Even though oncology has been a recognized subspecialty of internal medicine for 40 years, the past decade has seen more advances in the fight against cancer than ever before.
“What has been remarkable in the proliferation of cancer treatment since 2000 is not just the number of new drugs approved to fight cancer,” said Khaleel Ashraf, MD, a medical oncologist with Hematology-Oncology Associates of Alabama, “but also the large number of previously unknown pathways that are being exploited.”
“Few, if any, of these can be called a magic bullet against cancer,” Ashraf said. “But despite the fact that most cancers are very complex, combination and sequential use of these agents has resulted in meaningful survival improvements while maintaining quality of life, including in certain previously chemo-resistant cancers.”
The first and best example of molecular targeted therapy, said Ashraf, is the development of the Bcr-Abl tyrosine kinase inhibitor imatinib (Gleevec) for the treatment of chronic myelocytic leukemia. The drug’s clinical and commercial success provided proof of principle for the therapeutic power of targeting specific molecular pathways in cancer, prompting large amounts of funding for the development of targeted medications since 2000.
“The adage ‘Know your enemy’ is very apt in cancer therapy,” Ashraf said. “The more we know about it at a molecular level, the better we can customize treatment.
“Molecular data also provides clinically relevant prognostic information. With increased screening, we are finding more early stage cancers, and molecular prognostic scoring helps clinicians make patient- and tumor-specific recommendations regarding adjuvant therapy.”
“But one of the challenges is that payers have yet to catch up to these advances,” Ashraf said. “And even if a treatable target with an approved drug is available, it is sometimes not possible to prescribe that drug since drugs are still approved based on specific cancer locations and not for individual mutations.”
Ashraf also noted that various markers are now either available or in the developmental stages that can predict with some degree of accuracy a particular patient’s cancer cell’s response to certain chemotherapeutic agents. A molecular analysis of the tumor can help the oncologist formulate a treatment plan tailored to the patient’s cancer.
A promising new approach to cancer treatment is the use of drug therapy that exploits the body’s own immune system to attack cancer.
“One way is to interfere with the cancer cell’s ability to ‘hide’ from immune cells,” Ashraf said. “For example, Lambrolizumab, which is now in development, acts by disrupting the immune check point protein PD-1 expressed by several cancer cells including melanoma cells. This makes those cells susceptible for immune mediated cell kill.”
Another approach currently in the development stages is the use of customizable vaccines that use a patient’s tumor cells to get the body’s immune system to attack a variety of solid and hematological cancers.
The goal of this and other newer cancer treatments is to focus anti-cancer activity on a tumor while sparing healthy tissues. The traditional chemotherapy approach of “carpet bombing” comes at a price as it targets not just cancer cells; it also negatively affects normal cells.
“Many of the advances in surgical oncology and radiation oncology have made this goal a reality with regard to the local treatment of tumors,” Ashraf said. “From a systemic therapy perspective, packaging chemotherapy drugs or radioactive material with a cancer cell-specific antibody can achieve this same goal of targeting cancer cells while sparing other organs.”
With these newer agents, however, come a completely different set of toxicities than with traditional chemotherapy, ranging from minor skin rashes to life threatening issues like interstitial lung disease or immunological and cytokine storm. Early recognition and treatment of these side effects are an integral component of patient management.
“One of the practical challenges to using the newer cancer drugs is the need for very detailed and molecular level information before prescribing them. These drugs often do not work unless a specific target is present in the tumor, and it is critical to use these drugs only in the appropriate patients,” Ashraf said. “In fact, there are occasions where a targeted drug, when given to a patient without the specific target, can promote tumor growth instead of suppression, as in the case of BRAF inhibitor for melanoma.
“Several other challenges remain, including the often prohibitive cost of many of these newer medications. But as more of these drugs become generic, prices should drop.”
As far as future developments in cancer treatment, Ashraf believes the news will only get better.
“While the advances in the last decade or so have been remarkable, they will likely pale in comparison to what is expected in the next 10 years,” he said. “With large scale efforts like the Cancer Genome Atlas project, an incredible amount of new data on the molecular pathogenesis of cancers is being unmasked.”
