Smart drugs block a specific molecule a cancer depends on, as daily tablets or antibody drips, and they work only when a tumor test finds the target. Imatinib left 83.3 percent of leukemia patients alive at ten years, and in selected solid tumors smart drugs beat chemotherapy. We explain testing, side effects, resistance and the trip.
About This Department
Medical Oncology
A smart drug is only as smart as the test behind it. With the right target it can turn a fatal cancer into a manageable one.
People call targeted therapy smart drugs. These medicines block a specific molecule a cancer depends on instead of attacking every dividing cell. They come as daily tablets or as antibody drips, and they work only in tumors that carry their target. The first of them showed what is possible. Among patients with chronic myeloid leukemia who started imatinib, 83.3 percent were alive ten years later, in a disease that had killed the majority within a few years. In solid tumors the gains are smaller but real, and every one of them starts with a test on the tumor.
83.3%
Alive at 10 years on imatinib for chronic myeloid leukemia, NEJM 2017
48% vs 5%
Tumor response with vemurafenib against chemotherapy, BRAF melanoma, NEJM 2011
74% vs 45%
Response with crizotinib against chemotherapy, ALK lung cancer, NEJM 2014
Free
Oncologist review of your pathology and gene tests
Free consultation
Send the pathology report with every marker result it lists, any gene sequencing report, the latest scans and the treatment history. A medical oncologist tells you whether your tumor has been tested for the targets that matter in your cancer, whether an approved smart drug fits, and what it would involve. The review is free and asks nothing of you in return.
Patients say smart drugs and oncologists say targeted therapy, so the title of this page, Smart Drugs For Cancer - Targeted Therapy, uses both. The name promises more than it delivers. Precision needs a target. This page explains how they work, how the target is found, what the landmark trials showed, what side effects to expect, why they stop working, and how a patient from abroad gets assessed in Istanbul and continue treatment at home.
How a smart drug works
1
The cancer depends on one signal
Some cancers grow because a single protein is stuck in the on position, through a mutation, a fusion or too many copies of a gene. The cancer comes to rely on that protein.
2
The drug blocks it
A targeted drug fits that protein, like a key in the wrong lock, and switches the signal off.
3
The cancer slows or shrinks
Cells that depended on the signal stop dividing or die. Healthy cells are largely spared.
Why smart is a misleading word
The drugs are not smart on their own. A targeted drug given to a tumor without its target does little or nothing, and sometimes does harm. What makes the treatment smart is the laboratory test that finds the target first, and the oncologist who reads the result correctly.
Tablets and drips
Two families, two ways of working
Targeted drugs fall into two families that reach their target in different ways. Their names give them away. Drugs ending in -nib are small molecules, and drugs ending in -mab are monoclonal antibodies.
Two families
Small molecules, taken as tablets
Small enough to enter the cell, these drugs block the enzyme inside it. Imatinib, osimertinib, crizotinib and the CDK4/6 inhibitors are examples, taken at home once or twice a day for as long as they keep working.
Monoclonal antibodies, given by drip
Too large to enter cells. Antibodies bind the target on the outside, block its signal or flag the cell for the immune system, and trastuzumab for HER2-positive breast cancer is the best known of them. Some carry a chemotherapy payload into the cell, the antibody drug conjugates.
The test comes first
From biopsy to report
1
The tissue
The tumor sample from the biopsy or operation, stored as a paraffin block. Sometimes a new biopsy or a blood test for tumor DNA is needed.
2
The test
Staining for single proteins such as HER2, or next-generation sequencing that reads hundreds of genes at once.
3
The report
A list of changes found, each graded by whether an approved drug, a trial or nothing matches it.
What European oncologists recommend
The European Society for Medical Oncology recommends routine sequencing of tumor samples in advanced non-squamous non-small cell lung cancer, prostate cancer, ovarian cancer and bile duct cancer, where large gene panels pay for themselves in treatment choices. In bowel cancer sequencing can replace single-gene tests. Outside these, a broad panel is reasonable if doctor and patient decide together and the patient understands that the chance of finding something useful is low. Mosele and colleagues, Annals of Oncology, 2020.
