doi:10.1186/1476-4598-12-86
  15. Massagué J. TGFβ in Cancer. Cell. 2008;134(2):215–230. doi:10.1016/j.cell.2008.07.001
  16. Ikushima H, Miyazono K. TGFβ signalling: a complex web in cancer progression. Nat Rev Cancer. 2010;10(6):415–424. doi:10.1038/nrc2853
  17. Bray SJ. Notch signalling in context. Nat Rev Mol Cell Biol. 2016;17(11):722–735. doi:10.1038/nrm.2016.94
  18. Ranganathan P, Weaver KL, Capobianco AJ. Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer. 2011;11(5):338–351. doi:10.1038/nrc3035
  19. Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059–3087. doi:10.1101/gad.938601
  20. Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol. 2007;8(4):275–283. doi:10.1038/nrm2147
  21. Levine AJ. p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer. 2020;20(8):471–480. doi:10.1038/s41568-020-0262-1
  22. Sherr CJ. Principles of tumor suppression. Cell. 2004;116(2):235–246. doi:10.1016/S0092-8674(03)01075-4
  23. Yu FX, Guan KL. The Hippo pathway: regulators and regulations. Genes Dev. 2013;27(4):355–371. doi:10.1101/gad.210773.112
  24. Zanconato F, Cordenonsi M, Piccolo S. YAP/TAZ at the Roots of Cancer. Cancer Cell. 2016;29(6):783–803. doi:10.1016/j.ccell.2016.05.005
  25. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–1134. doi:10.1016/j.cell.2010.06.011
  26. Baselga J. Targeting tyrosine kinases in cancer: the second wave. Science. 2006;312(5777):1175–1178. doi:10.1126/science.1125951
  27. O’Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66(3):1500–1508. doi:10.1158/0008-5472.CAN-05-2925
  28. Duncan JS, Whittle MC, Nakamura K, et al. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell. 2012;149(2):307–321. doi:10.1016/j.cell.2012.02.053
  29. Dancey JE, Chen HX. Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat Rev Drug Discov. 2006;5(8):649–659. doi:10.1038/nrd2089
  30. Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153–183. doi:10.1210/edrv.22.2.0428
  31. Katoh M, Katoh M. Molecular genetics and targeted therapy of WNT-related human diseases (Review). Int J Mol Med. 2017;40(3):587–606. doi:10.3892/ijmm.2017.3071
  32. Yu FX, Zhao B, Guan KL. Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell. 2015;163(4):811–828. doi:10.1016/j.cell.2015.10.044
  33. Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017;169(6):985–999. doi:10.1016/j.cell.2017.05.016
  34. Karin M. Nuclear factor-κB in cancer development and progression. Nature. 2006;441(7092):431–436. doi:10.1038/nature04870
  35. Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell. 2018;173(2):321–337.e10. doi:10.1016/j.cell.2018.03.035
  36. Garraway LA, Jänne PA. Circumventing cancer drug resistance in the era of personalized medicine. Cancer Discov. 2012;2(3):214–226. doi:10.1158/2159-8290.CD-12-0012
  37. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446–454. doi:10.1038/nature25183
  38. Ashworth A, Lord CJ. Synthetic lethal therapies for cancer: what’s next after PARP inhibitors?. Nat Rev Clin Oncol. 2018;15(9):564–576. doi:10.1038/s41571-018-0055-6
  39. Huang S, Chaudhary K, Garmire LX. More Is Better: Recent Progress in Multi-Omics Data Integration Methods. Front Genet. 2017;8:84. doi:10.3389/fgene.2017.00084
  40. Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature. 2019;575(7782):299–309. doi:10.1038/s41586-019-1730-1

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of Global Journal of Basic Science and/or the editor(s). Global Journal of Basic Science and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. 

Copyright: © 2025 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Loading

Bibliography