How Some Cancer Cells Avoid Self-Destruction
Some cancer cells survive by blocking their own self-destruct signals. Discover how this escape route is being targeted—and which drug and natural medicine research findings are strongest
Page 5 of the hub that unpacks the 2026 Cancer Stem Cells and Drug Resistance Review.
Some cancer cells survive by disabling their internal "self-destruct" system. Most cancer treatments do more than damage a cell: they rely on the damaged cell receiving the message that it is beyond repair and activating apoptosis, a carefully controlled form of cellular self-destruction.
How the Self-Destruct Signal Gets Blocked
Stem-like and treatment-resistant cancer cells may interfere with that message at several points. They can strengthen survival pathways such as PI3K/AKT/mTOR and NF-κB, increase anti-apoptotic proteins such as BCL-2, BCL-XL and MCL-1, alter mitochondrial signalling, or use autophagy—the recycling of damaged cell components—as a temporary survival strategy. The result is not that the treatment necessarily fails to reach the cell, but that the cell is better able to absorb the damage and remain alive.
Clinical Proof: Targeting Apoptosis
There is already an important clinical proof that this biology can be targeted in the right setting. Venetoclax (Venclexta) is a BH3-mimetic medicine that blocks the anti-apoptotic protein BCL-2, helping restore the death signal in certain blood cancers, especially chronic lymphocytic leukaemia and selected acute myeloid leukaemia settings.
It is not a universal cancer-stem-like-cell treatment, but it shows that a cancer's dependence on an anti-death protein can sometimes be turned into a treatment vulnerability. In AML, venetoclax is commonly used in combinations rather than alone because cancer cells may escape by increasing related survival proteins such as MCL-1 or BCL-XL. That is the same lesson found throughout CSC research: a resistant cancer cell rarely depends on only one escape route.
See our site's section where we unpack what we have been learning about: senesence
Curcumin: A Multi-Pathway Research Contender
To date the leading natural-compound research contender in this area is curcumin, a group of compounds from turmeric.
Across cell, organoid and animal models, curcumin has been reported to affect several of the survival networks discussed in this review at once—including NF-κB, PI3K/AKT/mTOR, BCL-2-family signalling, mitochondrial function and autophagy—and in some models to increase tumour-cell apoptosis or sensitivity to chemotherapy. This multi-pathway activity is why it receives so much attention in CSC and treatment-resistance research.
However, this is encouraging preclinical research not a proven treatment strategy. Much of the curcumin evidence comes from cells and animals, often using concentrations that may not be achievable in human tumour tissue after oral supplements.
Curcumin also has low and variable absorption, formulations differ substantially and laboratory "synergy" does not establish improved survival or tumour control in people. Early human combination studies are encouraging but they do not establish that curcumin eliminates CSCs, reverses treatment resistance in humans or should be added to a person's regimen without oncology review. Learn more about the most current use of bio-available Curcumin in Oncology in our Natural Medicines in Oncology hub.
A practical discussion to have: "Does my cancer have a known dependence on an anti-apoptosis or survival pathway—such as BCL-2, MCL-1, PI3K/AKT/mTOR or NF-κB—that is clinically actionable, either with an approved therapy or a suitable trial? If I am considering curcumin or another supplement, could it interact with my current treatment or change its intended effect?"
References and further reading
Clinical proof: targeting apoptosis
Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia DiNardo CD, et al. New England Journal of Medicine. 2020;383:617–629. https://www.nejm.org/doi/full/10.1056/NEJMoa2012971 Landmark phase III trial: azacitidine plus the BCL-2 inhibitor venetoclax improved remission and overall survival compared with azacitidine alone in older or medically unfit people with newly diagnosed AML.
VENCLEXTA® (venetoclax) Prescribing Information U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/208573s031lbl.pdf Authoritative prescribing information confirming venetoclax is a BCL-2 inhibitor used for CLL/SLL and, in combination regimens, selected newly diagnosed AML settings. It also documents important safety issues, including tumour-lysis syndrome and clinically significant drug interactions.
Concomitant Targeting of BCL2 with Venetoclax and MAPK Signaling in Acute Myeloid Leukemia Haematologica. 2020. https://haematologica.org/article/view/9288 Useful for explaining resistance: BCL-2 blockade may be bypassed through related survival signals, including MCL-1 stabilisation through MAPK signalling—supporting the need for rational combinations.
Curcumin: preclinical research
The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway Cancers. 2024;16(8):1554. https://pubmed.ncbi.nlm.nih.gov/38672636/ Review of preclinical research examining curcumin and PI3K/AKT-related cancer survival signalling. It is useful background for why curcumin is often discussed.
Curcumin Potentiates the Potent Antitumor Activity of ACNU Against Glioblastoma by Suppressing the PI3K/AKT and NF-κB/COX-2 Signaling Pathways International Journal of Oncology. 2017. https://pubmed.ncbi.nlm.nih.gov/29180881/ Cell-based glioblastoma study reporting enhanced apoptosis with curcumin plus ACNU. It is a mechanistic experiment, not a human trial and not evidence that the combination should be used clinically.
Combination Effect of Curcumin With Docetaxel on the PI3K/AKT/mTOR Pathway to Induce Autophagy and Apoptosis in Esophageal Squamous Cell Carcinoma Molecular Medicine Reports. 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC7847521/ Laboratory study showing that curcumin and docetaxel affected PI3K/AKT/mTOR signalling, autophagy and apoptosis in oesophageal squamous-cell-carcinoma cells. Importantly, it also illustrates why interpretation is difficult: autophagy may either support cancer-cell survival or contribute to cell death depending on context.
This information is for education only. It is not medical advice, diagnosis, or treatment. Please speak with a qualified clinician before making changes to care, medication, or supplement use.
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