The drug that proved it
A leukemia that became a chronic condition
In the IRIS trial, patients with newly diagnosed chronic myeloid leukemia took imatinib, a tablet that blocks the BCR-ABL protein created by a chromosome swap. After a median of 10.9 years, 83.3 percent were alive and 82.8 percent had reached a complete response on chromosome testing. Serious side effects were uncommon and clustered in the first year. Hochhaus and colleagues, New England Journal of Medicine, 2017.
Targets and the drugs that hit them
Common targets
A handful of targets account for most smart drug use today.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
Common targets and examples of drugs
Target
Where it matters most
Example drugs
HER2
Breast and stomach cancer
Trastuzumab, pertuzumab, trastuzumab deruxtecan
EGFR
Lung cancer with an EGFR mutation
Osimertinib, gefitinib
ALK and ROS1
Lung cancer with a fusion
Alectinib, lorlatinib, crizotinib
BRAF V600E
Melanoma, thyroid, bowel and lung cancer
Dabrafenib with trametinib, encorafenib
BCR-ABL
Chronic myeloid leukemia
Imatinib, dasatinib, nilotinib
CDK4/6
Hormone receptor positive breast cancer
Palbociclib, ribociclib, abemaciclib
VEGF
Bowel, kidney, liver and other cancers
Bevacizumab, sunitinib, lenvatinib
NTRK fusions
Many rare cancers
Larotrectinib, entrectinib
When there is no target
Many tumors carry no change with a matching drug. The negative result still counts. It steers treatment toward chemotherapy, immunotherapy, surgery or radiotherapy, it saves the patient from months on a costly drug that would not have worked, and it stays in the file so that a new trial or a newly approved drug for that change can be matched against it later without testing the tissue again.
One target, several drugs
Newer drugs replace older ones for the same target when they work longer, reach the brain or cause fewer side effects. Crizotinib, the first ALK drug, has largely given way to alectinib and lorlatinib in first-line lung cancer. Progress comes fast. A drug that led in one year slips to second choice three years later.
Three trials in solid tumors
Three targets.
2001
HER2 breast cancer
Adding trastuzumab to chemotherapy in 469 women with HER2-positive metastatic breast cancer raised response from 32 to 50 percent and median survival from 20.3 to 25.1 months. Heart damage was the main risk, severe in 27 percent when given with an anthracycline, the reason the two are no longer combined. Slamon and colleagues, New England Journal of Medicine.
2011
BRAF melanoma
In 675 patients with BRAF V600E melanoma, vemurafenib raised survival at six months from 64 to 84 percent and response from 5 to 48 percent. Thirty-eight percent needed a dose change, and some developed new skin cancers. Chapman and colleagues, New England Journal of Medicine.
2014
ALK lung cancer
In 343 patients with untreated ALK-positive lung cancer, crizotinib gave a median time without progression of 10.9 against 7.0 months and response in 74 against 45 percent, with better quality of life. Solomon and colleagues, New England Journal of Medicine.
What these trials teach
Each drug beat chemotherapy only in patients selected by a test, and each came with its own side effects. None cured advanced disease. The gains were measured in months to years, and newer drugs for the same targets have since pushed them further.
Side effects
Each drug brings its own list.
Different from chemotherapy, and different from each other
Smart drugs spare most healthy cells but not all. Side effects follow the target. EGFR drugs cause an acne-like rash and diarrhea, while HER2 antibodies weaken the heart in some patients, so heart scans are repeated through treatment. BRAF drugs cause joint pain, sun sensitivity and new skin growths that a dermatologist checks every few months, and ALK drugs cause vision flashes, swelling of the ankles and bowel upset. VEGF drugs raise blood pressure and slow wound healing. Hair loss and nausea are less common than with chemotherapy, and a large share of patients keep working through treatment. The long course is the burden. A side effect that would be tolerable for three months can wear a patient down over three years, and dose adjustments are part of normal care.
