Navigating Uncharted Waters: Could COVID-19 and/or Certain COVID-19 Vaccines Promote Malignancy?

Abstract

Cancer is a complex dynamic disease that involves different biological capabilities including sustaining proliferative signaling, evading tumor suppression and immune surveillance, resisting cell death, enabling replicative immortality, reprogramming energy metabolism, inducing angiogenesis, and activating invasion and metastasis. Underlying these capabilities are genome instability, which expedites their acquisition, and inflammation, which fosters their function/s. Additionally, cancer exhibits another dimension of complexity: a heterogeneous repertoire of infiltrating and resident host cells, secreted factors, and extracellular matrix, known as the tumor microenvironment, that through a dynamic and reciprocal relationship with cancer cells supports immortality, local invasion, and metastatic dissemination. This staggering intricacy calls for some caution when advising all people with cancer (or a previous history of cancer) to receive the COVID-19 primary vaccine series plus additional booster doses. Moreover, because these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, safety, and the risk of interactions with anticancer therapies, which could reduce the efficacy and/or safety of either medical treatment. After reviewing the available literature, we are particularly concerned that COVID-19 vaccination may predispose some (stable) oncologic patients and survivors to cancer progression, recurrence and/or metastasis. This hypothesis is based on biological plausibility (i.e., induction of lymphopenia and inflammation; downregulation of ACE2 expression; activation of oncogenic cascades; sequestration of tumor suppressor proteins; suppression of type I IFN responses; dysregulation of the G4-RNA-protein binding system; unsilencing of LINE-1 retrotransposons; etc.) together with growing anecdotal evidence and reports filed to Vaccine Adverse Effects Report System (VAERS) suggesting that some cancer patients experienced disease exacerbation or recurrence following COVID-19 vaccination. In light of the above, we encourage the medical and scientific community to urgently evaluate the impact of COVID-19 vaccination on cancer biology, adjusting public health recommendations accordingly.