Call the treating team the same day for breathlessness or a new cough, chest pain or palpitations, a spreading or blistering rash, severe diarrhea, yellow skin, or sudden changes in vision.
When a smart drug stops working
Resistance is expected
Why it happens
A cancer under pressure evolves. The target can mutate so the drug no longer fits, or the cancer switches to another growth signal and leaves the old one behind. In advanced solid tumors this happens sooner or later, within months to a few years for the large majority of patients.
What comes next
Test again. A new biopsy or a blood test for tumor DNA shows how the cancer escaped, and the result points to the next drug, whether a newer generation for the same target, a different targeted drug, or chemotherapy or immunotherapy.
Length of stay, flying, cost and the trip
Tablets or drips
Tablets
One week to start, then home
A first visit of five to seven days covers the consultation, any missing tests and the start of treatment. You can fly home once the plan is set, and the tablets continue at home with blood tests and scans that an oncologist there can arrange from the written plan.
Drips
Every one to four weeks
Antibodies are given in a day unit every one to four weeks, depending on the drug, so patients either return for each dose or continue with an oncologist at home. Our coordinator helps plan whichever suits the schedule.
Cost depends first on the drug, paid monthly or per dose for as long as it works, and on whether your own country covers it. Tests, scans and the day-unit time add to it. Published packages in Istanbul cover the consultation, tests, the first review, an interpreter and transfers, and leave out the hotel, flights and the drug supply. The review of your reports is free, and a written plan with figures follows. The coordinator writes in English, Arabic, French, Russian, Serbian, Romanian or Spanish, or arranges an interpreter, sends an appointment confirmation and an invitation letter naming the hospital and the treating doctor ten days before travel, and books the hotel and transfers. Two family members may join consultations, meals come in halal, vegetarian and diabetic versions, a prayer room is on site, and you may request a female doctor at first contact.
At home, and a caution
After you fly home
Follow-up
A plan your own doctor can follow
Once you are back home, your oncologist receives the written plan with the drug, dose, blood tests, heart or eye checks where needed and the scan schedule. The coordinator stays reachable on the same WhatsApp number, and clinical questions go to the oncologist who started the treatment.
Smart drugs without a matching test
Europe advises against it outside organized programs
Giving a targeted drug because a gene report lists a change, in a cancer where the drug is not approved, is tempting. The European Society for Medical Oncology recommends doing so only within an access program with a formal decision procedure, and a randomized French trial found no benefit from such off-label matching in heavily treated patients. A clinical trial is usually the better route.
Smart Drugs For Cancer - Targeted Therapy FAQ
What are smart drugs for cancer?
Smart drugs is the popular name for targeted therapy. These medicines block a specific molecule that the cancer depends on to grow, and they come in two forms. They include daily tablets such as imatinib and osimertinib and antibody drips such as trastuzumab.
Does everyone with cancer benefit from smart drugs?
No. They work only when the tumor carries the target, which a laboratory test must show. Many tumors carry no matching change, and for them other treatments remain the right choice.
Are smart drugs better than chemotherapy?
For the right patient, often yes. In selected patients vemurafenib raised response in melanoma from 5 to 48 percent and crizotinib raised it in ALK lung cancer from 45 to 74 percent against chemotherapy. Without the target, they offer little.
Do smart drugs have side effects?
Yes, but different ones. Rash, diarrhea, high blood pressure, heart effects, joint pain and vision changes depend on the drug. Hair loss and nausea are less common than with chemotherapy.
How long do smart drugs work?
In chronic myeloid leukemia, often for decades, with 83.3 percent alive at ten years on imatinib. In advanced solid tumors, typically months to a few years before resistance, when a new test guides the next drug.
Can I start smart drug treatment in Istanbul and continue at home?
Yes. A first visit of five to seven days covers testing and the start of treatment. Tablets continue at home, and drips can be given in Istanbul or by an oncologist at home following the written plan.
References
Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017;376(10):917-927.
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-92.
Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-16.
Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-77.
Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers, a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31(11):1491-1505.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Özcan YILDIZ, Medical Oncology.
